Ch 15 - Fluid and Acid Balance

Chemical Buffer System

- A chemical buffer system is a mixture in a solution of two chemical compounds that minimize pH changes when either an acid or a base is added to or removed from the solution. - A buffer system consists of a pair of substances involved in a reversible reaction—one substance that can yield free H+ as the [H+] starts to fall and another that can bind with free H+ (thus removing it from solution) when [H+] starts to rise. - An important example of such a buffer system is the carbonic acid-bicarbonate (H2CO3:HCO3 -) buffer pair. - When a strong acid such as HCl is added to an unbuffered solution, all the dissociated H+ remains free in the solution. - In contrast, when HCl is added to a solution containing the H2CO3:HCO3 - buffer pair, the HCO3 - immediately bind with the free H+ to form H2CO3. - This weak H2CO3 dissociates only slightly compared to the marked reduction in pH that occurred when the buffer system was not present and the additional H+ remained unbound. - In the opposite case, when the pH of the solution starts to rise from the addition of base or loss of acid, the H+-yielding member of the buffer pair, H2CO3, releases H+ to minimize the rise in pH. ** The body has four buffer systems: (1) the H2CO3:HCO3 - buffer system (2) the protein buffer system (3) the hemoglobin buffer system (4) the phosphate buffer system. Each buffer system serves an important role

What occurs when ECF volume is reduced vs. expanded?

- A reduction in ECF volume causes a fall in arterial blood pressure by decreasing plasma volume. - Conversely, expanding ECF volume raises arterial blood pressure by increasing plasma volume.

Acids

- Acids are a special group of hydrogen-containing substances that dissociate, or separate, when in solution to liberate free H+ and anions. - Many other substances (for example, carbohydrates) also contain hydrogen, but they are not classified as acids because the hydrogen is tightly bound within their molecular structure and is never liberated as free H+. - A strong acid has a greater tendency to dissociate in solution than a weak acid does—that is, a greater percentage of a strong acid's molecules separate into free H+ and anions. - Hydrochloric acid (HCl) is an example of a strong acid; every HCl molecule dissociates into free H+ and chloride (Cl-) when dissolved in H2O. - With a weaker acid such as carbonic acid (H2CO3), only a portion of the molecules dissociates in solution into H+ and bicarbonate anions (HCO3 -). - The remaining H2CO3 molecules remain intact. - Because only free H+ contributes to the acidity of a solution, H2CO3 is a weaker acid than HCl because H2CO3 does not yield as many free H+ per number of acid molecules present in solution

H+ excretion in kidney

- Acids are continuously added to body fluids as a result of metabolic activities, yet the generated H+ must not be allowed to accumulate. - Although the body's buffer systems can resist changes in pH by removing H+ from solution, the persistent production of acidic metabolic products would eventually overwhelm the limits of this buffering capacity. - Therefore, the constantly generated H+ must ultimately be eliminated from the body. - The lungs can remove only CO2-generated H+ by eliminating CO2. - The task of eliminating H+ derived from sulfuric, phosphoric, lactic, and other acids rests with the kidneys. - Furthermore, the kidneys can eliminate extra H+ derived from CO2. - All of the filtered H+ is excreted because the kidney tubules are not able to reabsorb H+, but most excreted H+ enters the urine via secretion. - Recall that the filtration rate of H+ equals plasma [H+] times GFR. Because plasma [H+] is extremely low (less than in pure H2O except during extreme acidosis, when pH falls below 7.0), the filtration rate of H1 is likewise extremely low. - This minute amount of filtered H+ is excreted in the urine. - However, most excreted H+ gains entry into the tubular fluid by being actively secreted by the tubular cells from the peritubular capillary plasma into the tubular lumen. - The proximal, distal, and collecting tubules all secrete H+. - Because the kidneys normally excrete H+, urine is usually acidic, having an average pH of 6.0. - The H+ secretory process begins in the tubular cells with CO2 from three sources: CO2 diffused into the tubular cells from (1) plasma or (2) tubular fluid or (3) CO2 metabolically produced within the tubular cells. - Catalyzed by carbonic anhydrase within the tubular cells, CO2 and H2O form H+ and HCO3 2. To secrete H+, an energy-dependent carrier in the luminal membrane then transports H+ out of the cell into the tubular lumen. - The luminal-membrane carrier differs in different parts of the nephron.

Coupling of HCO3 - Reabsorption with H+ Secretion

- Bicarbonate is freely filtered, but because the luminal membranes of tubular cells are impermeable to filtered HCO3 -, it cannot diffuse into these cells. - Therefore, reabsorption of HCO3 - must occur indirectly. - We will use the Type A intercalated cell as an example. - H+ secreted into the tubular fluid combines with filtered HCO3 - to form H2CO3. - Under the influence of a form of carbonic anhydrase that is located on the surface of the luminal membrane, H2CO3 decomposes into CO2 and H2O within the filtrate. - Unlike HCO3 -, CO2 and H2O can easily penetrate tubular cell membranes. - Within the cells, CO2 and H2O, under the influence of intracellular carbonic anhydrase, form H+ and HCO3 -. - Because HCO3 - can permeate these tubular cells' basolateral membrane by means of the Cl- -HCO3 - antiporter, it diffuses out of the cells and into the peritubular capillary plasma. Meanwhile, the generated H+ is actively secreted. - Because the disappearance of a HCO3 - from the tubular fluid is coupled with the appearance of another HCO3 - in the plasma, a HCO3 - has, in effect, been "reabsorbed." - Even though the HCO3 - entering the plasma is not the same HCO3 - that was filtered, the net result is the same as if HCO3 - were directly reabsorbed

Role of Left Atrial Volume Receptors

- Although the major stimulus for vasopressin secretion and thirst is an increase in ECF osmolarity, the vasopressin-secreting cells and thirst center are both influenced to a moderate extent by changes in ECF volume (and therefore plasma volume) mediated by input from the left atrial volume receptors. - Located in the left atrium, these volume receptors respond to pressure-induced stretch caused by blood flowing through, which reflects the ECF volume—that is, they monitor the "fullness" of the vascular system. In contrast, the aortic arch and carotid sinus baroreceptors monitor the mean driving pressure in the vascular system. - In response to a major reduction in ECF volume (.7% loss of volume), and accordingly in arterial pressure, as during hemorrhage, the left atrial volume receptors reflexly stimulate both vasopressin secretion and thirst. (By comparison, a change as small as a 1% increase in ECF osmolarity triggers increased vasopressin secretion, and an increase in osmolarity of 2% or more produces a strong desire to drink, indicative of the greater influence of the hypothalamic osmoreceptors than the left atrial volume receptors in controlling vasopressin secretion and thirst.) - In the face of a marked reduction in ECF volume, the outpouring of vasopressin and the increased thirst lead to decreased urine output and increased fluid intake, respectively. - Furthermore, vasopressin, at the circulating levels elicited by a large decline in ECF volume and arterial pressure, exerts a potent vasoconstrictor (that is, a "vaso" "pressor") effect on arterioles. - Both by helping expand the ECF and plasma volume and by increasing total peripheral resistance, vasopressin helps relieve the low blood pressure that elicited vasopressin secretion. - Simultaneously, the low blood pressure is detected by the aortic arch and carotid sinus baroreceptors, which help raise the pressure by increasing sympathetic activity to the heart and blood vessels. - Furthermore, sympathetic activity also contributes to the sensation of thirst and increased vasopressin activity. - Conversely, vasopressin and thirst are both inhibited when ECF volume (and, accordingly, plasma volume) and arterial blood pressure are elevated. - The resultant suppression of H2O intake, coupled with elimination of excess ECF and plasma volume in the urine, helps restore blood pressure to normal. - Recall that low NaCl, low ECF volume, and low arterial blood pressure also reflexly increase aldosterone secretion via RAAS. - The resulting increase in Na+ reabsorption leads to osmotic retention of H2O, expansion of ECF volume, and an increase in arterial blood pressure. - Aldosterone-controlled Na+ reabsorption is the most important factor in regulating ECF volume, with the vasopressin and thirst mechanism playing only a supportive role.

Nonphysiological Influences on Fluid Intake

- Although the thirst mechanism exists to control H2O intake, fluid consumption by humans is often influenced more by habit and sociological factors than by the need to regulate H2O balance. - Thus, even though H2O intake is critical in maintaining fluid balance, it is not precisely controlled in humans, who err especially on the side of excess H2O consumption. - We usually drink when we are thirsty, but we often drink even when we are not thirsty because, for example, we are on a coffee break. - With H2O intake being inadequately controlled and indeed even contributing to H2O imbalances in the body, the primary factor involved in maintaining H2O balance is urinary output regulated by the kidneys. - Accordingly, vasopressin-controlled H2O reabsorption is of primary importance in regulating ECF osmolarity

Do lymph and transcellular fluid affect the body fluid balance?

- Although these fluids are extremely important functionally, they represent an insignificant fraction of total body H2O. - Furthermore, the transcellular compartment as a whole usually does not reflect changes in the body's fluid balance. - For example, cerebrospinal fluid does not decrease in volume when the body as a whole is experiencing a negative H2O balance. - This is not to say that these fluid volumes never change. - Localized changes in a particular transcellular fluid compartment can occur pathologically, but such a localized fluid disturbance does not affect the fluid balance of the body. - Therefore, the transcellular compartment can usually be ignored when dealing with problems of fluid balance. - The main exception to this generalization occurs when digestive juices are abnormally lost from the body during heavy vomiting or diarrhea, which can bring about a fluid imbalance.

