Acid–base balance, or the concentration of H+ in the extracellular fluid (ECF), is tightly regulated, such that the pH of the arterial blood is maintained within a small range, pH 7.37 to 7.42, or [H+] = 40 nmol/L. This is important as pH affects many cellular processes, for example, electrochemical gradients necessary for muscle contraction, transport of substances across membranes, bone mineralization, body fluid balance, optimal enzyme functioning, metabolic processes (e.g., gluconeogenesis and glycolysis), and cell division.
The body continuously produces respiratory (or volatile) acids and metabolic (or fixed) acids. It is able to respond very effectively to perturbations in acid (or base) production by utilizing extracellular and intracellular buffers, by altering ventilation rates, and by altering their renal excretion (Fig. 18.1).
Volatile Acid (Carbon Dioxide)
Volatile acid (carbon dioxide, CO2) is produced from cellular aerobic respiration. CO2 combines with H2O to form carbonic acid (H2CO3), which is catalyzed by the enzyme carbonic anhydrase. H2CO3 then rapidly dissociates to form H+ and HCO3−. This reaction sequence can be expressed as follows:
Note: CO2 itself is not an acid, as it does not contain an H+ ion and therefore cannot act as a proton donor. However, it is designated as a volatile acid, as it has the potential to create H2CO3.
Nonvolatile (Fixed) Acids
Fixed acids are produced from protein catabolism (sulfuric acid, H2SO4), from phospholipid catabolism (phosphoric acid, H3PO4), or from anaerobic carbohydrate catabolism (lactic acid). Fixed acid concentrations may rise during exercise (e.g., lactic acid) or many pathological conditions (e.g., diabetes mellitus may cause ketoacid production).
18.1 Chemical Buffering Systems
Chemical buffers are solutions consisting of a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. Chemical buffers allow only small pH changes when a strong acid or base is added to them. Chemical buffers are able to resist changes in pH due to the equilibrium between the acid (HA) and its conjugate base (A−) as expressed by
HA ↔ H+ + A−
When strong acid is added to a chemical buffer solution consisting of a weak acid and its conjugate base, the equilibrium is shifted to the left, consuming some of the H+ ions of the strong acid and therefore resisting an increase in [H+] of the magnitude that would be expected. Similarly, when a strong alkali is added, the equation shifts to the right, and the [H+] decreases less than would be expected.
Chemical buffering systems act within seconds and are the first line of defense against changes in [H+] and therefore pH.
Extracellular Fluid Buffers
– The most important physiological buffer pair of ECF is HCO3−/CO2. This is due to their high concentration in plasma (24 mM) and its tight regulation: CO2 by the lungs and HCO3− by the kidneys.
Fig. 18.1 Factors affecting blood pH.
Various pH buffers are responsible for maintaining the body at a constant pH. The most important buffer for blood and other body fluids is the bicarbonate/carbon dioxide (HCO3−/CO2) buffer system. The pKa value determines the prevailing concentration ratio of the buffer base and buffer acid ([HCO3−] and [CO2], respectively) at a given pH (Henderson–Hasselbalch equation).The primary function of the HCO3−/CO2 buffer system in blood is to buffer H+ ions. However, this system is especially important because the concentrations of the two buffer components can be modified largely independently of each other: by respiration and by the kidney. Hemoglobin in red blood cells, the second most important buffer in blood, is a nonbicarbonate buffer system.
– The pKa (the negative logarithm of the ionization constant of an acid) of the HCO3−/CO2 buffer pair is 6.1. The buffering power of a buffer system is greatest when its p Ka equals the pH.
– Phosphate contributes little to the buffering capacity of the ECF because of its low concentration. However, phosphate is an important urinary buffer: excess H+ is excreted as H2PO4− (titratable acid; see page 188).
– The pKa of the HPO42−/H2PO4− buffer pair is 6.8.
Intracellular Fluid Buffers
– Organic phosphates, for example, adenosine monophosphate (AMP), adenosine diphosphate (ADP), adenosine triphosphate (ATP), and phosphorylated proteins, are important buffers within intracellular fluid (ICF).
Intracellular Proteins and Hemoglobin
– Proteins have broad-ranged pKa values, so they vary in their buffering capacity.
– Hemoglobin, especially deoxygenated hemoglobin, is a strong ICF buffer.
