ACID BASE BALANCE

Feghiu Iuliana, Tacu Lilia

Metabolic activities of the body require precise regulation of acid-base balance, which is
reflected in the pH of the ECF. Membrane excitability, enzyme systems, and chemical reactions all depend on
the pH being regulated within a narrow physiologic range to function in an optimal way. Many conditions,
pathologic or otherwise, can alter acid-base balance.
Normally, the concentration of body acids and bases is regulated so that the pH of extracellular body
fluids is maintained within a very narrow range of 7.35 to 7.45. This balance is maintained through mechanisms
that generate, buffer, and eliminate acids and bases.
Mechanisms of acid-base balance
■ The pH is determined by the ratio of the bicarbonate (HCO 3-) base to the volatile carbonic acid
(H2CO3 → H++ HCO3-). At a normal pH of 7.4, the ratio is 20:1.
■ The pH is regulated by extracellular (carbonic acid [H 2CO3]/bicarbonate [HCO3-]) and intracellular
(proteins) systems that buffer changes in pH that would otherwise occur because of the metabolic production of
volatile (CO2) and nonvolatile (i.e., sulfuric and phosphoric) acids.
■ The respiratory system regulates the concentration of the volatile carbonic acid (CO 2-+ H2O →H2CO3
→ H+ + HCO3-) by changing the rate and depth of respiration.
■ The kidneys regulate the plasma concentration of HCO 3- by two processes: reabsorption of the filtered
HCO3- and generation of new HCO 3- or the elimination of H+ ions that have been buffered by tubular systems
(phosphate and ammonia) to maintain a luminal pH of at least 4.5.
Acid-base chemistry
An acid is a molecule that can dissociate and release a hydrogen ion (H +) and a base is an ion or
molecule that can accept or combine with H +. For example, hydrochloric acid (HCl) dissociates in water to
form H- and Cl- ions. The bicarbonate ion (HCO3-) is a base because it can combine with H + to form carbonic
acid (H2CO3). Most of the body’s acids and bases are weak acids and bases, the most important being H 2CO3,
which is a weak acid derived from carbon dioxide (CO 2 bicarbonate HCO3-, which is a weak base.
The concentration of H- in body fluids is low compared with other ions. For example, the Na + is present
at a concentration approximately 3.5 million times that of the H -. Because it is cumbersome to work with such a
small number, the H+ concentration is commonly expressed in terms of the pH. Specifically, pH represents the
negative logarithm (log10) of the H+ concentration expressed in mEq/L. Thus, a pH value of 7.0 implies an H -
concentration of 10-7 (0.0000001 mEq/L). Since the pH is inversely related to the H + concentration, a low pH
indicates a high concentration of H + and a high pH a low concentration of H +. Acids and bases exist as buffer
pairs or systems - a mixture of a weak acid and its conjugate base or a weak base and its conjugate acid. When
an acid (HA) is added to water, it dissociates reversibly to form H + and its conjugate anion (A-). The degree to
which an acid dissociates and acts as an H + donor determines whether it is a strong or weak acid. Strong acids,
such as sulfuric acid, dissociate completely, whereas weak acids, such as acetic acid, dissociate only to a limited
extent. The same is true of a base and its ability to dissociate and accept a H +.
Acid and base production
Acids are continuously generated as by-products of metabolic processes. Physiologically, these acids
fall into two groups: the volatile H2CO3 acid and all other nonvolatile or fixed acids (Fig.1). The difference
between the two types of acids arises because H 2CO3 is in equilibrium with CO2 (H2CO3 → CO2 + H2O), which
is volatile and leaves the body by way of the lungs. Therefore, the H 2CO3 concentration is determined by the
lungs and their capacity to exhale CO 2. The fixed or nonvolatile acids (e.g., sulfuric, hydrochloric, phosphoric)
are not eliminated by the lungs. Instead, they are buffered by body proteins or extracellular buffers, such as
HCO3-, and then eliminated by the kidney.
Carbon dioxide and bicarbonate production.
Carbon dioxide, which is the end product of aerobic metabolism, is transported in the circulation as a
dissolved gas (i.e., PCO2), as the bicarbonate ion (HCO 3-), or as carbaminohemoglobin in CO 2 bound to
hemoglobin. Collectively, dissolved CO 2 and HCO3- account for approximately 77% of the CO 2 that is
transported in the extracellular fluid; the remaining CO 2 travels as carbaminohemoglobin. Although CO 2 is a
gas and not an acid, a small percentage of the gas combines with water to form H 2CO3. The reaction that
generates H2CO3 from CO2 and water is catalyzed by an enzyme called carbonic anhydrase, which is present in
large quantities in red blood cells, renal tubular cells, and other tissues in the body. The rate of the reaction
between CO2 and water is increased approximately 5000 times by the presence of carbonic anhydrase. Were it
not for this enzyme, the reaction would occur too slowly to be of any significance Because it is almost
impossible to measure H2CO3, CO2 measurements are commonly used when calculating pH.

Fig. 1. The maintenance of normal blood pH by chemical buffers, the respiratory system, and the kidneys. On a
mixed diet, pH is threatened by the production of strong acids (sulfuric, hydrochloric, and phosphoric) mainly as the result
of protein metabolism. These strong acids are buffered in the body by chemical buffer bases such as extracellular fluid
(ECF) bicarbonate (HCO3-). The respiratory system disposes of carbon dioxide (CO2). The kidney eliminates hydrogen
ions (H-) combined with urinary buffers and anions in the urine. At the same time, they add new HCO3- to the ECF to
replace the HCO3- consumed in buffering strong acids.
(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