Overview of Compensated Acid-Base Disorders

- An individual's acid-base status cannot be assessed on the basis of pH alone. - Uncompensated acid-base abnormalities can readily be distinguished on the basis of deviations of either [CO2] or [HCO3 -] from normal. - However, when compensation has been accomplished and pH is essentially normal, determinations of [CO2] and [HCO3 -] can reveal an acid-base disorder, but the type of disorder cannot be distinguished. - For example, in both compensated respiratory acidosis and compensated metabolic alkalosis, [CO2] and [HCO3 -] are both above normal. - With respiratory acidosis, the original problem is an abnormal increase in [CO2], and a compensatory increase in [HCO3 -] restores the [HCO3 -]/[CO2] ratio to 20/1. - Metabolic alkalosis, by contrast, is characterized by an abnormal increase in [HCO3 -] in the first place; then a compensatory rise in [CO2] restores the ratio to normal. - Similarly, compensated respiratory alkalosis and compensated metabolic acidosis share similar patterns of [CO2] and [HCO3 -]. - Respiratory alkalosis starts out with reduced [CO2], which is compensated by a reduction in [HCO3 -]. - With metabolic acidosis, [HCO3 -] falls below normal, followed by a compensatory decrease in [CO2]. - Thus, in compensated acid-base disorders, the original problem must be determined by clinical signs and symptoms other than deviations in [CO2] and [HCO3 -] from normal.

The Reversible Incorporation of a Plasma Constituent

- Another possible internal exchange between the pool and the rest of the body is reversible incorporation of a plasma constituent into a more complex molecular structure to serve a specific purpose. - For example, iron is incorporated into hemoglobin within the red blood cells but is released intact back into the body fluids when the red blood cells degenerate

Importance of Regulating ECF Osmolarity

- Any circumstance that results in a loss or gain of free H2O (that is, loss or gain of H2O that is not accompanied by comparable solute deficit or excess) leads to changes in ECF osmolarity. - If there is a deficit of free H2O in the ECF, the solutes become too concentrated and ECF osmolarity becomes abnormally high—that is, it becomes hypertonic - If there is excess free H2O in the ECF, the solutes become too dilute and ECF osmolarity becomes abnormally low—that is, it becomes hypotonic. - When ECF osmolarity changes with respect to ICF osmolarity, osmosis takes place, with H2O either leaving or entering the cells depending on whether the ECF is more concentrated or less concentrated, respectively, than the ICF. - The osmolarity of the ECF must therefore be regulated to prevent these undesirable shifts of H2O out of or into the cells. - As far as the ECF itself is concerned, the concentration of its solutes does not really matter. - However, it is crucial that ECF osmolarity be maintained within narrow limits to prevent the cells from shrinking (by osmotically losing water to the ECF) or swelling (by osmotically gaining fluid from the ECF).

Long-Term Control Measures to Maintain Blood Pressure

- In the long run, other compensatory measures come into play to restore ECF volume to normal. - Long-term regulation of blood pressure rests with the kidneys and the thirst mechanism, which control urinary output and fluid intake, respectively. - In so doing, they make needed fluid exchanges between the ECF and the external environment to regulate the body's total fluid volume. - Accordingly, they have an important long-term influence on arterial blood pressure. - Of these measures, control of urinary output by the kidneys is the most crucial for maintaining blood pressure

Compensations for Respiratory Acidosis

- Compensatory measures act to restore pH to normal. 1. The chemical buffers immediately take up additional H+. 2. The respiratory mechanism usually cannot respond with compensatory increased ventilation because impaired respiration is the problem in the first place. 3. Thus, the kidneys are most important in compensating for respiratory acidosis. They conserve all the filtered HCO3 - and add new HCO3- to the plasma while simultaneously secreting and, accordingly, excreting more H+. - As a result, HCO3 2 stores in the body become elevated. In our example, the plasma [HCO3 -] is doubled, so the [HCO3 -]/[CO2] ratio is 40/2 rather than 20/2 as it was in the uncompensated state. - A ratio of 40/2 is equivalent to a normal 20/1 ratio, so pH is once again the normal 7.4. - Enhanced renal conservation of HCO3 - has fully compensated for CO2 accumulation, thus restoring pH to normal, although both [CO2] and [HCO3 -] are now distorted. - Note that maintaining a normal pH depends on preserving a normal ratio between [HCO3 -] and [CO2], no matter what the absolute values of each of these buffer components are. (Bear in mind that the values used are only representative. Deviations in pH actually occur over a range, and the degree to which compensation can be accomplished varies.)

Compensations for Respiratory Alkalosis

- Compensatory measures act to shift pH back toward normal. ■ The chemical buffer systems liberate H+ to diminish the severity of the alkalosis. ■ As plasma [CO2] and [H+] fall below normal because of excessive ventilation, two of the normally potent stimuli for driving ventilation are removed. This effect tends to "put brakes" on the extent to which some nonrespiratory factors such as fever or anxiety can overdrive ventilation. Therefore, hyperventilation does not continue completely unabated. ■ If the situation continues for a few days, the kidneys compensate by conserving H+ and excreting more HCO3 -. If, as in our example, HCO3 - stores are reduced by half by loss of HCO3 - in the urine, the [HCO3 -]/ [CO2] ratio becomes 10/0.5, equivalent to the normal 20/1. Therefore, the pH is restored to normal by reducing the HCO3 - load to compensate for the CO2 loss.

Causes of Hypertonicity (Dehydration)

- Dehydration with accompanying hypertonicity can be brought about in three ways: 1. Insufficient H2O intake, such as might occur during desert travel or might accompany difficulty in swallowing 2. Excessive H2O loss, such as might occur during heavy sweating, vomiting, or diarrhea (even though both H2O and solutes are lost during these conditions, relatively more H2O is lost, so the remaining solutes become more concentrated) 3. Diabetes insipidus, a disease characterized by a deficiency of vasopressin

Control of Water Output in the Urine by Vasopressin

- Fluctuations in ECF osmolarity caused by imbalances between H2O input and H2O output are quickly compensated for by adjusting urinary excretion of H2O without changing the usual excretion of salt—that is, H2O reabsorption and excretion are partially dissociated from solute reabsorption and excretion, so the amount of free H2O retained or eliminated can be varied to quickly restore ECF osmolarity to normal. - Free H2O reabsorption and excretion are adjusted through changes in vasopressin secretion. - Throughout most of the nephron, H2O reabsorption is important in regulating ECF volume because salt reabsorption is accompanied by comparable H2O reabsorption. In the distal and collecting tubules, however, variable free H2O reabsorption can take place without comparable salt reabsorption because of the vertical osmotic gradient in the renal medulla to which this part of the tubule is exposed. - Vasopressin increases the permeability of this late part of the tubule to H2O. - Depending on the amount of vasopressin present, the amount of free H2O reabsorbed can be adjusted as necessary to restore ECF osmolarity to normal. - Vasopressin is produced by the hypothalamus, stored in the posterior pituitary gland, and released from the posterior pituitary on command from the hypothalamus.

hemoglobin buffer system

- Hemoglobin (Hb) buffers the H+ generated from metabolically produced CO2 in transit between the tissues and the lungs. - At the systemic capillary level, CO2 continuously diffuses into the blood from the tissue cells where it is being produced. - The greatest percentage of this CO2, along with H2O, forms H+ and HCO3 - under the influence of carbonic anhydrase within the red blood cells. - Most H+ generated from CO2 at the tissue level becomes bound to reduced Hb and no longer contributes to acidity of body fluids. - Were it not for Hb, blood would become too acidic after picking up CO2 at the tissues. - With the tremendous buffering capacity of the Hb system, venous blood is only slightly more acidic than arterial blood despite the large volume of H+ generating CO2 carried in venous blood. - At the lungs, the reactions are reversed and the resulting CO2 is exhaled.

Hypertonicity And Dehydration

- Hypertonicity of the ECF, the excessive concentration of ECF solutes, is usually associated with dehydration, or a negative free H2O balance

Input/Output of the Quantity of a Substance

- If the quantity of a substance is to remain stable within the body, its input through ingestion or metabolic production must be balanced by an equal output through excretion or metabolic consumption

The Barrier Between ECF And ICF: Cellular Plasma Membrane

- In contrast to the similar composition of plasma and interstitial fluid, the composition of the ECF differs considerably from that of the ICF. - Each cell is surrounded by a highly selective plasma membrane that permits passage of certain materials while excluding others. - Movement through the membrane barrier occurs by both passive and active means and may be highly discriminating. - Among the major differences between ECF and ICF are (1) the presence of cell proteins in the ICF that cannot permeate the enveloping membranes to leave the cells and (2) the unequal distribution of Na+ and K+ and their attendant anions (negatively charged ions) as a result of the action of the membrane-bound Na+-K+ pump present in all cells. - Because this pump actively transports Na+ out of and K+ into cells, Na+ is the primary ECF cation (positively charged ion) and K+ is the primary ICF cation ** Except for the extremely small, electrically unbalanced portion of the total intracellular and extracellular ions involved in membrane potential, most ECF and ICF ions are electrically balanced. In the ECF, Na+ is accompanied primarily by the anion chloride (Cl-) and to a lesser extent by bicarbonate (HCO3 -). The major intracellular anions are phosphate (PO4 3- ) and the negatively charged proteins trapped within the cell.

Causes of Respiratory Acidosis

- Possible causes include lung disease, depression of the respiratory center by drugs or disease, nerve or muscle disorders that reduce respiratory muscle ability, or (transiently) even the simple act of holding one's breath. - In uncompensated respiratory acidosis, [CO2] is elevated, whereas [HCO3 -] is normal, so the ratio is 20/2 (10/1) and pH is reduced.

Renal Handling of HCO3 - During Alkalosis

- In the opposite situation of alkalosis, the rate of H+ secretion diminishes, whereas the rate of HCO3 - filtration increases compared to normal. - When plasma [H+] is below normal, a smaller proportion of the HCO3 - pool than usual is tied up buffering H+, so plasma [HCO3 -] is elevated above normal. As a result, the rate of HCO3 - filtration correspondingly increases. Not all the filtered HCO3 - is reabsorbed because bicarbonate ions are in excess of secreted hydrogen ions in the tubular fluid and HCO3 - cannot be reabsorbed without first reacting with H+. - Excess HCO3 - is left in the tubular fluid to be excreted in the urine, thus reducing plasma [HCO3 -] while making the urine alkaline. - Furthermore, Type B intercalated cells come into play during alkalosis, further decreasing the excess HCO3 - load in the body by secreting HCO3 - into the urine.

