9
Fluid, Electrolyte, & Acid-Base Disorders
Tracey Dechert, MD
Fluid status, electrolyte homeostasis, and acid-base balance are clinical parameters of critical significance in surgical patients. Understanding normal physiology and pathophysiology related to these parameters is crucial.
FLUIDS & ELECTROLYTES
Surgical patients are at high risk for derangements of body water distribution, electrolyte homeostasis, and acid-base physiology. These disturbances may be secondary to trauma, preexisting medical conditions which alter normal physiology, or the nature of the surgery.
BODY WATER DISTRIBUTION & COMPOSITION
Total body mass is 45%-60% water. The percentage in any individual is influenced by age and lean body mass, therefore the percentage is higher in men compared to women, in children compared to adults, and in people of normal body habitus compared to the obese (Table 9–1). Two-thirds of total body water (TBW), 30%-40% of body mass, is intracellular; one-third, 15%-20% of total body mass, is extracellular. The extracellular fluid is divided into two compartments, with 80% (12%-16% of total body mass) in the interstitial compartment, and 20% (3%-4%) in the intravascular compartment. One-fifth of intravascular fluid is proximal to the arterioles, the remaining four-fifths is distal to the arterioles.
Table 9–1. Approximate percentage water of total body mass.
The intracellular, interstitial, and intravascular compartments each hold fluid characterized by markedly different electrolyte profiles (Figure 9–1). The main intracellular cation is the potassium ion (K+), while the main extracellular cation is the sodium ion (Na+). Not only the electrolyte profile, but also the protein composition of the fluids differs: intracellular cations are electrically balanced mainly by the polyatomic ion phosphate (PO43−) and negatively charged proteins, while extracellular cations are balanced mainly by the chloride ion (Cl−). The intravascular fluid has a relatively higher concentration of protein and lower concentration of organic acids than the interstitial fluid. This higher concentration of protein, chiefly albumin, is the main cause of the high colloid osmotic pressure of serum, which in turn is the chief regulator of the fluid distribution between the two extracellular compartments. The relationship between colloid osmotic pressure and hydrostatic pressure governs the movement of water across the capillary membrane, and is modeled by the Starling equation.
Figure 9–1. Electrolyte composition of human body fluids. Note that the values are in mEq/L of water, not of body fluid. (From Leaf A, Newburgh LH: Significance of the Body Fluids in Clinical Medicine, 2nd ed. Thomas, 1955.)
The body’s volume status and electrolyte composition are determined largely by the kidneys. The kidneys maintain a constant volume and osmolality by modulating how much free water and Na+ is reabsorbed from the renal filtrate. Antidiuretic hormone (ADH), also known as arginine vasopressin, is the chief regulator of osmolality. The peptide hormone is released from the posterior pituitary in response to increased serum osmolality. ADH induces translocation of aquaporin channels to the collecting duct epithelium, increasing permeability to water and causing reabsorption of free water from the renal filtrate. Thus water is retained, and the urine concentrated. In the absence of ADH, the collecting duct is impermeable to water, leading to water loss and production of dilute urine. At high physiologic levels ADH has a direct vasoconstrictive effect on arterioles.
The main determinant of Na+ reabsorption is the Na+ load in the renal filtrate. Most filtered Na+ (60%-70%) is reabsorbed in the proximal tubule. A further 20%-30% of filtered Na+ is reabsorbed in the thick ascending limb of the loop of Henle; reabsorption here is determined by the Na+ load delivered to the loop and a variety of hormones. The remaining distal tubule reabsorbs 5%-10% of filtered Na+; again, the exact percentage is determined by the Na+ load and a variety of hormonal factors, particularly aldosterone. The collecting duct reabsorbs a small percentage of filtered Na+ under the influence of aldosterone and natriuretic hormone. Under normal circumstances the kidneys will adjust excreted water and Na+ to match a wide spectrum of dietary intake.
Although the movement of ions and proteins between the different fluid compartments is normally restricted, water itself is freely diffusible between them. Consequently the osmolality of the different fluid compartments is identical, normally approximately 290 mOsm/kg. Control of osmolality occurs through regulation of water intake through diet and excretion through urine and insensible loses.
VOLUME DISORDERS
Hypo- and hypervolemia commonly occur in surgical patients, both following elective surgery and in the setting of trauma and acute care surgery. Volume disturbances run the gamut from being clinically insignificant to being immediately life threatening. The underlying cause of any volume disorder must be sought and addressed while the volume disorder itself is managed.