The H2CO3 content of the blood can be calculated by multiplying the partial pressure of CO 2 (PCO2) by
its solubility coefficient, which is 0.03. This means that the concentration of H 2CO3 in the arterial blood, which
normally has a PCO2 of approximately 40 mm Hg, is 1.20 mEq/ L (40× 0.03 = 1.20), and that for venous blood,
which normally has a PCO2 of approximately 45 mm Hg, is 1.35 mEq/L.
Production of fixed or nonvolatile acids and bases
The metabolism of dietary proteins and other substances results in the generation of fixed or nonvolatile
acids and bases. Oxidation of the sulfur-containing amino acids (e.g., methionine, cysteine) results in the
production of sulfuric acid; arginine and lysine, hydrochloric acid; and phosphorus-containing nucleic acids,
phosphoric acid. Incomplete oxidation of glucose results in the formation of lactic acid, and incomplete
oxidation of fats, the production of ketoacids. The major source of base is the metabolism of amino acids such
as aspartate and glutamate and the metabolism of certain organic anions (e.g., citrate, lactate, acetate). Acid
production normally exceeds base production, with the net effect being the addition of approximately 1
mmol/kg body weight of nonvolatile or fixed acid to the body each day. Consumption of a vegetarian diet,
which contains large amounts of organic anions, results in the net production of base.
Carbon dioxide transport
Body metabolism results in a continuous production of carbon dioxide (CO 2). As CO2 is formed during
the metabolic process, it diffuses out of body cells into the tissue spaces and then into the circulation. It is
transported in the circulation in three forms: (1) dissolved in the plasma, (2) as bicarbonate, and (3) attached to
hemoglobin
 Plasma. A small portion (about 10%) of the CO 2 that is produced by body cells is transported in the
dissolved state to the lungs and then exhaled. The amount of dissolved CO 2 that can be carried in plasma is
determined by the partial pressure of the gas (PCO 2) and its solubility coefficient (0.03 mL/100 mL plasma for
each 1 mm Hg PCO2). Thus, each 100 mL of arterial blood with a PCO 2 of 40 mm Hg would contain 1.2 mL of
dissolved CO2. It is the carbonic acid (H2CO3) formed from hydration of dissolved CO 2 that contributes to the
pH of the blood.

Bicarbonate. Carbon dioxide in excess of that which can be carried in the plasma moves into the red
blood cells, where the enzyme carbonic anhydrase (CA) catalyzes its conversion to carbonic acid (H 2CO3). The
H2CO3, in turn, dissociates into hydrogen (H +) and bicarbonate (HCO3-) ions. The H+ combines with
hemoglobin and the HCO3- diffuses into plasma, where it participates in acid-base regulation. The movement of
HCO3- into the plasma is made possible by a special transport system on the red blood cell membrane in which
HCO3- ions are exchanged for chloride ions (Cl-).

Hemoglobin. The remaining CO2 in the red blood cells combines with hemoglobin to form
carbaminohemoglobin (HbCO2). The combination of CO2 with hemoglobin is a reversible reaction
characterized by a loose bond, so that CO2 can be easily released in the alveolar capillaries and exhaled from the
lung.

Calculation of pH
The serum pH can be calculated using an equation called the Henderson-Hasselbalch equation. This
equation uses the dissociation constant for the bicarbonate buffer system and the HCO 3- to PCO2 (used as a
measure of H2CO3) ratio (Fig.2). Because the ratio is used, a change in HCO3- will have little or no effect on pH
as long as there is an accompanying change in PCO 2. Likewise, a change in PCO 2 will have little effect on pH
as long as there is an accompanying change in HCO 3-.
 Fig. 2. Normal and compensated states of pH and acid-base balance represented as a balance scale.
(A) When the ratio of bicarbonate (HCO3-) to carbonic acid (H2CO3, arterial CO2 _ 0.03) - 20:1, the pH _ 7.4. (B) Metabolic
acidosis with a HCO3- :H2CO3 ratio of 10:1 and a pH of 7.1. (C) Respiratory compensation lowers the H2CO3 to 0.6
mEq/L and returns the HCO3- :H2CO3 ratio to 20:1 and the pH to 7.4. (D) Respiratory alkalosis with a HCO3- :H2CO3
ratio of 40:1 and a pH of 7.7. (E) Renal compensation eliminates HCO3-, reducing serum levels to 12 mEq/L and
returning the HCO3- :H2CO3 ratio to 20:1 and the pH to 7.4. Normally, these compensatory mechanisms are capable of
buffering large changes in pH but do not return the pH completely to normal as illustrated here.
(B) (From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

Regulation of pH. The pH of body fluids is regulated by three major mechanisms: (1) chemical buffer
systems in body fluids, which immediately combine with excess acids or bases to prevent large changes in pH;
(2) the lungs, which control the elimination of CO 2; and (3) the kidneys, which eliminate H + and both reabsorb
and generate HCO3- (see Fig.1).
Chemical buffer systems. The moment-by-moment regulation of pH depends on chemical buffer
systems of the ICF and ECF. As previously discussed, a buffer system consists of a weak base and conjugate
acid pair. In the process of preventing large changes in pH, the system trades a strong acid for a weak acid or a
strong base for a weak base. The three major buffer systems that protect the pH of body fluids are the
bicarbonate buffer system, the transcellular hydrogen potassium exchange system, and body proteins. Bone
provides an additional buffering of body acids. These buffer systems are immediately available to combine with
excess acids or bases and prevent large changes in pH from occurring during the time it takes for the respiratory
and renal mechanisms to become effective.
The bicarbonate buffer system, which is the principal ECF buffer, uses H 2CO3 as its weak acid and a
bicarbonate salt such as sodium bicarbonate (NaHCO 3) as its weak base. It substitutes the weak H 2CO3 for a
strong acid such as hydrochloric acid (HCL+ NaHCO 3 →H2CO3 + NaCl) or the weak bicarbonate base for a
strong base such as sodium hydroxide (NaOH + H 2CO3 →NaHCO3 + H2O). The bicarbonate buffer system is a
particularly efficient system because its components can be readily added or removed from the
body.Metabolism provides an ample supply of CO2, which can replace any H2CO3 that is lost when excess base
is added, and CO2 can be readily eliminated when excess acid is added. Likewise, the kidney can conserve
or form new HCO3- when excess acid is added, and it can excrete HCO3- when excess base is added.
 The transcellular hydrogen/potassium exchange system provides another important system for
regulation of acid-base balance. Both H + and K +are positively charged, and both ions move freely between the
ICF and ECF compartments. When excess H+ is present in the ECF, it moves into the ICF in exchange for K +,
and when excess K+ is present in the ECF, it moves into the ICF in exchange for H +. Thus, alterations in
potassium levels can affect acid-base balance, and changes in acid-base balance can influence potassium levels.
Potassium shifts tend to be more pronounced in metabolic acidosis than in respiratory acidosis.
Proteins are the largest buffer system in the body. Proteins are amphoteric, meaning that they can
function either as acids or bases. They contain many ionizable groups that can release or bind H +. The protein
buffers are largely located in cells, and H - ions and CO2 diffuse across cell membranes for buffering by
intracellular proteins. Albumin and plasma globulins are the major protein buffers in the vascular compartment.
Bone represents an additional source of acid-base buffering. Excess H + ions can be exchanged for Na +
and K+ on the bone surface, and dissolution of bone minerals with release of compounds such as sodium
bicarbonate (NaHCO3) and calcium carbonate (CaCO 3) into the ECF can be used for buffering excess acids. It
has been estimated that as much as 40% of buffering of an acute acid load takes place in bone. The role of bone
buffers is even greater in the presence of chronic acidosis. The consequences of bone buffering include
demineralization of bone and predisposition to development of kidney stones due to increased urinary excretion
of calcium. Persons with chronic kidney disease are at particular risk for reduction in bone calcium due to acid
retention.
Respiratory control mechanisms
The second line of defense against acid-base disturbances is the control of CO 2 by the lungs (Fig.3).
Increased ventilation decreases PaCO 2, while decreased ventilation increases PaCO 2. Chemoreceptors in the
brain stem and the peripheral chemoreceptors in the carotid and aortic bodies sense changes in the PaCO 2 and
pH of the blood and alter the ventilatory rate. The respiratory control of pH is rapid, occurring within minutes,
and is maximal within 12 to 24 hours. Although the respiratory response is rapid, it does not completely return
the pH to normal. It is only about 50% to 75% effective as a buffer system.

