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The most common example of a dilutional acidosis is large resuscitation with normal saline, which

causes a hyperchloremic acidosis. Clinically significant metabolic acidosis in surgical patients is most

commonly related to net loss of bicarbonate. One means of classification would be renal acidosis versus

extrarenal acidosis. Renal acidosis is not as readily compensated because by definition the kidney’s

ability to regulate acid/base is compromised. Extrarenal acidosis can be further subdivided into

increased acid production (e.g., lactic acidosis in shock) or increase bicarbonate loss (e.g., fistula).

Increased Production of Organic Acids

Increased protein intake and tissue catabolism resulting in greater metabolism of sulfur-containing

amino acids can lead to generation of increased amounts of sulfuric acid. With normal kidney function,

any decline in serum bicarbonate concentration stimulates renal acid excretion, which can compensate

almost completely for the increase in acid production.

Nonrenal Loss of Bicarbonate

Diarrhea, intestinal or pancreatic fistulas, and burns can cause metabolic acidosis secondary to loss of

bicarbonate. Urinary diversion with segments of GI tract (ureterosigmoidostomy and ureteroileostomy)

can result in loss of bicarbonate with reabsorption of NH4Cl from the urine. The potential for fistulas to

result in metabolic acidosis depends on the concentration of bicarbonate in the fluid and the rate of

external drainage. For instance, metabolic acidosis is less common with biliary fistulas than pancreatic

fistulas. Biliary fistulas typically have only modest volumes with a bicarbonate concentration of

approximately 50 to 60 mEq/L, whereas pancreatic fistulas can have profuse output with a

concentration of 150 mEq/L.

Ketoacidosis

Normally, free fatty acids generated from breakdown of triglycerides in adipose tissue are either used as

an energy source by tissues such as muscle or carried to the liver, where they are reesterified to

triglycerides. Ketoacids are produced by mitochondrial metabolism of free fatty acids to acetyl CoA,

with subsequent formation of acetoacetate and β-hydroxybutyrate (redox forms of the same compound).

Under normal conditions, a small amount of ketoacid is produced. During prolonged starvation,

production of ketoacid increases to modest levels, providing an important source of energy to

nonhepatic tissues, particularly the brain. In DKA, the ketoacid production is excessive because of

insulin deficiency, which drives ketoacid production by increasing free fatty acid release from adipose

tissue, increasing transport of free fatty acids into hepatic mitochondria, promoting conversion of acetyl

CoA to ketoacids, and impairing extrahepatic use of ketoacids. Insulin deficiency also contributes to

hyperglycemia by decreasing the metabolism of glucose by extrahepatic tissues and increasing hepatic

production of glucose. The resulting osmotic glucose diuresis causes increased renal excretion of sodium

and water. Additional losses of sodium and potassium occur as a result of renal excretion of the excess

ketoacid anions. Potassium excretion is further enhanced by hyperaldosteronism due to increased

delivery of sodium to the distal tubule that occurs in association with the osmotic diuresis. Despite total

body potassium depletion, serum potassium concentration is often increased in DKA secondary to

metabolic acidosis, renal insufficiency, insulin deficiency, and hyperosmolality. These pathophysiologic

changes result in the typical clinical presentation, which includes dehydration, polyuria, polydipsia,

hyperglycemia, hyperventilation, and metabolic acidosis with an increased anion gap.

Lactic Acidosis

Lactic acidosis can be characterized as type A (caused by tissue hypoxia) or type B (other causes). The

generation of lactic acid is the final step of anaerobic glycolysis. Lactic acid is normally produced by

muscle, blood elements, intestine, and skin and is used by the liver and kidney. Normal serum lactate

concentration is below 2 mEq/L. Lactic acidosis secondary to hypoxia is usually due to increased

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production of lactate as well as decreased use, and exists when serum lactate concentration is greater

than 6 mEq/L.

The most common cause of type B lactic acidosis is ethanol intoxication. Lactic acidosis is caused by

increased generation of NADH by the metabolism of alcohol, which interferes with hepatic

gluconeogenesis and, therefore, lactate use.

In lactic acidosis, the L-isomer is usually elevated because of the specificity of mammalian lactate

dehydrogenase. Various bacteria found in colonic flora are capable of generating large amounts of Dlactic acid. D-lactic acidosis has been reported in humans only in the presence of short-gut syndrome

because the small bowel normally absorbs the dietary substrate for bacterial D-lactic acid production. In

addition, the colon must be selectively colonized by bacteria that possess D-lactate dehydrogenase.

Typically, the patient has short-gut syndrome, and the acidosis is preceded by food ingestion and is

accompanied by characteristic neurologic findings, including mental confusion, slurred speech,

staggering gait, and nystagmus. These neurologic manifestations are secondary to bacterial neurotoxins.

The acidosis is accompanied by an increased anion gap, but L-lactate and ketone levels are normal.

Treatment includes oral antibiotics, recolonization of the colon with non–D-lactate dehydrogenase–

forming bacteria, and a low-carbohydrate diet.

Renal Acidosis

The most common renal-associated acidosis in surgical patients is that of acute or chronic renal failure.