Because all buffer pairs in plasma are in equilibrium with the same [H+], a change in the buffering capacity of the entire blood buffer system will be reflected by a change in the buffering capacity of only one buffer pair (isohydric principle). The acid–base status or pH of ECF can be evaluated by examining only the bicarbonate buffer system.
Calculating pH Using the Henderson–Hasselbalch Equation
The Henderson–Hasselbalch equation is expressed as follows:
pH = p Ka + log [A−]/[HA]
where pH is −log10 [H+], p Ka is −log10 equilibrium constant, [A−] is the base form of the buffer system (mM), and [HA] is the acid form of the buffer system (mM).
Note: The pKa value determines the prevailing ratio of the buffer base and buffer acid at a given pH. Buffer pairs are most effective when the pKa value is close to the pH (within 1.0 pH).
The pH of ECF containing the HCO3−/CO2 buffer system can be expressed as functions of the buffer pair concentration using the Henderson–Hasselbalch equation:
Note: The proportionality constant between dissolved CO2 and Pco2 (partial pressure of CO2) is 0.03, and Pco2 is 40 mm Hg.
Thus, the maintenance of a normal plasma pH depends on the preservation of the ratio of [HCO3−] to [CO2] in plasma at ~20:1.
Influence of pH on the excretion of weak acids and bases
The ionization state of weak acids and bases, which include several useful drugs, depends on the pH of their environment. A membrane is more permeable to these substances in their nonionized form. As they become concentrated by the removal of water, they are substantially reabsorbed if they are nonionized. At tubular pH values where they are nonionized, relatively more is reabsorbed, and less is excreted. In contrast, at tubular pH values at which they are charged, they remain in the lumen and are excreted. Most weak acids are nonionized when in their protonated form. When the urine is acidic (low pH), which is the normal situation, this favors passive reabsorption and reduced excretion. Thus, for drugs that are weak acids, a low urinary pH reduces the excretion rate. For many weak bases, the influence of urinary pH is just the opposite. When a filtered weak base becomes protonated at low pH, it usually becomes a cation and is trapped in the tubular lumen, and subsequently excreted. Raising the pH keeps weak bases in their neutral form and allows them to be reabsorbed. Therefore, alkalinizing the urine via dietary manipulation helps the body retain drugs that are weak bases.
18.2 Respiratory Regulation of Acid–base Balance
When arterial pH is made more acidic or alkaline, the rate of alveolar ventilation is altered via changes in signals from respiratory chemoreceptors. The resulting hyper- or hypoventilation will change arterial Pco2 in the direction that will return arterial pH toward normal.
18.3 Renal Regulation of Acid–base Balance
The respiratory system alone cannot restore acid–base status to normal. The renal system is needed to restore body HCO3− supplies and to eliminate the buffered acids or bases. This is accomplished by the following:
– Reabsorption of virtually all filtered HCO3− from the tubular lumen into peritubular capillary blood
– Formation of “new” HCO3−
– Excretion of excess H+ from peritubular capillary blood into the tubular lumen via urinary buffers
Reabsorption of Filtered Bicarbonate
The vast majority of HCO3− reabsorption occurs in the proximal tubule.
– H+ is secreted by the proximal tubule cells into the tubular lumen via an Na+−H+ antiporter (NHE-3) (Fig. 18.2). The secreted H+ combines with filtered HCO3− in luminal fluid to form CO2 and H2O (catalyzed by luminal carbonic anhydrase), which diffuse into proximal tubule cells (Fig. 18.3). Within these cells, the reverse reaction occurs. The HCO3− produced is transported across the basolateral membrane of proximal tubule cells and reabsorbed into peritubular capillary blood. The H+ ions are secreted again into luminal fluid.
Fig. 18.2 H+ secretion.
Very large quantities of H+ ions are secreted into the lumen of the proximal tubule (1) by primary active transport via H+ ATPase and by secondary active transport via an electroneutral Na+−H+ antiporter (NHE-3). The luminal pH then decreases from 7.4 (filtrate) to ~6.6. The secreted H+ ion combines with HCO3− to form CO2 and H2O. One OH− ion remains in the cell for each H+ secreted; OH− reacts with CO2 to form HCO3− (accelerated by carbonic anhydrase [CA]). HCO3− leaves the cell for the blood. (2), α-intercalated cells secrete H+ ions via H+−K+ ATPase, allowing luminal pH to drop as low as 4.5. The remaining OH− in the cell reacts with CO2 to form HCO3−, released through the basolateral membrane via the anion exchanger AE1. (NBC3, Na+−bicarbonate cotransporter 3)
Fig. 18.3 HCO3− reabsorption.