Fig. 3. Role of the lung in pH balance (From Despopoulos, Color Atlas of Physiology, 2003)
Renal control mechanisms. The kidneys regulate the pH of the ECF through three major mechanisms:
(1) elimination of H+ in the urine, (2) reabsorption of filtered HCO 3 -, and (3) production of new bicarbonate.
The renal mechanisms for regulating acid-base balance cannot adjust the pH within minutes, as respiratory
mechanisms can, but they continue to function for days until the pH has returned to normal or the near-normal
range.
Hydrogen/bicarbonate exchange. The hydrogen/bicarbonate exchange system regulates pH by
secretion of excess H+ and reabsorption of HCO3- by the renal tubules. Bicarbonate is freely filtered in the
glomerulus (approximately 4300 mEq/day) and reabsorbed or reclaimed in the tubules. Each HCO 3 - that is
reclaimed requires the secretion of H -, a process that is tightly coupled with sodium reabsorption (Fig.4).
Bicarbonate reabsorption also requires the presence of carbonic anhydrase to catalyze the combination of CO 2
and H2O to form H2CO3. Carbonic anhydrase is present both intracellularly as well as on the tubular surface,
allowing secreted H+ to combine with HCO3 - in the tubular fluid to form H2CO3. The H2CO3 rapidly dissociates
to form CO2 and H2O that can readily cross the tubular cell membrane. Inside the tubular cell, carbonic
anhydrase again catalyzes the formation of H 2CO3, which subsequently dissociates into HCO 3- and H+. The
HCO3- then leaves the tubular cell and enters the ECF, and the H + is secreted into the tubular fluid to begin
another cycle of HCO3- reclamation.

Fig. 4. Hydrogen ion (H+) secretion and bicarbonate ion (HCO3-) reabsorption in a renal tubular cell. Carbon dioxide
(CO2) diffuses from the blood or urine filtrate into the tubular cell, where it combines with water in a carbonic anhydrase
(CA) catalyzed reaction that yields carbonic acid (H2CO3). The H2CO3 dissociates to form H+ and HCO3-. The H+ is
secreted into the tubular fluid in exchange for the sodium ion (Na+). The Na+ and HCO3-_enter the extracellular fluid.
(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

Reabsorption of bicarbonate via chloride/bicarbonate exchange. Another mechanism that the

kidney uses in regulating HCO3- is the chloride/bicarbonate anion exchange that occurs in association with Na +
reabsorption. Chloride is absorbed along with Na + throughout the tubules. In situations of volume depletion due
to vomiting and chloride depletion, the kidney is forced to substitute HCO 3- for the Cl- anion, thereby increasing
its absorption of HCO3-. Hypochloremic alkalosis refers to an increase in pH induced by excess HCO 3-
reabsorption due to a decrease in Cl - levels, and hyperchloremic acidosis to a decrease in pH because of
decreased HCO3- reabsorption due to an increase in Cl- levels.
Potassium/hydrogen exchange. The potassium/hydrogen exchange system substitutes the reabsorption
of K for secretion of H+ in the kidney. Hypokalemia is a potent stimulus for H +secretion and HCO3-
+

reabsorption. When serum K+ levels fall, there is movement of K+ from the ICF into the ECF compartment and
a reciprocal movement of H+ from the ECF into the ICF compartment. A similar process occurs in the distal
tubules of the kidney, where the Na+/K+-ATPase exchange pump actively reabsorbs K+ as well as secreting H+.
Acidosis tends to increase H+ elimination and decrease K+ elimination, with a resultant increase in serum
potassium levels, whereas alkalosis tends to decrease H + elimination and increase K + elimination, with a
resultant decrease in serum potassium levels. Aldosterone also influences H + elimination by the kidney. It acts
in the collecting duct to indirectly stimulate the secretion of H + into the urine filtrate while promoting extensive
Na+ reabsorption. This increased secretion of H + leads to increased excretion by the kidney and, therefore,
metabolic acidosis.
Phosphate and ammonia buffers. Because an extremely acidic urine filtrate would be damaging to
structures in the urinary tract, the elimination of H+
requires a buffering system. There are two important intratubular buffer systems: the phosphate buffer system
and the ammonia buffer system (Fig. 5 and Fig. 6).
 The phosphate buffer system (Fig. 5) uses HPO42- and H2PO4- that are present in the tubular filtrate to
buffer H+. The combination of H+ with HPO42- to form H2PO4- allows the kidneys to increase their secretion of
H+ ions. Because HPO42- and H2PO4- are poorly absorbed, they become more concentrated as they move through
the tubules.

Fig. 5. The renal phosphate buffer system.