One of the kidney’s many important functions is to excrete acid. When GFR decreases so does the ability

to excrete acid, thus causing a metabolic acidosis.

The impaired ability of the kidney to excrete acid may be secondary to a decrease in the number of

functioning nephrons and is termed RTA. Type I (distal) RTA is most commonly caused by autoimmune

diseases (e.g., Sjogren disease or rheumatoid arthritis) and hypercalciuria in adults. Distal RTA leads to

impaired distal acidification.

Type II (proximal) RTA is caused by a reduction in proximal bicarbonate reabsorption – the most

common cause in adults being monoclonal gammopathies or medications such as carbonic anhydrase

inhibitors.

Clinical Features of Acute Metabolic Acidosis

The major cardiovascular effects of acute metabolic acidosis are peripheral arteriolar dilatation,

decreased cardiac contractility, and central venous constriction. These can lead to cardiovascular

collapse and pulmonary edema. Catecholamine secretion is stimulated by metabolic acidosis, and in

mild cases (pH >7.1), heart rate may be increased. In more severe metabolic acidosis (pH <7.1), the

direct effects of acidosis override the catecholamine effects and result in bradycardia and decreased

contractility. These depressive effects are magnified by β-blockers. In addition to these cardiovascular

effects, metabolic acidosis can increase oxygen delivery by shifting the oxygen–hemoglobin dissociation

curve to the right. In more prolonged metabolic acidosis, this may be partially offset by decreased

production of 2,3-diphosphoglycerate in red blood cells because of a slower rate of glycolysis. Metabolic

acidosis can also cause gastric distention, abdominal pain, nausea, and vomiting.

Algorithm 11-3. Guidelines for the treatment of diabetic ketoacidosis.

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Renal Compensation

The kidney is extremely sensitive to changes in serum bicarbonate concentration and responds by

increasing net acid excretion primarily in the form of ammonia excretion. Maximal renal compensation

requires 2 to 4 days. In addition, the maximal amount of ammonia excreted during acidosis depends on

factors such as glutamine delivery, GFR, and the type of anion that accompanies the acid, because renal

acid secretion is stimulated to varying degrees by different anions. Although renal compensation is

effective in achieving normal net acid excretion with extrarenal causes of metabolic acidosis, variable

results are seen with renal acidosis, especially distal RTA.

Respiratory Compensation

A decrease in blood pH causes an immediate stimulus to hyperventilate. Although effective in promptly

raising blood pH, early ventilatory compensation is only partial. Full respiratory compensation can

occur in 12 to 24 hours. The magnitude of the decrease in PCO2

in response to a given degree of

metabolic acidosis can be used to determine whether the metabolic acidosis is complicated by coexisting

respiratory acidosis or respiratory alkalosis. There are multiple equations that can describe this

relationship; whichever is easiest remembered can be utilized:

Arterial PCO2 = Serum HCO3

- + 15

Arterial PCO2 = 1.5 × Serum HCO3

- + 8 ± 2 (Winter equation)

The PCO2 can fall no lower than 8 to 12 mm Hg in response to a severe metabolic acidosis and this

compensation can only be maintained for a limited period of time due to respiratory muscle fatigue.

Treatment of Acute Metabolic Acidosis

In surgical and trauma patients, metabolic acidosis is often the result of inadequate tissue perfusion and

consequent lactic acidosis. Volume resuscitation alone may be enough to correct this acidosis. Attempts

to correct acidosis with exogenous bicarbonate without addressing inadequate tissue perfusion will be

unsuccessful. Furthermore, exogenous administration of bicarbonate may cause a superimposed

respiratory alkalosis and a deleterious left shift of the oxygen–hemoglobin dissociation curve, by not

allowing reversal of 2,3-diphosphoglycerate depletion, hence resulting in tissue hypoxia.

Diabetic Ketoacidosis

Initial therapy must include four components: intravenous fluid, insulin, potassium, and the need for

bicarbonate. Intravenous fluid should be given in the form of normal saline. On average 4 to 5 L of fluid

are required within the first 24 hours. While doing this, serum sodium levels should be monitored. The

initial dose of insulin is typically 0.1 unit/kg intravenous or 0.3 unit/kg subcutaneously administered.

Insulin should be redosed every 1 hour intravenously or every 2 hours subcutaneously until serum

glucose reaches 200 mg/dL. In terms of potassium replacement, it is paramount to ensure adequate

renal function (i.e., urine output of at least 0.5 mL/kg/hr). Once adequate urine output is assured,

potassium repletion is dosed. If the serum potassium is >5.3 then no further potassium should be given,

whereas if serum potassium is 3.5 to 5.3, 20 mEq is added to each liter of fluid. If the serum potassium

is <3.5 then 20 mEq/hr of potassium can be administered until serum potassium is in the ideal 3.5 to