The H+ secreted into the lumen of the proximal tubule reacts with ~90% of the filtered HCO3− to form CO2 and H2O. Carbonic anhydrase (CA) anchored in the luminal membrane catalyzes this reaction. CO2 readily diffuses into the cell via water channels (aquaporins). CA then catalyzes the transformation of CO2 + H2O to H+ + HCO3− within the cell. The H+ ions are again secreted into the lumen, while HCO3− exits through the basolateral membrane via an electrogenic Na+−HCO3− cotransporter. Thus, HCO3− is transported through the luminal membrane in the form of CO2 (main driving force: concentration gradient for CO2) and exits the basolateral membrane as HCO3− (main driving force: membrane potential). (NBC, Na+−bicarbonate cotransporter)
Factors Influencing Bicarbonate Reabsorption
Filtered Load of HCO3−
The rate of HCO3− reabsorption from the lumen into peritubular capillary blood increases in proportion to the filtered load of HCO3−. It is possible that high concentrations of HCO3− in the filtrate raise tubular fluid pH, favoring more H+ secretion (via H+−ATPase and Na+−H+ antiporter) and thus more HCO3− reabsorption (as CO2 combines with the additional H+ ions in the lumen and is reabsorbed as HCO3−).
Extracellular Fluid Volume
– Expansion of ECF volume results in decreased Na+ reabsorption from the tubular lumen tubular cells. This decreases Na+-coupled H+ secretion (via Na+−H+ antiporter) from tubular cells into the lumen and thus decreases HCO3−reabsorption.
– Similarly, contraction of ECF volume results in increased Na+ reabsorption, increased H+ secretion, and therefore increased HCO3− reabsorption. This is known as contraction alkalosis and is treated by giving an infusion of NaCl to correct ECF volume contraction and the metabolic alkalosis.
– High arterial Pco2 will increase the rate of HCO3− reabsorption from the lumen into tubular cells because the elevated Pco2 causes an increase in cellular H+ production and secretion.
– Low arterial Pco2 will similarly decrease the rate of HCO3− reabsorption from the tubular lumen into peritubular capillary blood.
Note: The dependence of HCO3− reabsorption on Pco2 allows the kidney to respond to respiratory acidosis and alkalosis.
– High plasma [Cl−] decreases HCO3− reabsorption.
– High plasma [K+] decreases H+ secretion and therefore HCO3− reabsorption.
– Angiotensin II increases H+ secretion (via Na+−H+ antiporter) and HCO3− reabsorption in the proximal tubule; aldosterone has similar effects on the distal nephron. Corticosteroids (e.g., cortisol) will exert mineralocorticoid effects in high concentrations, causing HCO3− reabsorption.
– Parathyroid hormone (PTH) decreases HCO3− reabsorption.
Formation of “New” Bicarbonate
H+ produced within tubular cells is secreted into tubular fluid. The secreted H+ can combine with other non-HCO3− buffers in luminal fluid, namely, phosphates and ammonia (NH3). The H+ ions remain in luminal fluid as part of the buffer pairs and are later excreted. The HCO3− that is formed within renal cells at the same time is then transported across the basolateral membrane into peritubular capillary blood by a Cl−−HCO3− exchanger. Therefore, for every H+ that is secreted and combines with non-HCO3− buffers, a new moiety of HCO3− is formed within renal cells and added to body fluids.
Excretion of Excess H+
Excretion of Excess H+ as Titratable Acid
Titratable acid is acid in the urine formed by the protonation of filtered buffer bases. Its amount can be quantified by titrating urine back to pH 7.4 with a strong base (sodium hydroxide [NaOH]). Secreted H+ ions combine with filtered buffer bases, principally divalent phosphate (HPO42−), to form acids, for example, monovalent phosphate (H2PO4−), which are then excreted, as shown below.