Mechanism of Renal H+ Secretion in the Proximal Tubule

- In the proximal tubule, H+ is secreted by both primary active transport via H+ ATPase pumps and by secondary active transport via Na+-H+ antiporters. - The antiporters transport Na+ derived from glomerular filtrate in the opposite direction of H+ secretion, so H+ secretion and Na+ reabsorption are partially linked in the proximal tubule

Metabolic acidosis

- Metabolic acidosis (also known as nonrespiratory acidosis) encompasses all types of acidosis besides that caused by excess CO2 in body fluids. - In the uncompensated state, metabolic acidosis is always characterized by a reduction in plasma [HCO3 2], whereas [CO2] remains normal, producing an acidotic ratio of 10/1. - The problem may arise from excessive loss of HCO3 2-rich fluids from the body or from an accumulation of noncarbonic acids. - In the latter case, plasma HCO3 - is used up in buffering the additional H+.

Causes of Metabolic Acidosis

- Metabolic acidosis is the type of acid-base disorder most frequently encountered. - Here are its most common causes: 1. Severe diarrhea. During digestion, a HCO3 - rich digestive juice is normally secreted into the digestive tract by the pancreas and is later reabsorbed back into the plasma when digestion is completed. During diarrhea, this HCO3 - is lost from the body rather than reabsorbed. Because of the loss of HCO3 -, less HCO3 - is available to buffer H+, leading to more free H+ in the body fluids. 2. Diabetes mellitus. Abnormal fat metabolism resulting from the inability of cells to preferentially use glucose because of inadequate insulin action leads to formation of excess keto acids whose dissociation increases plasma [H+]. 3. Strenuous exercise. When muscles resort to anaerobic glycolysis during strenuous exercise, excess lactic acid (lactate) is produced, raising plasma [H+]. 4. Uremic acidosis. In severe renal failure (uremia), the kidneys cannot rid the body of even the normal amounts of H+ generated from noncarbonic acids formed by ongoing metabolic processes, so H+ starts to accumulate in the body fluids. ** Also, the kidneys cannot conserve an adequate amount of HCO3 - for buffering the normal acid load.

Filtered Phosphate as a Urinary Buffer

- Normally, secreted H+ is first buffered by the phosphate buffer system, which is in the tubular fluid because excess ingested phosphate has been filtered but not reabsorbed. - The basic member of the phosphate buffer pair binds with secreted H+. - When H+ secretion is high, the buffering capacity of urinary phosphates is exceeded. - The kidneys can only control the quantity of phosphate reabsorbed. - They can do nothing about the quantity of phosphate filtered and available for reabsorption; that depends on how much phosphate has been consumed. - As soon as all basic phosphate ions that are coincidentally excreted (because of dietary excess) have soaked up H+, the acidity of the tubular fluid quickly rises as more H+ ions are secreted. - Without additional buffering capacity from another source, H+ secretion would soon halt abruptly as the free [H+] in the tubular fluid quickly rose to the critical limiting level

Factors Regulated to Maintain Water Balance

- Of the many sources of H2O input and output, only two can be regulated to maintain H2O balance. - On the intake side, thirst influences the amount of fluid ingested; on the output side, the kidneys can adjust how much urine is formed. - Controlling H2O output in the urine is the most important mechanism in controlling H2O balance. - Some of the other factors are regulated, but not for maintaining H2O balance. Food intake is subject to regulation to maintain energy balance, and control of sweating is important in maintaining body temperature. Metabolic H2O production and insensible losses are unregulated

Ions Responsible for ECF and ICF Osmolarity

- Osmosis occurs across the cellular plasma membranes only when a difference in concentration of non-penetrating solutes exists between the ECF and the ICF. - Solutes that can penetrate a barrier separating two fluid compartments quickly become equally distributed between the two compartments and thus do not contribute to osmotic differences. - Na+ and accompanying Cl-, being by far the most abundant solutes in the ECF in terms of numbers of particles, account for most ECF osmotic activity. - In contrast, K+ and its accompanying intracellular anions are responsible for ICF osmotic activity. - Even though small amounts of Na+ and K+ passively diffuse across the plasma membrane all the time, these ions behave as if they were nonpenetrating because of Na+-K+ pump activity. - Any Na+ that passively diffuses down its electrochemical gradient into the cell is promptly pumped back outside, so the result is the same as if Na+ were barred from the cells. - In reverse, K+ in effect remains trapped within the cells. - Normally, the osmolarities of the ECF and ICF are the same because the total concentration of K+ and other effectively nonpenetrating solutes inside the cells is equal to the total concentration of Na+ and other effectively nonpenetrating solutes in the fluid surrounding the cells. - Even though nonpenetrating solutes in the ECF and ICF differ, their concentrations are normally identical, and the number (not the nature) of the unequally distributed particles per volume determines the fluid's osmolarity. - Because the osmolarities of the ECF and ICF are normally equal, no net movement of H2O usually occurs into or out of the cells. - Therefore, cell volume normally remains constant

Which fluid can be acted on directly to control its volume and composition?

- Plasma is the only fluid that can be acted on directly to control its volume and composition. - This fluid circulates through all the reconditioning organs that perform homeostatic adjustments. - However, because of the free exchange across the capillary walls, if the volume and composition of the plasma are regulated, the volume and composition of the interstitial fluid bathing the cells are likewise regulated. - Thus, any control mechanism that operates on plasma in effect regulates the entire ECF. - The ICF in turn is influenced by changes in the ECF to the extent permitted by the permeability of membrane barriers surrounding the cells

Causes of Respiratory Alkalosis

- Possible causes of respiratory alkalosis include fever, anxiety, and aspirin poisoning, all of which excessively stimulate ventilation without regard to the status of O2, CO2, or H1 in the body fluids. - Respiratory alkalosis also occurs as a result of physiological mechanisms at high altitude. - When the low concentration of O2 in arterial blood reflexly stimulates ventilation to obtain more O2, too much CO2 is blown off, inadvertently leading to an alkalotic state. - If we look at the biochemical abnormalities in uncompensated respiratory alkalosis, the increase in pH reflects a reduction in [CO2] (half the normal value in our example), whereas [HCO3 -] remains normal. - This yields an alkalotic ratio of 20/0.5, which is comparable to 40/1.

Mechanism of Renal H+ Secretion in the Distal and Collecting Tubules

- Recall that two types of cells are located in the distal and collecting tubules, principal cells and intercalated cells. - Principal cells are the ones with which you are already familiar. - These are the cells that play an important role in Na+ (and subsequently Cl- —that is, salt) balance and in K+ balance under the influence of aldosterone. - They are also the cells involved in maintaining H2O balance under the influence of vasopressin. - Intercalated cells, which are interspersed among the principal cells, are involved in fine regulation of acid-base balance. T - here are two types of intercalated cells, Type A (most abundant) and Type B

Regulatory Factors that Do Not Link Vasopressin and Thirst

- Several factors affect vasopressin secretion but not thirst. - As described earlier, vasopressin is stimulated by stress related inputs such as pain and trauma that have nothing directly to do with maintaining H2O balance. - In fact, H2O retention from the inappropriate secretion of vasopressin can bring about a hypotonic H2O imbalance. - In contrast, alcohol and caffeine inhibit vasopressin secretion and can lead to ECF hypertonicity by promoting excessive free H2O excretion. - One stimulus that promotes thirst but not vasopressin secretion is a direct effect of dryness of the mouth. - Nerve endings in the mouth are directly stimulated by dryness, which causes an intense sensation of thirst that can often be relieved merely by moistening the mouth even though no H2O is actually ingested. - A dry mouth can exist when salivation is suppressed by factors unrelated to the body's H2O content, such as nervousness, excessive smoking, or certain drugs. - Factors that affect vasopressin secretion or thirst but have nothing directly to do with the body's need for H2O are usually short-lived. - The dominant, long-standing control of vasopressin and thirst is directly correlated with the body's state of H2O—namely, by the status of ECF osmolarity and, to a lesser extent, by ECF volume.

Oral Metering

- Some kind of "oral H2O metering" appears to exist, at least in animals. - A thirsty animal will rapidly drink only enough H2O to satisfy its H2O deficit. - It stops drinking before the ingested H2O has had time to be absorbed from the digestive tract and return the ECF compartment to normal. - Receptors in the mouth, pharynx (throat), and upper digestive tract signal that enough H2O has been consumed. - This mechanism seems to be less effective in humans because we frequently drink more than is necessary to meet the needs of our bodies or, conversely, may not drink enough to make up a deficit.

What is the most important buffer system?

- The H2CO3:HCO3 - buffer pair is the most important buffer system in the ECF for buffering pH changes brought about by causes other than fluctuations in CO2-generated H2CO3 - It is an effective ECF buffer system for two reasons. - First, H2CO3 and HCO3 - are abundant in the ECF, so this system is readily available to resist changes in pH. - Second, and more importantly, each component of this buffer pair is closely regulated. The kidneys regulate HCO3 -, and the respiratory system regulates CO2, which generates H2CO3. - Thus, in the body the H2CO3:HCO3 - buffer system includes involvement of CO2 - When new H+ is added to the plasma from any source other than CO2 (for example, through lactic acid released into the ECF from exercising muscles), the preceding reaction is driven toward the left side of the equation. - As the extra H+ binds with HCO3 -, it no longer contributes to the acidity of body fluids, so the rise in [H1] abates. - In the converse situation, when the plasma [H+] occasionally falls below normal for some reason other than a change in CO2 (such as the loss during vomiting of plasma-derived HCl in the digestive juices in the stomach), the reaction is driven toward the right side of the equation. - Dissolved CO2 and H2O in the plasma form H2CO3, which generates additional H+ to make up for the H+ deficit. - In so doing, the H2CO3:HCO3 - buffer system resists the fall in [H+].