Etiology: Hypovolemia is common in surgical patients. It is typically caused by loss of isotonic fluids in the setting of hemorrhage, gastrointestinal losses (eg, gastric suctioning, emesis, and diarrhea), sequestration of fluids in the gut lumen (eg, bowel obstruction, ileus, and enteric fistulas), burns, and excessive diuretic therapy. In resource poor settings sweat is often an additional important fluid loss, for example, in a non–air-conditioned operating room. In all of these cases, loss of isotonic fluid results in loss of Na+ and water without significantly affecting the osmolality of the extracellular fluid compartment, thus there is very little shift of water into or out of the intracellular compartment. Hypovolemia stimulates aldosterone secretion from the zona glomerulosa of the adrenal cortex, leading to increased reabsorption of Na+ and water from the renal filtrate and excretion of low volumes (oliguria) of hypertonic urine with a low Na+ concentration.
Fractional excretion of Na+ (FENa) is a useful tool for differentiating causes of oliguria:
where U: urine, P: plasma, Na: sodium, Cr: creatinine.
FENa ≤1% usually indicates prerenal azotemia. However, FENa ≤1% may be found in patients with oliguria secondary to hepatorenal syndrome, as the liver does not effectively metabolize aldosterone. In patients already receiving diuretic therapy, fractional excretion of urea nitrogen (FEUN) is more helpful than FENa. FEUN is calculated analogously; FEUN ≤35% indicates prerenal azotemia.
Presentation: Hypovolemia is suggested by a patient’s history, physical examination, and laboratory data. Diagnosis by physical examination alone in the immediate postoperative setting is difficult, especially when volume loss is mild to moderate, and especially in very old and very young patients. One review found that longitudinal furrows on a patient’s tongue and dry oral and nasal mucous membranes are 85% sensitive for hypovolemia; increased capillary refill time, unclear speech, upper or lower extremity weakness, a dry axilla, and postural hypotension were all relatively specific indicators of hypovolemia. The same review found that a postural (supine to standing) increase in heart rate of at least 30 beats per minute or severe postural dizziness which prevented the patient from standing had 6%-48% sensitivity for mild to moderate hypovolemia but 91%-100% sensitivity for severe hypovolemia. Laboratory evidence of hypovolemia includes elevated blood urea nitrogen (BUN): creatinine (Cr) ratio, as hypovolemia decreases renal perfusion, causing prerenal azotemia characterized by a disproportionate rise in BUN compared to Cr. However, an elevated BUN: Cr ratio may also be associated with renal failure and with gastrointestinal bleeding, independent of volume status. No single highly sensitive test to diagnose hypovolemia exists, thus the diagnosis must be made by examining all available data with a high index of suspicion.
Treatment: Hypovolemia is corrected with intravenous administration of an isotonic fluid. Coexistent electrolyte abnormalities should be addressed simultaneously. Care must be taken in patients in renal or heart failure not to exacerbate these conditions. If hypovolemia is allowed to worsen unimpeded it will eventually lead to circulatory collapse and shock, which is covered elsewhere.
Etiology: Hypervolemia is also common in surgical patients. It often occurs after treatment of shock with colloid and crystalloid fluids, with or without attendant renal failure. It also occurs in the postoperative period as ADH is secreted in response to nonphysiologic stimuli, disrupting its role in regulation of osmolality. High physiologic levels of ADH have a vasoconstrictive effect, leading to a decreased filtered Na+ load and thus greater Na+ and water retention. This secretion of ADH typically ceases 2-3 days after the surgical insult, after which ADH levels return to an appropriate level and patients experience a so-called “autodiuresis.” Heart failure, liver disease, renal disease, and malnutrition all exacerbate hypervolemia in the surgical patient. Preexisting heart failure decreases the range across which a patient will adequately compensate for increased intravascular volume. Liver disease decreases metabolism of circulating ADH and aldosterone, increasing the homeostatic set point for intravascular volume and thus decreasing the physiologic reserve remaining to respond to surgical insults. Renal disease disrupts all aspects of volume regulation. Syndrome of inappropriate ADH hypersecretion (SIADH) causes hypervolemia secondary to a sustained ADH release independent of the normal physiologic triggers. SIADH typically occurs in the setting of traumatic brain injury, brain tumors and abscesses, pneumonia and lung abscesses, as a paraneoplastic syndrome associated with small cell lung cancer and other neoplasias, and with a variety of drugs including morphine and the chemotherapeutic agents cyclophosphamide and vincristine.