The monohydrogen phosphate ions (HPO42-) enters the renal tubular fluid in the glomerulus. An H + combines
with the HPO42- to form H2PO4- and is then excreted into the urine in combination with Na +. The HCO3- moves
into the extracellular fluid along with the Na + that was exchanged during secretion of the H+. ( CA – carbonic
anhydrase); (From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .
Another important but more complex buffer system that facilitates the excretion of H + and generation of
new HCO3- is the ammonia buffer system (Fig. 6). Renal tubular cells are able to use the amino acid glutamine
to synthesize ammonia (NH3) and secrete it into the tubular fluid. Hydrogen ions then combine with the NH3 to
form ammonium ions (NH4+). The NH4+ ions, in turn, combine with Cl- ions that are present in the tubular fluid
to form ammonium chloride (NH4Cl), which is then excreted in the urine. One of the most important features of
the ammonia buffer system is that it is subject to physiologic control. Under normal conditions, the amount of
H+ ion eliminated by the ammonia buffer system is about 50% of the acid excreted and new HCO 3- regenerated.
However, with chronic acidosis, it can become the dominant mechanism for H + excretion and new HCO3-
generation.

Fig. 6. The ammonia buffer system.

(A) Glutamine is metabolized in the proximal tubule to produce two NH 4+ and two bicarbonate ions (HCO3-).
The two NH4+ are secreted into the tubular fluid and the two HCO3-, which represent the new HCO3- are returned
to the circulation. (B) A significant portion of secreted NH 4+ is reabsorbed in the medullary interstitium, where
it exist as both NH4+ and NH3.. (C) The NH3 diffuses into the tubular fluid of the collecting tubule, where it
interacts with secrete H+ to form NH4+, which is eliminated in the urine. For each NH4+ excreted in the urine,
 another HCO3- is returned to the circulation. (CA – carbonic anhydrase). (From C. Porth and G. Matfin;
Pathophysiology. Concepts of altered health states).

Laboratory tests
Laboratory tests that are used in assessing acid-base balance include arterial blood gases and pH, CO 2
content and HCO3- levels, base excess or deficit, and blood and urine anion gaps. Although useful in
determining whether acidosis or alkalosis is present, the pH measurements of the blood provide little
information about the cause of an acid-base disorder. Arterial blood gases provide a means of assessing the
respiratory component of acid-base balance. H 2CO3 levels are determined from arterial PaCO 2 levels and the
solubility coefficient for CO2 (normal arterial PaCO2 is 38 to 42 mm Hg). Arterial blood gases are used because
venous blood gases are highly variable, depending on metabolic demands of the various tissues that empty into
the vein from where the sample is being drawn. Laboratory measurements of electrolytes include CO 2 content
and measurement of bicarbonate. These measurements are determined by adding a strong acid to a blood
sample and measuring the amount of CO 2 that is produced. More than 70% of the CO 2 in the blood is in the
form of bicarbonate. The serum bicarbonate is then determined from the total CO 2 content of the blood. Base
excess or deficit is a measure of the HCO3 - excess or deficit. It describes the amount of a fixed acid or base that
must be added to a blood sample to achieve a pH of 7.4 (normal - 2.0 mEq/L).64 A base excess indicates
metabolic alkalosis, and a base deficit indicates metabolic acidosis.
The anion gap describes the difference between the serum concentration of the major measured cation
(Na ) and the sum of the measured anions (Cl - and HCO3-). This difference represents the concentration of
+

unmeasured anions, such as phosphates, sulfates, organic acids, and proteins (Fig.6). Normally, the anion gap
ranges between 8 and 12 mEq/L (a value of 16 mEq/L is normal if both Na + and K+ concentrations are used in
the calculation). The anion gap is increased in conditions such as lactic acidosis and ketoacidosis that result in a
decrease in HCO3-, and it is normal in hyperchloremic acidosis, where Cl - replaces the normal HCO3- anion.

Fig. 7. The anion gap in acidosis due to excess metabolic acids and excess serum chloride levels.
Unmeasured anions such as phosphates, sulfates, and organic acids increase the anion gap because they replace
bicarbonate. This assumes there is no change in sodium content.
(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

DISORDERS OF ACID-BASE BALANCE

The terms acidosis and alkalosis describe the clinical conditions that arise as a result of
changes in dissolved CO2 and HCO3- concentrations. An alkali represents a combination of one or
more alkali metals such as sodium or potassium with a highly basic ion such as a hydroxyl ion (OH -).
Sodium bicarbonate (NaHCO3) is the main alkali in the extracellular fluid. Although the definitions
differ somewhat, the terms alkali and base are often used interchangeably. Hence, the term alkalosis
has come to mean the opposite of acidosis.
Metabolic versus respiratory acid-base disorders
There are two types of acid-base disorders: metabolic and respiratory (Table 1).
Metabolic disorders produce an alteration in the serum HCO3- concentration and results from
the addition or loss of nonvolatile acid or alkali to or from the extracellular fluids. A reduction in pH
due to a decrease in HCO3- is called metabolic acidosis, and an elevation in pH due to increased HCO 3-
levels is called metabolic alkalosis. Respiratory disorders involve an alteration in the PaCO2, reflecting
an increase or decrease in alveolar ventilation. Respiratory acidosis is characterized by a decrease in
pH, reflecting a decrease in ventilation and an increase in PaCO 2. Respiratory alkalosis involves an
increase in pH, resulting from an increase in alveolar ventilation and a decrease in PaCO2.
 Fig. 8. Causes of acidosis
(From S. Silbernagl and F. Lang; Color Atlas of Pathophysiology).
 Fig. 9. Causes of alkalosis
(From S. Silbernagl and F. Lang; Color Atlas of Pathophysiology).
 Primary versus compensatory changes in pH. Acidosis and alkalosis typically involve a
primary or initiating event and a compensatory or adaptive state that results from homeostatic
mechanisms that attempt to correct or prevent large changes in pH. For example, a person may have a
primary metabolic acidosis as a result of overproduction of ketoacids and respiratory alkalosis because
of a compensatory increase in ventilation (see Table 1). Compensatory mechanisms provide a means
to control pH when correction is impossible or cannot be immediately achieved. Often, compensatory
mechanisms are interim measures that permit survival while the body attempts to correct the primary
disorder. Compensation requires the use of mechanisms that are different from those that caused the
primary disorder. For example, the lungs cannot compensate for respiratory acidosis that is caused by
lung disease, nor can the kidneys compensate for metabolic acidosis that occurs because of chronic
kidney disease. The body can, however, use renal mechanisms to compensate for respiratory-induced
changes in pH, and it can use respiratory mechanisms to compensate for metabolically induced
changes in acid-base balance. Because compensatory mechanisms become more effective with time,
there are often differences between the level of pH change that is present in acute and chronic acid-
base disorders.
Single versus mixed acid-base disorders
Thus far we have discussed acid-base disorders as if they existed as a single primary disorder
such as metabolic acidosis, accompanied by a predicted compensatory response (i.e., hyperventilation
and respiratory alkalosis). It is not uncommon, however, for persons to present with more than one
primary disorder or a mixed disorder. For example, a person may present with a low serum HCO 3-
concentration due to metabolic acidosis and a high PCO 2 due to chronic lung disease. Values for the
predicted renal or respiratory compensatory responses can be used in the diagnosis of these mixed
acid-base disorders (Table 1). If the values for the compensatory response fall outside the predicted
values, it can then be concluded that more than one disorder (i.e., a mixed disorder) is present. Since
the respiratory response to changes in HCO 3- occurs almost immediately, there is only one predicted
compensatory response for primary metabolic acid-base disorders. This is in contrast to the primary
respiratory disorders, which have two ranges of predicted values, one for the acute and one for the
chronic response. Renal compensation takes several days to become fully effective. The acute
compensatory response represents the HCO3- levels before renal compensation has occurred and the
chronic response after it has occurred. Thus, the values for the serum pH tend to be more normal in the
chronic phase.
Tab. 1. Summary of single acid-base disturbances and their compensatory responses
(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