Henderson-Hasselbalch Equation

- The Henderson-Hasselbalch equation states the relationship between hydrogen ions and the members of a buffer pair. - pH = pK + log of bicarbonate ion concentration carbonic acid concentration - With a pK of 6.1, the log of the ratio of the two concentrations stated leads to the computation of the pH. - For example, if the ratio is 20/1, its log is 1.3. 6.1 plus 1.3 = 7.4; This is the normal pH of the blood. - pH also equals bicarbonate ions controlled by the kidneys and carbon dioxide controlled by the lungs

Proportion of H2O in the Major Fluid Compartment

- The ICF compartment composes about two thirds of the total body H2O. - Even though each cell contains a unique mixture of constituents, these trillions of minute fluid compartments are similar enough to be considered collectively as one large fluid compartment. - The remaining third of the body H2O found in the ECF compartment is further subdivided into plasma and interstitial fluid. - Plasma, the fluid portion of blood, makes up about a fifth of the ECF volume. - Interstitial fluid, the fluid that lies in the spaces between cells and makes exchanges with the cells, represents the other four fifths of the ECF compartment

When plasma [H+] falls below normal during alkalosis, renal responses include the following:

1. Decreased secretion and subsequent reduced excretion of H+ in the urine, conserving H+ and increasing plasma [H+] 2. Incomplete reabsorption of filtered HCO3 - coupled with secretion of HCO3 -, leading to increased excretion of HCO3 - and reduced plasma [HCO3 -] ** Note that to compensate for acidosis, the kidneys acidify urine (by getting rid of extra H+) and alkalinize plasma (by conserving HCO3 -) to bring plasma pH to normal. In the opposite case—alkalosis—the kidneys make urine alkaline (by eliminating excess HCO3 -) while acidifying plasma (by conserving H+).

the glomerular filtration rate (GFR)

- The amount of Na+ filtered is controlled by regulating the GFR. - The amount of Na+ filtered is equal to the plasma Na+ concentration times the GFR. - At any given plasma Na+ concentration, any change in the GFR correspondingly changes the amount of Na+ and accompanying fluid that are filtered. - Thus, control of the GFR can adjust the amount of Na+ filtered each minute. - Recall that the GFR is deliberately changed to alter the amount of salt and fluid filtered, as part of the general baroreceptor reflex response to a change in blood pressure. - Changes in Na+ load in the body are not sensed as such; instead, they are monitored indirectly through the effect that the Na+ load ultimately has on blood pressure. - It is fitting that baroreceptors that monitor fluctuations in blood pressure bring about adjustments in the amounts of Na+ filtered and eventually excreted absorbed also depends on regulatory systems that play an important role in controlling blood pressure. - Although Na+ is reabsorbed throughout most of the tubule's length, only its reabsorption in the late parts of the tubule is subject to control. - The main factor controlling the extent of Na+ reabsorption in the distal and collecting tubules is the powerful renin- angiotensin-aldosterone system (RAAS), which promotes Na+ reabsorption and thereby Na+ retention. - Sodium retention, in turn, promotes osmotic retention of H2O and subsequent expansion of plasma volume and elevation of arterial blood pressure. - Appropriately, this Na+-conserving system is activated by a reduction in NaCl, ECF volume, and arterial blood pressure ** Thus, control of GFR and Na+ reabsorption are interrelated, and both are intimately tied in with long-term regulation of ECF volume as reflected by blood pressure

Three Lines of Defense Against Changes in [H+]

- The key to H+ balance is maintaining normal alkalinity of the ECF despite this constant onslaught of acid. - The generated free H+ must be largely removed from solution while in the body and ultimately must be eliminated so that the pH of body fluids can remain within the narrow range compatible with life. - Mechanisms must also exist to compensate rapidly for the occasional situation in which the ECF becomes too alkaline. - Three lines of defense against changes in [H+] operate to maintain [H+] of body fluids at a nearly constant level despite unregulated input: (1) the chemical buffer systems (2) the respiratory mechanism of pH control (3) the renal mechanism of pH control

Renal Handling of H+ During Acidosis and Alkalosis

- The kidneys are able to exert a fine degree of control over body pH. - Renal handling of H+ and HCO3 - depends primarily on a direct effect of the plasma's acid-base status on the kidney's tubular cells. - Under normal circumstances, the proximal tubular cells and Type A intercalated cells are predominantly active, promoting net H+ secretion and HCO3 - reabsorption. - This pattern of activity is adjusted when pH deviates from the set point

The protein buffer system

- The most plentiful buffers of the body fluids are the proteins, including the intracellular proteins and the plasma proteins. - Proteins are excellent buffers because they contain both acidic and basic groups that can give up or take up H+. - Quantitatively, the protein system is most important in buffering changes in [H+] in the ICF because of the sheer abundance of the intracellular proteins. - The more limited number of plasma proteins reinforces the H2CO3:HCO3 - system in extracellular buffering.

Poor Control of Salt Intake

- The only avenue for salt input is ingestion, which typically is well in excess of the body's need for replacing obligatory salt losses. - In our example of a typical daily salt balance, salt intake is 10 g per day; yet 0.5 g of salt per day is adequate to replace the small amounts of salt usually lost in sweat and feces. (The average American salt intake is about 8.5 to 10 g per day, although many people are consciously reducing their salt intake.) - Because humans typically consume salt in excess of our needs, obviously our salt intake is not well controlled. - Carnivores (meat eaters) and omnivores (eaters of meat and plants, like humans), which naturally get enough salt in fresh meat (meat contains an abundance of salt-rich ECF), normally do not display a physiological appetite to seek additional salt. - In contrast, herbivores (plant eaters), which lack salt naturally in their diets, develop salt hunger and will travel miles to a salt lick. - Humans have a hedonistic (pleasure-seeking) rather than a regulatory appetite for salt; we consume salt because we like it rather than because we have a physiological need.

Acidosis and Alkalosis in the Body

- The pH of arterial blood is normally 7.45 and the pH of venous blood is 7.35, for an average blood pH of 7.4. - The pH of venous blood is slightly lower (more acidic) than that of arterial blood because H+ is generated by the formation of H2CO3 from CO2 picked up at the tissue capillaries. - Acidosis exists whenever blood pH falls below 7.35, whereas alkalosis occurs when blood pH is above 7.45. - Note that the reference point for determining the body's acid-base status is not the chemically neutral pH of 7.0 but the normal blood pH of 7.4. - Thus, a blood pH of 7.2 is considered acidotic even though in chemistry a pH of 7.2 is considered basic. - An arterial pH of less than 6.8 or greater than 8.0 is not compatible with life. - Because death occurs if arterial pH falls outside the range of 6.8 to 8.0 for more than a few seconds, [H+] in the body fluids must be carefully regulated.

Acidic and Basic Solutions in Chemistry

- The pH of pure H2O is 7.0, which is considered chemically neutral. - An extremely small proportion of H2O molecules dissociate into H+ and hydroxyl (OH-) ions. - Because an equal number of acidic H+ and basic OH are formed, H2O is neutral, being neither acidic nor basic. - Solutions having a pH less than 7.0 contain a higher [H+] than pure H2O and are considered acidic. Solutions having a pH value greater than 7.0 have a lower [H+] than pure H2O and are considered basic, or alkaline

In short, when plasma [H+] increases above normal during acidosis, renal compensation includes the following:

1. Increased secretion and subsequent increased excretion of H+ in the urine, thereby eliminating the excess H+ and decreasing plasma [H+] 2. Reabsorption of all filtered HCO3 -, plus addition of new HCO3 - to the plasma, resulting in increased plasma [HCO3 -]

Phosphate Buffer System

- The phosphate buffer system consists of an acid phosphate salt (NaH2PO4) that can donate a free H+ when the [H+] falls and a basic phosphate salt (Na2HPO4) that can accept a free H+ when the [H+] rises. - Basically, this buffer pair can alternately switch a H+ for a Na+ as demanded by the [H+]. - Even though the phosphate pair is a good buffer, its concentration in the ECF is rather low, so it is not very important as an ECF buffer. - Because phosphates are most abundant within the cells, this system contributes significantly to intracellular buffering, being rivaled only by the more plentiful intracellular proteins. - Even more important, the phosphate system serves as an excellent urinary buffer. - Humans normally consume more phosphate than needed. - The excess phosphate filtered through the kidneys is not reabsorbed but remains in the tubular fluid to be excreted (because the renal threshold for phosphate is exceeded. - This excreted phosphate buffers urine as it forms by removing from solution the H+ secreted into the tubular fluid. - None of the other body-fluid buffer systems are present in the tubular fluid to play a role in buffering urine during its formation. - Most or all of the filtered HCO3 - and CO2 (alias H2CO3) are reabsorbed, whereas Hb and plasma proteins are not even filtered.

Role of Hypothalamic Osmoreceptors

- The predominant excitatory input for both vasopressin secretion and thirst comes from hypothalamic osmoreceptors located near the vasopressin-secreting cells and thirst center. - These osmo-receptors monitor the osmolarity of fluid surrounding them, which in turn reflects the concentration of the entire internal fluid environment. - As ECF osmolarity increases (too little H2O) and the need for H2O conservation increases, vasopressin secretion and thirst are both stimulated. - As a result, reabsorption of H2O in the distal and collecting tubules is increased so that urinary output is reduced and H2O is conserved, while H2O intake is simultaneously encouraged. - These actions restore depleted H2O stores, thus relieving the hypertonic condition by diluting the solutes to normal concentration. - In contrast, H2O excess, manifested by reduced ECF osmolarity, prompts increased urinary output (through decreased vasopressin release) and suppresses thirst, which together reduce the water load in the body.