5.3 range. Determination for bicarbonate therapy is largely based on pH. If the pH is <7 then it is

reasonable to dilute sodium bicarbonate (100 mmol) in 400 mL water and infuse over 2 hours, then

rechecking the pH (Algorithm 11-3).51,52

Metabolic Alkalosis

Sustained metabolic alkalosis occurs only if extracellular bicarbonate concentration is increased and

renal excretion of excess bicarbonate is inhibited. Extracellular bicarbonate concentration increases can

occur through several mechanisms. In surgical patients, loss of HCl is a frequent cause of metabolic

alkalosis, most commonly due to vomiting or nasogastric drainage in the presence of gastric outlet

obstruction. External loss of gastric acid results in a net gain in bicarbonate (generated by equimolar

gastric secretion of HCl), which causes alkalosis. Although the kidney can excrete excess bicarbonate,

this must be accompanied by excretion of sodium. Renal excretion of sodium is limited in the presence

of the volume depletion that occurs with external losses of gastric secretion. As volume depletion

progresses, sodium is conserved in exchange for hydrogen, and urine will become acidic, even in the

presence of severe metabolic alkalosis. This phenomenon is referred to as paradoxical aciduria.

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Increased extracellular bicarbonate concentration can occur with administration of either bicarbonate

or precursors of bicarbonate, such as lactate, citrate, or calcium carbonate, or as a result of increased

renal production of bicarbonate. Conditions in which acid excretion exceeds endogenous acid production

and in which the renal threshold for bicarbonate reabsorption is increased can result in metabolic

alkalosis. Such conditions include moderate potassium depletion, excess mineralocorticoids, and high

PCO2

.

Hypokalemia and cellular exchange of potassium for hydrogen can also lead to metabolic alkalosis.

Hypokalemia results in enhanced proximal tubular bicarbonate reabsorption and distal tubular acid

excretion. When potassium leaves the cell, it is exchanged for either sodium or hydrogen to maintain

electrical neutrality. Loss of potassium from the body then results in a net gain in bicarbonate in the

ECF.

Maintenance of elevated extracellular bicarbonate concentration can occur by a number of

mechanisms. Volume contraction leads to decrease in renal blood flow and GFR thus reducing the

filtered load of bicarbonate. This, in addition to increased proximal tubular reabsorption of bicarbonate,

maintains high extracellular concentrations of bicarbonate. High PCO2 causes an increase in renal

threshold for bicarbonate secondary to decreased intracellular pH of the renal tubular cell. The net

result is increased bicarbonate reabsorption.

Diuretics can cause or exacerbate metabolic alkalosis by both causing rapid contraction of

intravascular volume and increasing renal excretion of acid. Chloride deficiency is another common

factor that maintains an alkalotic state. In some instances of metabolic alkalosis, urinary excretion of

chloride is markedly reduced. Reversal of metabolic alkalosis in these cases can be readily achieved by

administration of chloride-containing solutions. Metabolic alkalosis can be categorically divided into

chloride-responsive and chloride-resistant types.

Clinical Features

Clinical signs of metabolic alkalosis may not be prominent because the condition usually develops

slowly. If acute, CNS manifestations of confusion, obtundation, stupor, and coma may be present as well

as tetany or neuromuscular irritability.

Respiratory Compensation

Respiratory compensation for metabolic alkalosis should raise the PCO2 by 0.7 mm Hg for every 1

mEq/L elevation in serum HCO3

-. Typically the arterial PCO2 does not go above 55 mm Hg. Among the

four major acid–base disorders, this compensatory mechanism is the least effective.60

Treatment

Correction of the underlying cause is the mainstay of treatment in this disorder. In general, correction

of potassium depletion and volume depletion corrects the metabolic alkalosis. Renal excretion of

bicarbonate cannot occur in the face of persistent volume depletion. Volume depletion should be

corrected with chloride-containing solutions. In patients without intravascular volume deficits, renal

excretion of bicarbonate can be enhanced by administration of the diuretic, carbonic anhydrase inhibitor

acetazolamide. In extremely rare circumstances where renal excretion of bicarbonate cannot be

increased because of underlying renal insufficiency or if the metabolic alkalosis is severe, acid may be

administered to titrate in opposition the excess extracellular bicarbonate. Acids that can be used include

ammonium chloride, arginine hydrochloride, lysine hydrochloride, or dilute hydrochloric acid (0.1N).

Partial correction of the alkalosis is the initial goal and a specialist should be involved prior to

instituting this care. In the face of frank renal failure, dialysis may be necessary to remove excess

bicarbonate.

Respiratory Alkalosis

Respiratory alkalosis is defined as increased extracellular pH secondary to decreased PCO2 with

hyperventilation. Hyperventilation and the ensuing fall in PCO2 may be secondary to hypoxia, reflex

stimulation from decreased pulmonary compliance, drugs, mechanical ventilation, or other causes.

Hypoxia stimulates ventilation through peripheral chemoreceptors in the carotid and aortic bodies.

Decrease in arterial partial pressure of oxygen (pO2

), rather than in oxygen content, is the main

stimulus. Acute drops in arterial pO2

result in sustained hyperventilation only when the PCO2 decreases

below 60 mm Hg. Although hyperventilation occurs with even slight degrees of hypoxia, the resulting

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