METABOLIC ACIDOSIS
 Metabolic acidosis involves a decreased serum HCO3- concentration along with a decrease in
pH. In metabolic acidosis, the body compensates for the decrease in pH by increasing the respiratory
rate in an effort to decrease PaCO2 and H2CO3 levels. The PCO2 can be expected to fall by 1 to 1.5 mm
Hg for each 1 mEq/L fall in HCO3- (Fig. 8).
Metabolic acidosis can be caused by one or more of the following four mechanisms: (1)
increased production of fixed metabolic acids or ingestion of fixed acids such as salicylic acid, (2)
inability of the kidneys to excrete the fixed acids produced by normal metabolic processes, (3)
excessive loss of bicarbonate via the kidneys or gastrointestinal tract (excretory acidosis), or (4) an
increased serum Cl- concentration.
The anion gap is often useful in determining the cause of the metabolic acidosis (Table 2). The
presence of excess metabolic acids produces an increase in the anion gap as sodium bicarbonate is
replaced by the sodium salt of the offending acid (e.g., sodium lactate). When the acidosis results from
an increase in serum Cl- levels (e.g., hyperchloremic acidosis), the anion gap remains within normal
levels.
Increased production of metabolic acids. Among the causes of metabolic acidosis are an
accumulation of lactic acid and excess production of ketoacids. Acute lactic acidosis, which is one of
the most common types of metabolic acidosis, develops when there is excess production or diminished
removal of lactic acid from the blood. Lactic acid is produced by the anaerobic metabolism of glucose.
Most cases of lactic acidosis are caused by inadequate oxygen delivery, as in shock or cardiac arrest.
Such conditions not only increase lactic acid production, but also tend to impair lactic acid clearance
because of poor liver and kidney perfusion. Lactic acidosis can also occur during periods of intense
exercise in which the metabolic needs of the exercising muscles outpace their aerobic capacity for
production of ATP, causing them to revert to anaerobic metabolism and the production of lactic acid.
Lactic acidosis is also associated with disorders in which tissue hypoxia does not appear to be present.
It has been reported in patients with leukemia, lymphomas, and other cancers; those with poorly
controlled diabetes; and persons with severe liver failure. Mechanisms causing lactic acidosis in these
conditions are poorly understood. Some conditions such as neoplasms may produce local increases in
tissue metabolism and lactate production or they may interfere with blood flow to noncancerous cells.
Ketoacids (i.e., acetoacetic and hydroxybutyric acid), produced in the liver from fatty acids, are the
source of fuel for many body tissues. An overproduction of ketoacids occurs when carbohydrate stores
are inadequate or when the body cannot use available carbohydrates as a fuel. Under these conditions,
fatty acids are mobilized from adipose tissue and delivered to the liver, where they are converted to
ketones. Ketoacidosis develops when ketone production by the liver exceeds tissue use. The most
common cause of ketoacidosis is uncontrolled diabetes mellitus, in which an insulin deficiency leads
to the release of fatty acids from adipose cells with subsequent production of excess ketoacids.
Ketoacidosis may also develop as the result of fasting or food deprivation, during which the lack of
carbohydrates produces a self-limited state of ketoacidosis.

Table 2. The anion gap in differential diagnosis of metabolic acidosis

 (From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .

Decreased renal function. Chronic kidney disease is the most common cause of chronic
metabolic acidosis. The kidneys normally conserve HCO3- and secrete H+ ions into the urine as a
means of regulating acid-base balance. In chronic kidney disease, there is loss of both glomerular and
tubular function, with retention of nitrogenous wastes and metabolic acids. In a condition called renal
tubular acidosis, glomerular function is normal, but the tubular secretion of H+ or reabsorption of
HCO3- is abnormal.
Increased bicarbonate losses (excretory acidosis). Increased HCO3- losses occur with the loss
of bicarbonate-rich intestinal secretions which have a high HCO 3- concentration. Consequently,
excessive loss of HCO3- occurs with severe diarrhea; small-bowel, pancreatic, or biliary fistula
drainage; ileostomy drainage; and intestinal suction. In diarrhea of microbial origin, HCO 3- is also
secreted into the bowel as a means of neutralizing the metabolic acids produced by the
microorganisms causing the diarrhea.
Hyperchloremic acidosis. Hyperchloremic acidosis occurs when Cl- levels are increased.
Because Cl- and HCO3- are exchangeable anions, the serum HCO 3- decreases when there is an increase
in Cl-. Hyperchloremic acidosis can occur as the result of abnormal absorption of Cl - by the kidneys or
as a result of treatment with chloride-containing medications (i.e., sodium chloride, amino acid–
chloride hyperalimentation solutions, and ammonium chloride). The administration of intravenous
sodium chloride or parenteral hyperalimentation solutions that contain an amino acid – chloride
combination can cause acidosis in a similar manner. With hyperchloremic acidosis, the anion gap
remains within the normal range, while serum Cl- levels are increased and HCO3- levels are decreased.
Manifestations. Metabolic acidosis is characterized by a decrease in serum pH (7.35) and
HCO3 levels (24 mEq/L) due to H+ gain or HCO3- loss. Acidosis typically produces a compensatory
-