Internal Pool

- The quantity of any particular substance in the ECF is a readily available internal pool. - The amount of the substance in the pool may be increased either by transferring more in from the external environment (usually by ingestion) or by metabolically producing it within the body. - Substances may be removed from the body by being excreted to the outside or by being used up in a metabolic reaction

The respiratory system role in acid-base

- The respiratory system plays an important role in acid-base balance through its ability to alter pulmonary ventilation and consequently to alter excretion of H+-generating CO2. - The level of respiratory activity is governed in part by arterial [H+], as follows: ■ An increase in arterial [H+] as the result of a nonrespiratory (or metabolic) cause brings about reflex stimulation of the respiratory center in the brain stem via the peripheral chemoreceptors to increase pulmonary ventilation (the rate at which gas is exchanged between the lungs and the atmosphere). As the rate and depth of breathing increase, more CO2 than usual is blown off. Because hydration of CO2 generates H1, removal of CO2 in essence removes acid from this source from the body, offsetting extra H+ present from a nonrespiratory source. ■ Conversely, when arterial [H+] falls because of a nonrespiratory cause, pulmonary ventilation is reflexly reduced. As a result of slower, shallower breathing, metabolically produced CO2 diffuses from the cells into the blood faster than it is removed from the blood by the lungs, so higher-than-usual amounts of acid-forming CO2 accumulate in the blood, thus restoring [H+] toward normal. ** The lungs are extremely important in maintaining [H+]. Every day they remove from body fluids what amounts to 100 times more H+ derived from CO2 than the kidneys remove from sources other than CO2-H+. Furthermore, the respiratory system, through its ability to regulate arterial [CO2], can adjust the amount of H+ added to body fluids from this source as needed to restore pH toward normal when fluctuations occur in [H1] from sources other than CO2-H+.

Steps of Coupling of HCO3 - Reabsorption with H1 Secretion

- The same steps are involved in HCO3 - reabsorption in the proximal tubular cells, except in addition to having basolateral Cl- -HCO3 - antiporters, these cells also have more abundant basolateral Na- -HCO3 - symporters that simultaneously reabsorb Na+ and HCO3 -. - Normally, slightly more H+ is secreted into the tubular fluid than HCO3 - is filtered. Accordingly, all the filtered HCO3 - is usually reabsorbed because secreted H+ is available in the tubular fluid to combine with it to form highly reabsorbable CO2 and H2O. - By far the largest part of the secreted H+ combines with HCO3 - and is not excreted because it is "used up" in HCO3 - reabsorption. - However, the slight excess of secreted H+ that is not matched by filtered HCO3 - is excreted in the urine. This normal H+ excretion rate keeps pace with the normal rate of noncarbonic acid H+ production.

Acid-Base Balance

- The term acid-base balance refers to the precise regulation of free (that is, unbound) hydrogen ion (H+) concentration in the body fluids. - To indicate the concentration of a chemical, its symbol is enclosed in square brackets. Thus, [H+] designates H+ concentration.

The Barrier Between Plasma and Interstitial Fluid: Blood Vessel Walls

- The two components of the ECF—plasma and interstitial fluid—are separated by the walls of the blood vessels. - However, H2O and all plasma constituents except for plasma proteins are continuously and freely exchanged between plasma and interstitial fluid by passive means across the thin, pore-lined capillary walls. - Accordingly, plasma and interstitial fluid are nearly identical in composition, except that interstitial fluid lacks plasma proteins. - Any change in one of these ECF compartments is quickly reflected in the other compartment because they are constantly mixing.

Control of Water Input by Thirst

- Thirst is the subjective sensation that drives you to ingest H2O. - The thirst center is located in the hypothalamus close to the vasopressin-secreting cells.

Causes of Metabolic Alkalosis

- This condition arises most commonly from the following: 1. Vomiting causes abnormal loss of H+ from the body as a result of lost acidic gastric (stomach) juices. HCl is secreted into the stomach lumen during digestion. In the course of gastric HCl secretion, HCO3 - is added to the plasma. This HCO3 - is neutralized by H+ as the gastric secretions are eventually reabsorbed back into the plasma, so normally there is no net addition of HCO3 - to the plasma from this source. However, when the secreted acid is lost from the body during vomiting instead of being reabsorbed, not only is plasma [H+] decreased, but also reabsorbed H1 is no longer available to neutralize the extra HCO3 - added to the plasma during gastric HCl secretion. Thus, loss of HCl in effect increases plasma [HCO3 -]. (In contrast, with "deeper" vomiting, HCO3 - in the digestive juices secreted into the upper intestine may be lost in the vomit, resulting in acidosis instead of alkalosis.) 2. Ingestion of alkaline drugs can produce alkalosis, such as when baking soda (NaHCO3, which dissociates in solution into Na+ and HCO3 -) is used as a self-administered remedy for treating gastric hyperacidity. By neutralizing excess acid in the stomach, HCO3 - relieves the symptoms of stomach irritation and heartburn; but when more HCO3 - than needed is ingested, the extra HCO3 - is absorbed from the digestive tract and increases plasma [HCO3 -]. The extra HCO3 - binds with some of the free H1 normally present in plasma from noncarbonic acid sources, reducing free [H+]. (In contrast, commercial alkaline products for treating gastric hyperacidity are not absorbed from the digestive tract to any extent and therefore do not alter the body's acid-base status.)

H2CO3:HCO3- buffer system on pH

- This system cannot buffer changes in pH induced by fluctuations in H2CO3. - A buffer system cannot buffer itself. - Consider, for example, the situation in which the plasma [H+] is elevated by CO2 retention from a respiratory problem. - The rise in CO2 drives the reaction to the right according to the law of mass action, elevating [H+]. - The increase in [H+] occurs as a result of the reaction being driven to the right by an increase in CO2, so the elevated [H+] cannot drive the reaction to the left to buffer the increase in [H+]. - Only if the increase in [H+] is brought about by some mechanism other than CO2 accumulation can this buffer system be shifted to the CO2 side of the equation and effectively reduce [H+]. - Likewise, in the opposite situation, the H2CO3:HCO3 - buffer system cannot compensate for a reduction in [H+] from a deficit of CO2 by generating more H+-yielding H2CO3 when the problem in the first place is a shortage of H2CO3 -forming CO2. - Other mechanisms are available for resisting fluctuations in pH caused by changes in CO2 levels.

Precise Control of Salt Output in the Urine

- To maintain salt balance, excess ingested salt must be excreted in the urine. - The three avenues for salt output are obligatory loss of salt in sweat and feces and controlled excretion of salt in urine. - The total amount of sweat produced is unrelated to salt balance, being determined instead by factors that control body temperature. - The small salt loss in feces is not subject to control. - Except when sweating heavily or during diarrhea, the body uncontrollably loses only about 0.5 g of salt per day. - This amount is the only salt that normally needs to be replaced by salt intake. - Because salt consumption is typically far more than the meager amount needed to compensate for uncontrolled losses, the kidneys precisely excrete the excess salt in the urine to maintain salt balance. - In our example, 9.5 g of salt are eliminated in the urine per day so that total salt output exactly equals salt input. - By regulating the rate of urinary salt excretion (that is, by regulating the rate of Na+ excretion, with Cl- following along), the kidneys normally keep the total Na1 load (tacitly including the total Cl- load) in the ECF constant despite any notable changes in dietary intake of salt or unusual losses through sweating or diarrhea. - As a reflection of keeping the total Na+ load in the ECF constant, the ECF volume, in turn, is maintained within the narrowly prescribed limits essential for normal circulatory function

Type A intercalated cells

- Type A intercalated cells are H+-secreting, HCO3 - reabsorbing, K+-reabsorbing cells. - They actively secrete H+ into the tubular lumen via two types of primary active transport mechanisms: H+ ATPase pumps and H+-K+ ATPase pumps. - The latter secrete H+ in exchange for uptake (reabsorption) of K+. - Both of these types of carriers are located at the luminal membrane in Type A cells. - The HCO3 + generated in the process of forming H+ from CO2 under the influence of carbonic anhydrase enters the blood (is reabsorbed) in exchange for Cl2 at the basolateral membrane via Cl- -HCO3 - antiporters.

Type B intercalated cells

- Type B intercalated cells are HCO3 - -secreting, H+-reabsorbing, K+-secreting cells, just the opposite actions of the Type A intercalated cells. - In contrast to Type A cells, the active H+ ATPase pumps and H+-K+ ATPase pumps are located at the basolateral membrane and the Cl- -HCO3 - antiporters are located at the luminal membrane. In this case, when H+ and HCO3 - are generated from the hydration of CO2 under the influence of carbonic anhydrase, HCO3 2 moves into the tubular lumen (is secreted) in exchange for Cl-, and H+ is reabsorbed into the plasma in exchange for K+ across the basolateral membrane. - Even though the Type B intercalated cells actively secrete K+, the principal cells under the control of aldosterone actively secrete quantitatively much more K+. ** Type A intercalated cells are more active than Type B intercalated cells under normal circumstances, and their activity increases even more during acidosis. - Type B intercalated cells become more active during alkalosis.

Only a narrow pH range is compatible with life because even small changes in [H+] have dramatic effects on normal cell function, as the following consequences indicate:

1. Changes in excitability of nerve and muscle cells are among the major clinical manifestations of pH abnormalities. - The major clinical effect of increased [H+] (acidosis) is depression of the central nervous system (CNS). Acidotic patients become disoriented and, in more severe cases, eventually die in a state of coma. - In contrast, the major clinical effect of decreased [H+] (alkalosis) is overexcitability of the nervous system, first the peripheral nervous system and later the CNS. Peripheral nerves become so excitable that they fire even in the absence of normal stimuli. Such overexcitability of the afferent (sensory) nerves gives rise to abnormal "pins-andneedles" tingling sensations. Overexcitability of efferent (motor) nerves brings about muscle twitches and, in more pronounced cases, severe muscle spasms. Death may occur in extreme alkalosis because spasm of the respiratory muscles seriously impairs breathing. Alternatively, patients with severe alkalosis may die of convulsions resulting from overexcitability of the CNS. In less serious situations, CNS overexcitability is manifested as extreme nervousness. 2. Hydrogen ion concentration exerts a marked influence on enzyme activity. Even slight deviations in [H+] alter the shape and activity of protein molecules. Because enzymes are proteins, a shift in the body's acid-base balance disturbs the normal pattern of metabolic activity catalyzed by these enzymes. 3. Changes in [H+] influence K1 levels in the body. When reabsorbing Na+ from the filtrate, the renal tubular cells secrete either K+ or H+ in exchange. Normally, they secrete a preponderance of K+ compared to H+. Because of the intimate relationship between secretion of H+ and that of K+ by the kidneys, when H+ secretion increases to compensate for acidosis, less K+ than usual can be secreted; conversely, when H+ secretion is reduced during alkalosis, more K+ is secreted than normal. The resulting changes in ECF [K+] can lead to cardiac abnormalities, among other detrimental consequences.