H+ (secreted) + buffer base (filtered) → buffer acid (excreted)
The supply of filtered buffer base available to be protonated is limited and cannot be upregulated. The only means of increasing H+ excretion on filtered buffers is to lower the urinary pH, which converts a higher fraction of the buffer to the protonated form. However, the kidneys cannot produce urine with a pH lower than ~4.4, because H+ ions within the tubular lumen leak back into tubular cells. Therefore, when large amounts of H+ have to be excreted, the kidneys use a different mechanism, namely, ammonium (NH4+).
Excretion of Excess H+ as Ammonium
The metabolism of amino acids by the liver produces urea (mostly) and glutamine (Fig. 18.4). Urea is excreted, but glutamine is reabsorbed by cells of the proximal tubule and metabolized to NH4+ and HCO3−. The HCO3− is returned to the circulation via peritubular capillaries, and the NH4+ is secreted into the luminal fluid. Much of the NH4+ is reabsorbed in the thick ascending limb of the loop of Henle and accumulates in the medullary interstitium. It is then secreted again in the medullary collecting ducts and excreted. The overall process is shown below.
Glutamine (from liver) → NH4+ (excreted) + HCO3− (returned to circulation)
Because NH4+ is a very weak acid (p Ka = 9.2), a small fraction exists as neutral ammonia (NH3), which is relatively permeable. Thus, some NH4+ transport actually consists of NH3 transport in parallel with proton transport, but the end result is the same.
During times of large acid loads, the hepatic production of glutamine is upregulated, thereby increasing the supply of substrate from which the kidneys synthesize NH4+. Large acid loads are therefore excreted chiefly in the form of NH4+.
Fig. 18.4 Secretion and excretion of NH4+↔ NH3.
Excretion of ammonium ions (NH4+ ↔ NH3) is equivalent to H+ disposal and is therefore an indirect form of H+ excretion (1). For every NH4+ excreted by the kidney, one HCO3− is spared by the liver. This is equivalent to one H+ disposed because the spared HCO3− can buffer an H+ ion. The liver utilizes NH4+ and HCO3− to form urea. Thus, one HCO3− less is consumed for each NH4+ that passes from the liver to the kidney and is eliminated in the urine. Before exporting NH4+ to the kidney, the liver incorporates it into glutamate, yielding glutamine; only a small portion reaches the kidneys as free NH4+. In the kidneys, glutamine enters proximal tubule cells by Na+ symport and is cleaved by mitochondrial glutaminase, yielding NH4+ and glutamate (Glu−). Glu− is further metabolized by glutamate dehydrogenase to yield α–ketoglutarate, producing a second NH4+ ion (2). The NH4+ can reach the lumen in two ways: it dissociates within the cell to yield NH3 and H+, allowing NH3 to diffuse into the lumen, where it rejoins the separately secreted H+ ions; or the NHE-3 carrier secretes NH4+ (instead of H+). Once NH4+ has reached the thick ascending loop of Henle, the bumetanide-sensitive Na+−K+−2Cl− cotransporter (BSC) carrier reabsorbs NH4+ (instead of K+) so that it remains in the medulla. Recirculation of NH4+ through the loop of Henle yields a very high concentration of NH4+ ↔ NH3 + H+ toward the papilla (3). While the H+ ions are then actively pumped out into the lumen of the collecting duct (4), the NH3 molecules arrive there by nonionic diffusion and possibly by an NH3 transporter. The NH3 gradient required to drive this diffusion can develop because the low luminal pH (~4.5) leads to a much smaller NH3 concentration in the lumen than in the medullary interstitium, where the pH is about two pH units higher and the NH3 concentration is consequently about 100 times higher than in the lumen.
Under normal conditions, all filtered HCO3− is reabsorbed, and an additional 40 to 60 mmol of acid is excreted in the form of titratable acid and NH4+ per day. This contributes 40 to 60 mmol of new HCO3− to blood and replenishes the HCO3− used to buffer the acid produced from metabolism.
– During acidosis the kidneys compensate by excreting more acidic urine (urine is usually slightly acidic, about pH 6) still completely reabsorbing HCO3− and increasing the excretion of NH4+.
– During alkalosis cell pH rises, providing less driving force for H+ secretion, so less HCO3− is reabsorbed. The unabsorbed HCO3− will alkalinize the urine. Less NH4+ is formed and less acid excreted. Overall, more HCO3− will be eliminated from the body, and the body fluid will become more acidic.