increase in respiratory rate with a decrease in PaCO 2. The manifestations of metabolic acidosis fall
into three categories: 1 - signs and symptoms of the disorder causing the acidosis, 2 - changes in body
function related to recruitment of compensatory mechanisms, and 3 - alterations in cardiovascular,
neurologic, and musculoskeletal function resulting from the decreased pH (Tab.3.)
The signs and symptoms of metabolic acidosis usually begin to appear when the serum HCO 3-
concentration falls to 20 mEq/L or less. A fall in pH to less than 7.0 to 7.10 can reduce cardiac
contractility and predispose to potentially fatal cardiac dyrhythmias. Metabolic acidosis is seldom a
primary disorder; it usually develops during the course of another disease. The manifestations of
metabolic acidosis frequently are superimposed on the symptoms of the contributing health problem.
With diabetic ketoacidosis, which is a common cause of metabolic acidosis, there is an increase in
blood and urine glucose and a characteristic smell of ketones to the breath. In metabolic acidosis that
accompanies chronic kidney disease, blood urea nitrogen levels are elevated and other tests of renal
function yield abnormal results. Manifestations related to respiratory and renal compensatory
mechanisms usually occur early in the course of metabolic acidosis. In situations of acute metabolic
acidosis, the respiratory system compensates for a decrease in pH by increasing ventilation to reduce
PCO2; this is accomplished through deep and rapid respirations (Fig.10). In diabetic ketoacidosis, this
breathing pattern is referred to as Kussmaul breathing. For descriptive purposes, it can be said that
Kussmaul breathing resembles the hyperpnea of exercise — the person breathes as though he or she
had been running. There may be complaints of difficulty breathing or dyspnea with exertion; with
severe acidosis, dyspnea may be present even at rest. Respiratory compensation for acute acidosis
tends to be somewhat greater than for chronic acidosis. When kidney function is normal, H+ excretion
increases promptly in response to acidosis, and the urine becomes more acid. Changes in pH have a
direct effect on body function that can produce signs and symptoms common to most types of
metabolic acidosis, regardless of cause. A person with metabolic acidosis often complains of
weakness, fatigue, general malaise, and a dull headache. They also may have anorexia, nausea,
vomiting, and abdominal pain. Tissue turgor is impaired, and the skin is dry when fluid deficit
accompanies acidosis. In persons with undiagnosed diabetes mellitus, the nausea, vomiting, and
abdominal symptoms may be misinterpreted as being caused by gastrointestinal flu or other abdominal
disease, such as appendicitis. Acidosis depresses neuronal excitability and decreases binding of
calcium to plasma proteins so that more free calcium is available to decrease neural activity. As
acidosis progresses, the level of consciousness declines, and stupor and coma develop. The skin is
often warm and flushed because blood vessels in the skin become less responsive to sympathetic
nervous system stimulation and lose their tone. When the pH falls to 7.0 to 7.1, cardiac contractility
and cardiac output decrease, the heart becomes less responsive to catecholamines (i.e., epinephrine
and norepinephrine), and arrhythmias, including fatal ventricular arrhythmias, can develop. A decrease
in ventricular function may be particularly important in perpetuating shock-induced lactic acidosis,
and partial correction of the acidemia may be necessary before tissue perfusion can be restored.
Chronic acidemia, as in chronic kidney disease, can lead to a variety of musculoskeletal problems,
some of which result from the release of calcium and phosphate during bone buffering of excess H +
ions. Of particular importance is impaired growth in children. In infants and children, acidemia may be
associated with a variety of nonspecific symptoms such as anorexia, weight loss, muscle weakness,
and listlessness. Muscle weakness and listlessness may result from alterations in muscle metabolism.

Table 3. Manifestations of Metabolic Acidosis and Alkalosis

(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .
 Fig. 10. Metabolic acidosis. Causes and compensation.
(From Despopoulos, Color Atlas of Physiology, 2003)
METABOLIC ALKALOSIS
Metabolic alkalosis is a systemic disorder caused by an increase in serum pH due to a primary
excess in HCO3-. It is reported to be the second most common acid-base disorder in hospitalized
adults, accounting for about 32% of all acid-base disorders. Most of the body’s serum HCO 3- is
obtained from CO2 that is produced during metabolic processes or from reabsorption of filtered HCO 3-
and generation of new HCO3- by the kidney. Usually, HCO 3- production and renal reabsorption are
balanced in a manner that prevents alkalosis from occurring. The proximal tubule reabsorbs 99.9% of
the filtered HCO3-. When the serum levels of HCO 3- rise above the threshold for tubular reabsorption,
the excess is excreted in the urine. Many of the conditions that increase serum HCO 3- also raise the
level for HCO3- reabsorption, and thus an increase in HCO3- contributes not only to the generation of
metabolic alkalosis, but also to its maintenance. Metabolic alkalosis can be caused by factors that
generate a loss of fixed acids or a gain of bicarbonate and those that maintain the alkalosis by
interfering with excretion of the excess bicarbonate (Fig. 9). They include (1) a gain of base via the
oral or intravenous route, (2) loss of fixed acids, and (3) maintenance of the increased bicarbonate
levels by contraction of the ECF volume, hypokalemia, and hypochloremia.
Excess Base Loading. Because the normal kidney is extremely efficient at excreting
bicarbonate, excess base intake is rarely a cause of significant chronic metabolic alkalosis. Transient
acute alkalosis, on the other hand, is a rather common occurrence during or immediately following
excess oral ingestion of bicarbonate-containing antacids (e.g., Alka-Seltzer) or intravenous infusion of
NaHCO3 or base equivalent (e.g., acetate in hyperalimentation solutions, lactate in Ringer lactate, and
citrate in blood transfusions). A condition called the milk alkali syndrome is a condition in which the
chronic ingestion of milk and/or calcium carbonate antacids leads to hypercalcemia and metabolic
alkalosis. In this case, the antacids raise the serum HCO 3- concentration, while the hypercalcemia
prevents the urinary excretion of HCO3-. The most common cause at present is the administration of
calcium carbonate as a phosphate binder to persons with chronic kidney disease.
Loss of Fixed Acid. The loss of fixed acids occurs mainly through the loss of acid from the
stomach and through the loss of chloride in the urine. Vomiting and removal of gastric secretions
through the use of nasogastric suction are common causes of metabolic alkalosis in acutely ill or
hospitalized patients. Bulimia nervosa with self induced vomiting also is associated with metabolic
alkalosis. Gastric secretions contain high concentrations of HCl and lesser concentrations of potassium
chloride. As Cl- is taken from the blood and secreted into the stomach, it is replaced by HCO3-. Under
normal conditions, each 1 mEq of H+ that is secreted into the stomach generates 1 mEq of serum
HCO3-. Thus, the loss of gastric secretions through vomiting or gastric suction is a common cause of
metabolic alkalosis. The accompanying ECF volume depletion, hypochloremia, and hypokalemia
serve to maintain the metabolic alkalosis by increasing HCO3- reabsorption by the kidneys (Fig. 5).
The loop and thiazide diuretics are commonly associated with metabolic alkalosis, the severity of
which varies directly with the degree of diuresis. The volume contraction and loss of H+ in the urine
contribute to the problem. The latter is primarily due to the enhanced H+ secretion in the distal tubule
that results from an interplay between the diuretic-induced increase in Na+ delivery to the distal tubule
and collecting duct where an accelerated excretion of H + and K+ takes place and an increase in
aldosterone secretion resulting from the volume contraction. Although aldosterone blunts the loss of
Na+, it also accelerates the secretion of K+ and H+. The resulting loss of K+ also accelerates HCO3-
reabsorption.
 Fig. 11. Renal mechanisms for bicarbonate (HCO3-) reabsorption and maintenance of metabolic
alkalosis following depletion of extracellular fluid volume, chloride (Cl-), and potassium (K+) due to
vomiting. GFR, glomerular filtration rate (From C. Porth and G. Matfin; Pathophysiology. Concepts of altered
health states).