Secreted NH3 as a Urinary Buffer

- When acidosis exists, the tubular cells secrete ammonia (NH3) into the tubular fluid once the normal urinary phosphate buffers are saturated. - This NH3 enables the kidneys to continue secreting additional H+ ions because NH3 combines with free H+ in the tubular fluid to form ammonium ion (NH4 +) - The tubular membranes are not very permeable to NH4 +, so the ammonium ions remain in the tubular fluid and are lost in the urine, each one taking a H+ with it. - Thus, NH3 secreted during acidosis buffers excess H+ in the tubular fluid so that large amounts of H+ can be secreted into the urine before the pH falls to the limiting value of 4.5. - Were it not for NH3 secretion, the extent of H+ secretion would be limited to whatever phosphate-buffering capacity coincidentally happened to be present as a result of more phosphate being consumed than was needed. - In contrast to the phosphate buffers, which are in the tubular fluid because they have been filtered but not reabsorbed, NH3 is deliberately synthesized from the amino acid glutamine within the tubular cells. - Once synthesized, NH3 readily diffuses passively down its concentration gradient into the tubular fluid—that is, it is secreted into the urine. - The rate of NH3 secretion is controlled by a direct effect on the tubular cells of the amount of excess H+ to be transported in the urine. - When someone has been acidotic for more than two or three days, the rate of NH3 production increases substantially. - This extra NH3 provides additional buffering capacity to allow H+ secretion to continue after the normal phosphate-buffering capacity is overwhelmed during renal compensation for acidosis.

Renal Handling of HCO3 - During Acidosis

- When plasma [H+] is elevated during acidosis, more H+ is secreted than normal. At the same time, less HCO3 - is filtered than normal because more of the plasma HCO3 - is used up in buffering the excess H+ in the ECF. - This greater-than-usual inequity between filtered HCO3 - and secreted H+ has two consequences. - First, more of the secreted H1 is excreted in the urine because more hydrogen ions are entering the tubular fluid at a time when fewer are needed to reabsorb the reduced quantities of filtered HCO3 -. - In this way, extra H+ is eliminated from the body, making the urine more acidic than normal. - Second, because excretion of H+ is linked with the addition of new HCO3 - to the plasma, more HCO3 - than usual enters the plasma passing through the kidneys. - This additional HCO3 - is available to buffer excess H1 present in the body

Role of Angiotensin II

- Yet another stimulus for increasing both thirst and vasopressin is angiotensin II. - When RAAS is activated to conserve Na+, angiotensin II, in addition to stimulating aldosterone secretion, acts directly on the brain to give rise to the urge to drink and concurrently stimulates vasopressin to enhance renal H2O reabsorption. - The resultant increased H2O intake and decreased urinary output help correct the reduction in ECF volume that triggered RAAS

Regulation of fluid balance involves two separate components:

- control of extracellular fluid (ECF) volume, of which circulating plasma volume is a part, and control of ECF osmolarity (solute concentration). - The kidneys control ECF volume by maintaining salt balance and control ECF osmolarity by maintaining water balance. - The kidneys maintain this balance by adjusting the output of salt and water in the urine as needed to compensate for variable input and abnormal losses of these constituents.

Body H2O is distributed between two major fluid compartments:

- fluid within the cells, or intracellular fluid (ICF), and fluid surrounding the cells, or extracellular fluid (ECF)

Sources of H+ in the Body

1. ) Carbonic acid formation. The major source of H+ is from metabolically produced CO2. - Cellular oxidation of nutrients yields energy, with CO2 and H2O as end products. - Without catalyst influence, CO2 and H2O slowly form H2CO3, which then rapidly partially dissociates to liberate free H+ and HCO3 - 2.) Inorganic acids produced during breakdown of nutrients. Dietary proteins found abundantly in meat contain a large quantity of sulfur and phosphorus. When these nutrient molecules are broken down, sulfuric acid and phosphoric acid are produced as by-products. Being moderately strong acids, these two inorganic acids largely dissociate, liberating free H+ into the body fluids. Acids are likewise generated during breakdown of the proteins in grains and dairy products. In contrast, breakdown of fruits and vegetables produces bases that, to some extent, neutralize acids derived from meat, grain, and dairy protein metabolism. Generally, however, more acids than bases are produced during breakdown of ingested food, leading to an excess of these acids. 3.) Organic acids resulting from intermediary metabolism. Numerous organic acids are produced during normal intermediary metabolism. For example, fatty acids are produced during fat metabolism, and muscles produce lactic acid (lactate) during heavy exercise. These acids partially dissociate to yield free H+.

The following rules of thumb apply when examining acid-base imbalances before any compensations take place:

1. A change in pH that has a respiratory cause is associated with an abnormal [CO2], giving rise to a change in H2CO3 - generated H+. - In contrast, a pH deviation of metabolic origin is associated with an abnormal [HCO3 -] resulting from an inequality between the amount of HCO3 - available and the amount of H+ generated from noncarbonic acids that the HCO3 - must buffer. 2. Anytime the [HCO3 2]/[CO2] ratio falls below 20/1, an acidosis exists. - The log of any number lower than 20 is less than 1.3 and, when added to the pK of 6.1, yields an acidotic pH below 7.4. - Anytime the ratio exceeds 20/1, an alkalosis exists. - The log of any number greater than 20 is more than 1.3 and, when added to the pK of 6.1, yields an alkalotic pH above 7.4

Short-Term Control Measures to Maintain Blood Pressure

1. The baroreceptor reflex alters both cardiac output and total peripheral resistance to adjust blood pressure in the proper direction through autonomic nervous system effects on the heart and blood vessels. Cardiac output and total peripheral resistance are both increased to raise blood pressure when it falls too low, and conversely, both are decreased to reduce blood pressure when it rises too high. 2. Fluid shifts occur temporarily and automatically between plasma and interstitial fluid as a result of changes in the balance of hydrostatic and osmotic forces acting across the capillary walls that arise when plasma volume deviates from normal (see p. 357). A reduction in plasma volume is partially compensated for by a shift of fluid out of the interstitial compartment into the blood vessels, expanding the circulating plasma volume at the expense of the interstitial compartment. Conversely, when plasma volume is too large, much of the excess fluid shifts into the interstitial compartment. ** These two measures provide temporary relief to help keep blood pressure fairly constant, but they are not long-term solutions. Furthermore, these short-term compensatory measures have a limited ability to minimize a change in blood pressure. For example, if plasma volume is too inadequate, blood pressure remains too low no matter how vigorous the pump action of the heart, how constricted the resistance vessels, or what proportion of interstitial fluid shifts into the blood vessels.

Base

A base is a substance that can combine with a free H+ and thus remove it from solution. - A strong base can bind H+ more readily than a weak base can.

Control of free H2O balance is crucial for regulating:

ECF osmolarity. - Because increases in free H2O cause the ECF to become too dilute and deficits of free H2O cause the ECF to become too concentrated, the osmolarity of the ECF must be immediately corrected by restoring stable free H2O balance to avoid harmful osmotic fluid shifts into or out of the cells. - To maintain a stable H2O balance, H2O input must equal H2O output

Two factors are regulated to maintain fluid balance in the body:

ECF volume and ECF osmolarity - Although regulation of these two factors is interrelated, both depending on the relative NaCl and H2O loads in the body, the reasons why and the mechanisms by which they are controlled are notably different: 1. ECF volume must be closely regulated to help maintain blood pressure. Maintaining salt balance is of primary importance in the long-term regulation of ECF volume. 2. ECF osmolarity must be closely regulated to prevent swelling or shrinking of cells. Maintaining water balance is of primary importance in regulating ECF osmolarity.

All exchanges of H2O and other constituents between the ICF and the external world must occur through the:

ECF, so the ECF serves as an intermediary between the cells and the external environment. - Water added to the body fluids always enters the ECF first, and fluid always leaves the body via the ECF.

Compensations for Metabolic Acidosis

Except in uremic acidosis, metabolic acidosis is compensated for by both respiratory and renal mechanisms as well as by chemical buffers. ■ The buffers take up extra H+. ■ The lungs blow off additional H+ -generating CO2. ■ The kidneys excrete more H+ and conserve more HCO3 - ** When kidney disease causes metabolic acidosis, complete compensation is not possible because the renal mechanism is not available for pH regulation. - Recall that the respiratory system can compensate only up to 75% of the way toward normal. - Uremic acidosis is very serious because the kidneys cannot help restore pH all the way to normal.

negative balance

In contrast, when losses for a substance exceed its gains, a negative balance exists and the total amount of the substance in the body decreases

Controlling ECF osmolarity prevents changes in what?

ICF volume. - Maintaining fluid balance depends on regulating both ECF volume and ECF osmolarity. - Regulating ECF osmolarity is important in preventing changes in cell volume. - The osmolarity of a fluid is a measure of the concentration of the individual solute particles dissolved in it. - The higher the osmolarity, the higher the concentration of solutes or, to look at it differently, the lower the concentration of H2O. - Recall that water tends to move by osmosis down its own concentration gradient from an area of lower solute (higher H2O) concentration to an area of higher solute (lower H2O) concentration

How is carbonic acid formed?