Quantitation of Renal Tubular Acid Secretion and Excretion
– Total rate of H+ secretion = rate of HCO3− reabsorption + rate of titratable acid excretion + rate of NH4+ excretion
–Total rate of H+ excretion = rate of titratable acid excretion + rate of NH4+ excretion = total rate at which “new” HCO3− is added to the blood
18.4 Acid–base Disturbances
Arterial pH < 7.36 is acidosis; arterial pH > 7.44 is alkalosis. The causes of such acid–base disturbances are illustrated in Figs. 18.5 and 18.6.
–Respiratory disturbances change [H+] by a primary change in Pco2 because Pco2 is regulated by the rate of alveolar ventilation.
– Metabolic disturbances primarily change the [HCO3−] by the addition or loss of fixed acids or bases derived from metabolic processes.
The efficiency of compensatory responses is indicated by how close arterial pH is brought back to 7.4. Metabolic disturbances are compensated almost instantaneously. Primary respiratory disturbances require several days for compensation.
Metabolic acidosis results from overproduction or abnormal retention of fixed acids, or from loss of bases.
– Arterial [H+] is increased, and arterial HCO3− is decreased.
– Respiratory compensation for the acidosis involves hyperventilation, which reduces the Pco2.
– Renal compensation involves virtually complete reabsorption of HCO3−, which replenishes that used to buffer the excess acid and an increase in the excretion of titratable acid and NH4+. The availability of titratable acid is very limited, but the kidneys can greatly increase production of NH4+.
Serum anion gap
The serum anion gap represents unmeasured anions in serum. These include sulfates, phosphate, citrate, and proteins.
It is calculated as follows: serum anion gap = (Na+]) – ([Cl−] + [HCO3−]). The normal value of the serum anion gap is 12 mEq/L (range 8–16 mEq/L).The serum anion gap is normal when the loss of HCO3− is almost fully compensated for by an increase in Cl−. This is known as hyperchloremic metabolic acidosis. A high serum anion gap indicates acidosis where the loss of HCO3− (used to buffer the fixed acid) is not compensated by an increase in Cl−. Electroneutrality is maintained by an increase in the levels of unmeasured anions (e.g., ketoacids). A low serum anion gap is usually caused by hypoalbuminemia. Albumin is a negatively charged protein; its loss leads to the retention of HCO3− and Cl−; hence, the anion gap is reduced.
Renal tubular acidosis type1
Renal tubular acidosis(RTA) type1 occurs when the tubules fail to excrete titratable acid and NH4+, and there is a failure to create acidic urine. It presents in childhood with increased urination (polyuria), failure to thrive, and bone pain. Adults present with bone pain (osteomalacia), renal stones, constipation, weakness(due to K+ depletion), or renal failure. Tests will show urine pH>6(normally, urine pH≤6), and there is a normal anion gap. Treatment is with HCO3− and K+ replacement.
Renal tubular acidosis type2
RTA type2 occurs when there is renal loss of HCO3− and serum[HCO3−] falls until the filtered load equals the reduced resorptive capacity, allowing the urine to become acid-ified. It presents in childhood with failure to thrive, metabolic acidosis, and alkaline or slightly acid urine. The anion gap is normal. Treatment is with HCO3− replacement.
Renal tubular acidosis type4
RTA type 4 occurs in diseases associated with aldosterone deficiency(e.g., Addison disease and diabetes mellitus). There is failure to excrete NH4+ because hypokalemia (caused by the aldosterone deficiency) inhibits NH3 synthesis. The anion gap is normal. Treatment (if aldosterone deficient) is with corticosteroid replacement (e.g., fludrocortisone) or a loop diuretic(e.g., furosemide). The underlying disease process should also be treated appropriately.
Acute renal failure
Acute renal failure may occur due to disease of the kidneys themselves, which may be vascular, septic, neoplastic, due to drugs, or due to pregnancy. Extrarenal causes include burns, sepsis, trauma, heart failure, and obstruction. Acute renal failure produces a sharp rise in urea, creatinine, K+(hyperkalemia), and Na+ (hypernatremia) usually with oliguria(low urine output) or anuria (no urine output). There may also be vomiting, confusion, bruising, or gastrointestinal bleeding. A metabolic acidosis (usually with a normal anion gap) will occur due to the failure to excrete H+ as titratable acid and NH4+. Treatment should be aimed at the underlying cause, but hyperkalemia may require urgent correction to avoid cardiac complications.