Metabolic alkalosis can also occur with abrupt correction of respiratory acidosis in persons
with chronic respiratory acidosis. Chronic respiratory acidosis is associated with a compensatory loss
of H+ and Cl- in the urine along with HCO 3- retention. When respiratory acidosis is corrected abruptly,
as with mechanical ventilation, metabolic alkalosis may develop due to a rapid drop in PCO2, while
serum HCO3- , which must be eliminated through the kidney, remains elevated.
Maintenance of metabolic alkalosis. Maintenance of metabolic alkalosis resides within the
kidney and its inability to rid the body of the excess HCO 3-. Many of the conditions that accompany
the development of metabolic alkalosis, such as contraction of the ECF volume, hypochloremia, and
hypokalemia, also increase reabsorption of HCO3- by the kidney, thereby contributing to its
maintenance. Depletion of the ECF causes a decline in the glomerular filtration rate with a subsequent
increase in Na+ and H2O reabsorption. With depletion of Cl- due to the loss of hydrochloric acid in
conditions such as vomiting and nasogastric suction, the available anion for reabsorption with Na + is
HCO3-. Hypokalemia, which generally accompanies metabolic alkalosis, also contributes to its
maintenance. This is due partly to the direct effect of alkalosis on potassium excretion by the kidney
and partly to a secondary hyperaldosteronism resulting from volume depletion. In hypokalemia, the
distal tubular reabsorption of K+ is accompanied by an increase in H+ secretion. The secondary
hyperaldosteronism, in turn, promotes extensive reabsorption of Na+ from the distal and collecting
tubules and at the same time stimulates the secretion of H + from cells in the collecting tubules.
Hypokalemia induced in this manner further worsens the metabolic alkalosis by increasing HCO 3-
reabsorption in the proximal tubule and H+ secretion in the distal tubule.
 Manifestations. Metabolic alkalosis is characterized by a serum pH above 7.45, serum HCO 3-
above 29 mEq/L (29 mmol/L), and base excess above 3.0 mEq/L (3 mmol/L). Persons with metabolic
alkalosis often are asymptomatic or have signs related to ECF volume depletion or hypokalemia. The
manifestations of metabolic alkalosis are summarized in Table 3. Neurologic signs and symptoms
(e.g., hyperexcitability) occur less frequently with metabolic alkalosis than with other acid-base
disorders because HCO3- enters the cerebrospinal fluid (CSF) more slowly than CO 2. When neurologic
manifestations do occur, as in acute and severe metabolic alkalosis, they include mental confusion,
hyperactive reflexes, tetany, and carpopedal spasm. Metabolic alkalosis also leads to a compensatory
hypoventilation with development of various degrees of hypoxemia and respiratory acidosis.
Significant morbidity occurs with severe metabolic alkalosis, including respiratory failure,
arrhythmias, seizures, and coma.