Step 1. - Carbonic anhydrase catalyzes the formation of HCO3 - from metabolically produced CO Step 2. - Water dissociates, forming more OH- that can be used in Step 1, yielding H+ in the process ** - The OH- used up in step 1 is generated by step 2; as a result, there's no net loss or gain of OH-. - These reactions are reversible because they can proceed in either direction, depending on the concentrations of the substances involved as dictated by the law of mass action. - Within the systemic capillaries, the CO2 level in the blood increases as metabolically produced CO2 enters from the tissues. - This drives the reaction (with or without carbonic anhydrase) to the H+ side. - In the lungs, the reaction is reversed: CO2 diffuses from the blood flowing through the pulmonary capillaries into the alveoli (air sacs), from which it is expired to the atmosphere. - The resultant reduction in blood CO2 drives the reaction toward the CO2 side. H+ and HCO3 - form CO2 and H2O again. - The CO2 is exhaled while the hydrogen ions generated at the tissue level are incorporated into H2O molecules. - When the respiratory system can keep pace with the rate of metabolism, there is no net gain or loss of H+ in the body fluids from metabolically produced CO2. - When the rate of CO2 removal by the lungs does not match the rate of CO2 production at the tissue level, however, the resulting accumulation or deficit of CO2 leads to an excess or shortage, respectively, of free H1 in the body fluids.

H+ and pH designnation

The [H1] in the ECF is normally 4 x 10^-8 or 0.00000004 equivalents per liter, about 3 million times less than the [Na+] in the ECF. - The concept of pH was developed to express the low value of [H+] more conveniently. - Specifically, pH equals the logarithm (log) to the base 10 of the reciprocal of [H+].

Balance Concept

The balance between input of a substance through ingestion or metabolic production and its output through excretion or metabolic consumption - This relationship, known as the balance concept, is extremely important in maintaining homeostasis. - Not all input and output pathways apply to every body-fluid constituent. - For example, salt is not synthesized or used up by the body, so maintaining a stable salt concentration in the body fluids depends entirely on a balance between salt ingestion and salt excretion.

How are Vasopressin secretion and Thirst triggered (regulated)?

The hypothalamic control centers that regulate vasopressin secretion (and thus urinary output) and thirst (and thus drinking) act in concert. - Vasopressin secretion and thirst are both stimulated by a free H2O deficit and suppressed by a free H2O excess. - Thus, appropriately, the same circumstances that call for reducing urinary output to conserve body H2O give rise to the sensation of thirst to replenish body H2O.

Kidneys role in acid base balance

The kidneys control the pH of body fluids by adjusting three interrelated factors: (1) H+ excretion (2) HCO3 - excretion (3) ammonia (NH3) secretion

Positive Balance

When the gains via input for a substance exceed its losses via output, a positive balance exists. - The result is an increase in the total amount of the substance in the body.

Stable Balance

When total body input of a particular substance equals its total body output, a stable balance exists

Can the ECF pool be further altered?

Yes, for some ECF constituents, the ECF pool is further altered by transferring this specific constituent into or out of storage within the body. - If the body as a whole has a surplus or deficit of a particular stored substance, the storage site can be expanded or partially depleted to maintain the ECF concentration of the substance within homeostatically prescribed limits. - For example, after absorption of a meal, when more glucose is entering the plasma than is being consumed by the cells, the extra glucose can be temporarily stored, in the form of glycogen, in muscle and liver cells. - This storage depot can then be tapped between meals as needed to maintain the plasma glucose level when no new nutrients are being added to the blood by eating.

The kidneys secrete _______ during acidosis to buffer secreted H+.

ammonia. - The energy-dependent H+ carriers in the tubular cells can secrete H+ against a concentration gradient until the tubular fluid (urine) becomes 800 times more acidic than the plasma. - At this point, further H+ secretion stops because the gradient becomes too great for the secretory process to continue. - The kidneys cannot acidify urine beyond a gradient-limited urinary pH of 4.5. - If left unbuffered as free H+, only about 1% of the excess H+ typically excreted daily would produce a urinary pH of this magnitude at normal urine flow rates, and elimination of the other 99% of the usually secreted H+ load would be prevented—a situation that would be intolerable. - For H+ secretion to proceed, most secreted H+ must be buffered in the tubular fluid so that it does not exist as free H+ and, accordingly, does not contribute to tubular acidity. - Bicarbonate cannot buffer urinary H+ as it does H+ in the ECF because HCO3 - is not excreted in the urine simultaneously with H+. (Whichever of these substances is in excess in the plasma is excreted in the urine.) - There are, however, two important urinary buffers: (1) filtered phosphate buffers (2) secreted ammonia.

Metabolic (or nonrespiratory) alkalosis

is a reduction in plasma [H+] caused by a relative deficiency of noncarbonic acids. - This acid-base disturbance is associated with an increase in [HCO3 -], which, in the uncompensated state, is not accompanied by a change in [CO2].

respiratory acidosis

is the result of abnormal CO2 retention arising from hypoventilation. - As less-than-normal amounts of CO2 are lost through the lungs, the resulting increase in CO2 generates more H+ from this source.

Two other minor categories are included in the ECF:

lymph and transcellular fluid. - Lymph is the fluid being returned from the interstitial fluid to the plasma by means of the lymphatic system, where it is filtered through lymph nodes for immune defense purposes. - Transcellular fluid consists of a number of small, specialized fluid volumes, all of which are secreted by specific cells into a particular body cavity to perform some specialized function. - Transcellular fluid includes cerebrospinal fluid (surrounding, cushioning, and nourishing the brain and spinal cord); intraocular fluid (maintaining the shape of and nourishing the eye); synovial fluid (lubricating and serving as a shock absorber for the joints); pericardial, intrapleural, and peritoneal fluids (lubricating movements of the heart, lungs, and intestines, respectively); and the digestive juices (digesting ingested foods).

Hydrogen ions are continually added to the body fluids as a result of:

metabolic activities. - As with any other constituent, input of hydrogen ions must be balanced by an equal output to maintain a constant [H+] in the body fluids. - On the input side, only a small amount of acid capable of dissociating to release H+ is taken in with food, such as the weak citric acid found in oranges. - Most H1 in the body fluids is generated internally from metabolic activities.

Fluctuations in [H1] alter:

nerve, enzyme, and K+ activity.

Secreted H+ that is coupled with HCO3 -reabsorption is

not excreted. - Instead of being excreted, the secreted H+ combines with filtered HCO3 - and ultimately becomes incorporated into reabsorbable H2O molecules. - By contrast, secreted H+ that is excreted is coupled with the addition of new HCO3 - to the plasma. - When all the filtered HCO3 - has been reabsorbed and additional secreted H+ is generated by dissociation of H2CO3, the HCO3 - produced by this reaction diffuses into the plasma as a "new" HCO3 -. - It is termed "new" because its appearance in plasma is not associated with reabsorption of filtered HCO3 -. - Meanwhile, the secreted H+ combines with urinary buffers, especially basic phosphate (HPO4 2-) and is excreted

Respiratory alkalosis

occurs when excessive CO2 is lost from the body as a result of hyperventilation. - When pulmonary ventilation increases out of proportion to the rate of CO2 production, too much CO2 is blown off. - Consequently, less [H+] is formed from this source.

Formula for pH is:

pH = log 1/[H+] ** Two important points should be noted about this formula: 1. Because [H+] is in the denominator, a high [H+] corresponds to a low pH and a low [H+] corresponds to a high pH.The greater the [H+], the larger the number by which 1 must be divided and the lower the pH. 2. Every unit change in pH actually represents a 10-fold change in [H+] because of the logarithmic relationship. A log to the base 10 indicates how many times 10 must be multiplied by itself to produce a given number. For example, the log of 10 = 1, whereas the log of 100 = 2. The number 10 must be multiplied by itself twice to yield 100 (10 x 10 = 100). Numbers less than 10 have logs less than 1. Numbers between 10 and 100 have logs between 1 and 2, and so on. Accordingly, each unit of change in pH indicates a 10-fold change in [H+]. For example, a solution with a pH of 7 has a [H1] 10 times less than that of a solution with a pH of 6 (a 1 pH-unit difference) and 100 times less than that of a solution with a pH of 5 (a 2 pH-unit difference).

The kidneys conserve or excrete HCO3 - depending on the

plasma [H+]. - Before being eliminated by the kidneys, H+ generated from noncarbonic acids is buffered to a large extent by plasma HCO3 -. - Appropriately, therefore, renal handling of acid-base balance also involves adjustment of HCO3 - excretion, depending on the H+ load in the plasma. - The kidneys regulate plasma [HCO3 -] by three interrelated mechanisms: (1) variable reabsorption of filtered HCO3 - back into the plasma in conjunction with H+ secretion (2) variable addition of new HCO3 - to the plasma in conjunction with H+ secretion (3) variable secretion of HCO3 - in conjunction with H1 reabsorption. ** The first two mechanisms of renal handling of HCO3 - are inextricably linked with H+ secretion, primarily by proximal tubular cells and to a lesser extent by Type A intercalated cells. - Every time a H+ is secreted into the tubular fluid, a HCO3 - is simultaneously transferred into the peritubular capillary plasma. - Whether a filtered HCO3 - is reabsorbed or a new HCO3 - is added to the plasma in accompaniment with H+ secretion depends on whether filtered HCO3 - is present in the tubular fluid to react with the secreted H.

Changing the magnitude of any input or output pathways for a given substance can alter its

plasma concentration - To maintain homeostasis, any change in input must be balanced by a corresponding change in output (for example, increased salt intake must be matched by a corresponding increase in salt output in the urine), and conversely, increased losses must be compensated for by increased intake. - Thus, maintaining a stable balance requires control. - However, not all input and output pathways are regulated to maintain balance. - Generally, input of various plasma constituents is poorly controlled or not controlled at all. - We frequently ingest salt and H2O, for example, not because we need them but because we want them, so the intake of salt and H2O is highly variable. Likewise, hydrogen ion (H+) is uncontrollably generated internally and added to the body fluids. - Salt, H2O, and H+ can also be lost to the external environment to varying degrees through the digestive tract (vomiting), skin (sweating), and elsewhere without regard for the salt, H2O, or H+ balance in the body. - Compensatory adjustments in the urinary excretion of these substances maintain the body fluids' volume and salt and acid composition within the extremely narrow homeostatic range compatible with life despite the wide variations in input and unregulated losses of these plasma constituents.