Metabolic alkalosis results from loss of fixed acids or from excessive intake or retention of bases.
– Arterial [H+] is decreased, and [HCO3−] is increased.
– Respiratory compensation involves hypoventilation causing a rise in Pco2. However, the compensatory rise in Pco2 will tend to increase H+ secretion from peritubular capillary blood into the tubular lumen and HCO3− reabsoption from the tubular lumen into peritubular capillary blood, thereby limiting its effectiveness.
– Renal response involves increased renal excretion of HCO3−.
Respiratory acidosis results from failure of the lungs to adequately expire CO2 due to hypoventilation.
– Arterial Pco2 is increased, which causes an increase in [H+] and [HCO3−].
– There cannot be respiratory compensation for acidosis of respiratory origin.
– Renal compensation includes increased H+ excretion as titratable acid and NH4+, increased HCO3− reabsorption, and production of “new” HCO3−.
Fig. 18.5 Causes of alkalosis.
Metabolic activity may cause the accumulation of organic acids (e.g., lactic acid and ketoacids) (1). One H+ is produced per acid. If these acids are metabolized, H+ disappears again. Consumption of the acids can cause alkalosis. Mobilization of alkaline salts from bone, for example, during immobilization, can cause alkalosis (2). Respiratory alkalosis occurs in hyperventilation (e.g., due to damage to respiratory neurons, high altitude, or salicylate poisoning) (3). Numerous disorders can lead to metabolic alkalosis. In hypokalemia (low blood [K+]), the chemical gradient for K+ across cell membranes is increased. In some cells, this leads to hyperpolarization, which drives more negatively charged HCO3− from the cell. Hyperpolarization, for example, raises HCO3− efflux from the proximal tubule via Na+−HCO3− cotransport (4). The resulting intracellular acidosis stimulates the luminal Na+−H+ exchange and thus promotes H+ secretion, as well as HCO3− production, in the proximal tubule cell. Both processes lead to alkalosis. Aldosterone is released in hypovolemia, stimulating H+ secretion in the distal nephron (5). Thus, the kidney’s ability to eliminate HCO3− is compromised, resulting in alkalosis. In vomiting of stomach contents, the body loses H+(6). What is left behind is the HCO3− produced when HCl is secreted in parietal cells. Normally, the HCO3− formed in the stomach is reused in the duodenum to neutralize the acidic stomach contents and only transiently leads to a weak alkalosis. In liver failure, hepatic production of urea is decreased, the liver uses up less HCO3−, and alkalosis develops (7). Reduced protein breakdown, for example, as a result of a protein- deficient diet, reduces the metabolic formation of H+ and thus favors the development of alkalosis (8).
Fig. 18.6 Causes of acidosis.
Acidosis can develop when there is increased formation or decreased breakdown of organic acids (1). One H+ is produced per acid. Mineralization of bone favors the development of acidosis (2). Many primary and secondary diseases of the respiratory system, as well as abnormal regulation of breathing, can lead to respiratory acidosis (3). In hyperkalemia (elevated blood K+ levels), the chemical gradient across the cell membrane is reduced (4). The resulting depolarization diminishes the electrical driving force for HCO3− transport out of the cell. It slows the efflux of HCO3− in the proximal tubules via Na+−HCO3− cotransport. The resulting intracellular acidosis inhibits the luminal Na+/H+ exchange and thus impairs H+ secretion as well as HCO3− production in the proximal tubule cells. Both processes lead to acidosis. Hypoaldosteronism reduces the renal excretion of H+and HCO3− production (5). Diarrhea causes a loss of HCO3− from the gut (6). The liver requires two HCO3− ions when incorporating two molecules of NH4+ in the formation of urea; thus, increased urea production can lead to acidosis (7). A protein-rich diet promotes the development of acidosis as amino acid breakdown generates H+ ions (8).
Respiratory alkalosis results from excessive loss of CO2 due to hyperventilation. Anxious p atients presenting with hyperventilation can be treated by having them rebreathe into a paper bag.
– Arterial PCO2 is decreased, which causes a decrease in [H+] and [HCO3−].
– There cannot be respiratory compensation for alkalosis of respiratory origin.
– Renal compensation includes decreased excretion of H+ as titratable acid and NH4+ and decreased HCO3− reabsorption.
Table 18.1 summarizes acid–base disturbances and their compensation/correction.