RESPIRATORY ACIDOSIS
Respiratory acidosis occurs in conditions that impair alveolar ventilation and cause an increase
in serum PaCO2, also known as hypercapnia, along with a decrease in pH (Fig. 8.). Respiratory
acidosis can occur as an acute or chronic disorder. Acute respiratory failure is associated with a rapid
rise in arterial PaCO2 with a minimal increase in serum HCO3- and large decrease in pH. Chronic
respiratory acidosis is characterized by a sustained increase in arterial PaCO 2, resulting in renal
adaptation with a more marked increase in serum HCO 3- and a lesser decrease in pH. Respiratory
acidosis occurs in acute or chronic conditions that impair effective alveolar ventilation and cause an
accumulation of PaCO2. Impaired ventilation can occur as the result of decreased respiratory drive,
lung disease, or disorders of the chest wall and respiratory muscle. Less commonly, it results from
excess CO2 production.
Acute disorders of ventilation. Acute respiratory acidosis can be caused by impaired function
of the respiratory center in the medulla (as in narcotic overdose), lung disease, chest injury, weakness
of the respiratory muscles, or airway obstruction. Almost all persons with acute respiratory acidosis
are hypoxemic if they are breathing room air. In many cases, signs of hypoxemia develop prior to
those of respiratory acidosis because CO2 diffuses across the alveolar capillary membrane 20 times
more rapidly than oxygen.
Chronic disorders of ventilation. Chronic respiratory acidosis is a relatively common
disturbance in persons with chronic obstructive lung disease. In these persons, the persistent elevation
of PCO2 stimulates renal H+ secretion and HCO3+ reabsorption. The effectiveness of these
compensatory mechanisms can often return the pH to near-normal values as long as oxygen levels are
maintained within a range that does not unduly suppress chemoreceptor control of respirations. An
acute episode of respiratory acidosis can develop in persons with chronic lung disease who receive
oxygen therapy at a flowrate that is sufficient to raise their PO 2 to a level that produces a decrease in
ventilation. In these persons, the medullary respiratory center has adapted to the elevated levels of CO 2
and no longer responds to increases in PaCO 2. Instead, a decrease in the PO 2 becomes the major
stimulus for respiration. If oxygen is administered at a flow rate that is sufficient to suppress this
stimulus, the rate and depth of respiration decrease, and the PaCO 2 increases. That being said, any
person who is in need of additional oxygen should have it administered, albeit at a flow rate that does
not depress the respiratory drive.
Increased carbon dioxide production. Carbon dioxide is a product of the body’s metabolic
processes, generating a substantial amount of acid that must be excreted by the lungs or kidney to
prevent acidosis. An increase in CO2 production can result from numerous processes, including
exercise, fever, sepsis, and burns. For example, CO2 production increases by approximately 13% for
each 1˚C rise in temperature above normal. Nutrition also affects the production of CO 2. A
carbohydrate-rich diet produces larger amounts of CO 2 than one containing reasonable amounts of
protein and fat. In healthy persons, the increase in CO 2 is usually matched by an increase in CO2
elimination by the lungs, whereas persons with respiratory diseases may be unable to eliminate the
excess CO2.
Manifestations. Respiratory acidosis is associated with a serum pH below 7.35 and an arterial
PaCO2 above 50 mm Hg. The signs and symptoms of respiratory acidosis (Table 4) depend on the
rapidity of onset and whether the condition is acute or chronic. Because respiratory acidosis often is
accompanied by hypoxemia, the manifestations of respiratory acidosis often are intermixed with those
of oxygen deficit. Carbon dioxide readily crosses the blood-brain barrier, exerting its effects by
changing the pH of brain fluids. Elevated levels of CO2 produce vasodilation of cerebral blood vessels,
causing headache, blurred vision, irritability, muscle twitching, and psychological disturbances. If the
condition is severe and prolonged, it can cause an increase in CSF pressure and papilledema. Impaired
consciousness, ranging from lethargy to coma, develops as the PaCO2 rises to extreme levels. Paralysis
of extremities may occur, and there may be respiratory depression. Less severe forms of acidosis often
are accompanied by warm and flushed skin, weakness, and tachycardia.
Treatment. The treatment of acute and chronic respiratory acidosis is directed toward
improving ventilation. In severe cases, mechanical ventilation may be necessary. The treatment of
respiratory acidosis due to respiratory failure is discussed in.

Table 4. Manifestations of Respiratory Acidosis and Alkalosis

(From C. Porth and G. Matfin; Pathophysiology. Concepts of altered health states) .
 Fig. 12. Respiratory acidosis. Causes and compensation.
(From Despopoulos, Color Atlas of Physiology, 2003)
RESPIRATORY ALKALOSIS
Respiratory alkalosis is a systemic acid-base disorder characterized by a primary decrease in
blood PaCO2, also referred to as hypocapnia, which produces an elevation in pH and a subsequent
decrease in HCO3-. Because respiratory alkalosis can occur suddenly, a compensatory decrease in
bicarbonate level may not occur before respiratory correction has taken place.
Respiratory alkalosis is caused by hyperventilation or a respiratory rate in excess of that
needed to maintain normal PaCO2 levels. It may occur as the result of central stimulation of the
medullary respiratory center or stimulation of peripheral (e.g., carotid chemoreceptor) pathways to the
medullary respiratory center. Mechanical ventilation may produce respiratory alkalosis if the rate and
tidal volume are set so that CO 2 elimination exceeds CO2 production. Carbon dioxide crosses the
alveolar capillary membrane 20 times more rapidly than oxygen. Therefore, the increased minute
ventilation may be necessary to maintain adequate oxygen levels while producing a concomitant
decrease in CO2 levels. In some cases, respiratory alkalosis may be induced through mechanical
ventilation as a means of controlling disorders such as severe intracranial hypertension. Central
stimulation of the medullary respiratory center occurs with anxiety, pain, pregnancy, febrile states,
sepsis, encephalitis, and salicylate toxicity. Respiratory alkalosis has long been recognized as a
common acidbase disorder in critically ill patients, and is a consistent finding in both septic shock and
the systemic inflammatory response syndrome. Progesterone increases ventilation in women; during
the progesterone phase of the menstrual cycle, normal women increase their PaCO 2 values by 2 to 4
mm Hg and their pH by 0.01 to 02. Women also develop substantial hypocapnia during pregnancy,
most notably during the last trimester with PaCO2 values of 29 to 32 mm Hg. One of the most
common causes of respiratory alkalosis is hyperventilation syndrome, which is characterized by
recurring episodes of overbreathing often associated with anxiety. Persons experiencing panic attacks
frequently present in the emergency room with manifestations of acute respiratory alkalosis.
Hypoxemia exerts its effect on pH through the peripheral chemoreceptors in the carotid bodies.
Stimulation of peripheral chemoreceptors occurs in conditions that cause hypoxemia with relatively
unimpaired CO2 transport such as exposure to high altitudes.
Manifestations. Respiratory alkalosis manifests with a decrease in PaCO 2 and a deficit in
H2CO3. In respiratory alkalosis, the pH is above 7.45, arterial PaCO 2 is below 35 mm Hg, and serum
HCO3- levels usually are below 24 mEq/L (24 mmol/L). The signs and symptoms of respiratory
alkalosis are associated with hyperexcitability of the nervous system and a decrease in cerebral blood
flow (Table 4). Alkalosis increases protein binding of extracellular calcium. This reduces ionized
calcium levels, causing an increase in neuromuscular excitability. A decrease in the CO2 content of the
blood causes constriction of cerebral blood vessels. Because CO 2 crosses the blood-brain barrier rather
quickly, the manifestations of acute respiratory alkalosis are usually of sudden onset. The person often
experiences light-headedness, dizziness, tingling, and numbness of the fingers and toes. These
manifestations may be accompanied by sweating, palpitations, panic, air hunger, and dyspnea.
Chvostek and Trousseau signs may be positive, and tetany and convulsions may occur. Because CO 2
provides the stimulus for short-term regulation of respiration, short periods of apnea may occur in
persons with acute episodes of hyperventilation.

BIBLIOGRAPHY

1.CAROL MATTSON PORTH. Pathophysiology. Concepts of Altered Health States; 9th edition,
2014; pag 1062-1079

2. STEFAN SILBERNAGL and FLORIAN LANG. Color Atlas of Pathophysiology. 3rd edition,
2016, pag. 94-99