The movement of H2O between plasma and interstitial fluid across capillary walls is governed by:

relative imbalances between capillary blood pressure (a fluid, or hydrostatic, pressure) and colloid osmotic pressure - The net transfer of H2O between the interstitial fluid and the ICF across the cellular plasma membranes occurs as a result of osmotic effects alone. - The hydrostatic pressures of the interstitial fluid and ICF are both extremely low and fairly constant. All cells are freely permeable to H2O.

Deviations in ECF volume accompanying changes in the salt load trigger:

renal compensatory responses that quickly bring the Na+ load and ECF volume back into line. - Na+ is freely filtered at the glomerulus and actively reabsorbed, but it is not secreted by the tubules, so the amount of Na+ excreted in the urine represents the amount of Na+ filtered but not subsequently reabsorbed: sodium excreted = sodium filtered - sodium reabsorbed ** The kidneys accordingly adjust the amount of salt excreted by controlling two processes: (1) the glomerular filtration rate (GFR) and (2) more important, the tubular reabsorption of Na+

Acid-base imbalances can arise from either what 2 types of disturbances?

respiratory or metabolic disturbances. - Deviations from normal acid-base status are divided into four categories, depending on the source and direction of the abnormal change in [H+]. - These categories are 1.) respiratory acidosis 2.) respiratory alkalosis 3.) metabolic acidosis 4.) metabolic alkalosis - Because of the relationship between [H+] and concentrations of the members of a buffer pair, changes in [H+] are reflected by changes in the ratio of [HCO3 -] to [CO2]. - Recall that the normal ratio is 20/1. - Using the Henderson-Hasselbalch equation and with pK being 6.1 and the log of 20 being 1.3, normal pH 5 6.1 + 1.3 = 7.4. - Determinations of [HCO3-] and [CO2] provide more meaningful information about the underlying factors responsible for a particular acid-base status than do direct measurements of [H+] alone.

Control of _________ is primarily important in regulating ECF volume.

salt balance - To maintain salt balance at a set level, salt input must equal salt output, thus preventing salt accumulation or deficit in the body.

acid-base balance

the kidneys help maintain acid-base balance by adjusting the urinary output of hydrogen ion (acid) and bicarbonate ion (base) as needed. - Also contributing to acid-base balance are the buffer systems in the body fluids, which chemically compensate for changes in hydrogen ion concentration, and the lungs, which can adjust the rate at which they excrete hydrogen ion-generating CO2

The respiratory system serves as

the second line of defense against changes in [H+]. - Respiratory regulation acts at a moderate speed, coming into play only when chemical buffer systems alone cannot minimize [H+] changes. - When deviations in [H+] occur, the buffer systems respond immediately, whereas adjustments in ventilation require a few minutes to be initiated. - If a deviation in [H+] is not swiftly and completely corrected by the buffer systems, the respiratory system comes into action a few minutes later, thus serving as the second line of defense against changes in [H+]. - The respiratory system alone can return the pH only 50% to 75% of the way toward normal. - Two reasons contribute to the respiratory system's inability to fully compensate for a nonrespiratory-induced acid-base imbalance. - First, during respiratory compensation for a deviation in pH, the peripheral chemoreceptors, which increase ventilation in response to an elevated arterial [H+], and the central chemoreceptors, which increase ventilation in response to a rise in [CO2] (by monitoring CO2- generated H+ in the brain ECF), work at odds. - Consider what happens in response to acidosis arising from a non respiratory cause. - When the peripheral chemoreceptors detect an increase in arterial [H+], they reflexly stimulate the respiratory center to step up ventilation, causing more acid-forming CO2 to be blown off. - In response to the resultant fall in CO2, however, the central chemoreceptors start to inhibit the respiratory center. - By opposing the action of the peripheral chemoreceptors, the central chemoreceptors stop the compensatory increase in ventilation short of restoring pH all the way to normal. - Second, the driving force for the compensatory increase in ventilation is diminished as the pH moves toward normal. - Ventilation is increased by the peripheral chemoreceptors in response to a rise in arterial [H+], but as the [H+] is gradually reduced by stepped-up removal of H+-forming CO2, the enhanced ventilatory response is also gradually reduced. - When changes in [H+] stem from [CO2] fluctuations that arise from respiratory abnormalities, the respiratory mechanism cannot contribute to pH control. - For example, if acidosis exists because of CO2 accumulation caused by lung disease, the impaired lungs cannot possibly compensate for acidosis by increasing the rate of CO2 removal. - The buffer systems (other than the H2CO3:HCO3 - pair) plus renal regulation are the only mechanisms available for defending against respiratory-induced acid-base abnormalities.

The kidneys are a powerful ...

third line of defense against changes in [H+]. - The kidneys require hours to days to compensate for changes in body-fluid pH, compared to the immediate responses of the buffer systems and the few minutes of delay before the respiratory system responds. - Therefore, they are the third line of defense against [H+] changes in body fluids. - Although not responding as quickly as the other means of pH control, the kidneys are the most potent acid-base regulatory mechanism; they not only can variably remove H+ from any source, but they also can variably conserve or eliminate HCO3 - depending on the acid-base status of the body. - By simultaneously removing acid (H+) from and adding base (HCO3 -) to body fluids, the kidneys are able to restore the pH toward normal more effectively than the lungs, which can adjust only the amount of H- -forming CO2 in the body. - Also contributing to the kidneys' acid-base regulatory potency is their ability to return pH almost exactly to normal. - By comparison to the respiratory system's inability to fully compensate for a pH abnormality, the kidneys can continue to respond to a change in pH until compensation is essentially complete.

Sources of H2O Input

■ In a person's typical daily H2O balance, a little more than a liter of H2O is added to the body by drinking liquids. ■ Surprisingly, an amount almost equal to that is obtained from eating solid food. Muscles consist of about 75% H2O; meat (animal muscle) is therefore 75% H2O. Fruits and vegetables consist of 60% to 96% H2O. Therefore, people normally get almost as much H2O from solid foods as from liquids. ■ The third source of H2O input is metabolically produced H2O. Chemical reactions within cells convert food and O2 into energy, producing CO2 and H2O in the process. This metabolic H2O produced during cell metabolism and released into the ECF averages about 350 mL per day. ** The average H2O intake from these three sources totals 2600 mL per day. Another source of H2O often employed therapeutically is intravenous infusion of fluid.

Compensations for Metabolic Alkalosis

■ In metabolic alkalosis, chemical buffer systems immediately liberate H+. ■ Ventilation is reduced so that extra H+ -generating CO2 is retained in the body fluids. ■ If the condition persists for several days, the kidneys conserve H+ and excrete the excess HCO3 - in the urine. ** The resultant compensatory increase in [CO2] and the partial reduction in [HCO3 -] together restore the [HCO3 -]/[CO2] ratio back to the equivalent of 20/1 at 25/1.25.

Sources of H2O Output

■ On the output side of the H2O balance tally, you lose nearly a liter of H2O daily without being aware of it. This insensible loss (loss of which the person has no sensory awareness) occurs from the lungs and nonsweating skin. During respiration, inspired air becomes saturated with H2O within the airways. This H2O is lost when the moistened air is subsequently expired (see p. 447). Normally, you are not aware of this H2O loss, but you can recognize it on cold days, when H2O vapor condenses so that you can "see your breath." The other insensible loss is continual loss of H2O from the skin even in the absence of sweating. Water molecules can diffuse through skin cells and evaporate without being noticed. Fortunately, the skin is fairly waterproofed by its keratinized exterior layer, which protects against a greater loss of H2O by this avenue (see p. 440). When this protective surface layer is lost, such as when a person has extensive burns, increased fluid loss from the burned surface can cause serious problems with fluid balance. ■ Sensible loss (loss of which the person is aware) of H2O from the skin occurs through sweating, which represents another avenue of H2O output. At an air temperature of 68°F, an average of 100 mL of H2O is lost daily through sweating. Loss of water from sweating can vary substantially, depending on the environmental temperature and humidity and the degree of physical activity; it may range from zero up to as much as several liters per hour in very hot weather. ■ Another passageway for H2O loss from the body is through the feces. Normally, only about 100 mL of H2O are lost this way each day. During fecal formation in the large intestine, most H2O is absorbed out of the digestive tract lumen into the blood, thereby conserving fluid and solidifying the digestive tract's contents for elimination. Additional H2O can be lost from the digestive tract through vomiting or diarrhea. ■ By far the most important output mechanism is urine excretion, with 1500 mL (1.5 liters) of urine being produced daily on average. ** The total H2O output is 2600 mL/day, the same as the volume of H2O input in our example. This balance is not by chance. Normally, H2O input matches H2O output so that the H2O in the body remains in balance.

The influence of acidosis and alkalosis on H+ secretion includes:

■ When the [H+] of the plasma passing through the peritubular capillaries is elevated above normal, the proximal tubular cells and Type A intercalated cells respond by secreting greater-than-usual amounts of H1 from the plasma into the tubular fluid to be excreted in the urine. ■ Conversely, when plasma [H+] is lower than normal, the kidneys conserve H+ by reducing its secretion by proximal cells and Type A intercalated cells. Also, Type B intercalated cells become more active to compensate for alkalosis by increasing H+ reabsorption. Together these actions decrease H+ excretion in the urine. ** Because chemical reactions for H+ secretion begin with CO2, the rate at which they proceed is also influenced by [CO2]. ■ When plasma [CO2] increases, the rate of H+ secretion speeds up. ■ Conversely, the rate of H+ secretion slows when plasma [CO2] falls below normal. - These responses are especially important in renal compensations for acid-base abnormalities involving a change in H2CO3 caused by respiratory dysfunction. Thus, the kidneys can adjust H+ excretion to compensate for changes in both carbonic and noncarbonic acids.