Presentation: Like hypovolemia, hypervolemia is often suggested by the patient’s history and physical examination. Signs include hypertension, decreased arterial oxygen saturation and basilar crackles, jugular venous distention, dependent soft tissue edema, gallop rhythms on cardiac auscultation, and rapid weight gain. Examination of recorded fluid administration may assist in the diagnosis. Eventually a hypervolemic patient may show signs of pulmonary edema, easily diagnosed on chest x-ray, or even congestive heart failure (CHF).
Treatment: If the hypervolemic patient develops CHF or pulmonary edema, treatment with diuretics, or in extreme cases hemodialysis, may be required. Mechanical ventilation may be lifesaving if pulmonary edema and/or CHF have progressed to the point of respiratory failure.
ELECTROLYTE DISORDERS
Electrolyte derangements may occur independently of each other, but are often closely linked. Like volume disorders, disturbances of electrolyte homeostasis run the gamut from mild and inconsequential to severe and immediately life threatening.
The underlying cause of any electrolyte disorder must be sought while the electrolyte disorder itself is managed. Special care must always be taken when repleting electrolytes in patients with renal insufficiency. These patients require slower repletion and more frequent monitoring of electrolyte levels.
Hyponatremia
Etiology: Hyponatremia is a sign of relative water gain; total body Na+ may be decreased, normal or even increased. Hyponatremia is common in surgical patients postoperatively, as ADH is secreted in response to pain, nausea and vomiting, opiate administration, and positive-pressure ventilation. Typically, this hyponatremia is mild and inconsequential; however, it may be exacerbated by rapid parenteral administration of hypotonic fluids. Hyponatremia may result from severe hyperglycemia, or any other condition in which an osmotically active solute draws water from the intracellular space to the extracellular space. In the setting of hyperglycemia, a corrected Na+ is calculated as:
The correction factor 0.016 accounts for the unit conversion from mg/dL to mmol/L. Some investigators believe a correction factor of 0.024 is more appropriate.
Other causes of hyponatremia include cerebral salt-wasting syndrome, liver disease, congestive heart failure, and SIADH.
Presentation: The signs of hyponatremia are caused by CNS dysfunction, as brain cells swell in a fixed-volume space (the Monro-Kellie hypothesis). Mental status changes, obtundation, coma, and seizures typically are not seen until serum Na+ is less than 120 mmol/L. Such hyponatremia is a medical emergency requiring immediate intervention.
Treatment: CNS signs and symptoms attributable to hyponatremia require administration of normal saline and free water restriction. In general, hypertonic saline should not be used to correct hyponatremia. Unless serum Na+ falls very rapidly, it should be corrected slowly, as too-rapid correction has the devastating complication of osmotic demyelination. No consensus exists on the appropriate rate of correction. One review recommended correction by no more than 8 mmol/L/d, starting with correction of 1-2 mmol/L/h in patients with severe manifestations. Sodium levels should not be corrected beyond what is needed to alleviate CNS disturbances. Correction of Na+ does not replace pharmacologic intervention in a seizing patient.
One formula used to calculate the expected change in Na+ from intravenous administration of 1 L of any fluid is:
Total body water is estimated as a fraction of body mass (Table 9–1). Hyponatremia causing CNS disturbances should prompt admission to an intensive care unit given the close monitoring needed in such patients, the need for rapid intervention, and the potentially devastating consequences of delays in management.
Hypernatremia
Etiology: Loss of free water alone occurs when patients do not have access to water (eg, preverbal, bed-bound or otherwise incapacitated patients), in diabetes insipidus, in the setting of high fevers, and in patients in whom enteral feeds do not contain adequate water. Hypernatremia typically occurs simultaneously with volume derangements, and total body Na+ may be increased, normal or even decreased. Induced hypernatremia is a useful treatment modality in patients with traumatic brain injury to reduce cerebral edema, decrease intracranial pressure, and increase cerebral perfusion pressure.
Presentation: As with hyponatremia, the signs and symptoms of hypernatremia are caused by CNS dysfunction: lethargy, fatigue, hyperactive deep tendon reflexes, seizure, and coma may occur. Signs and symptoms are rare with Na+ less than 158 mmol/L.
Treatment: Development of CNS symptoms requires parenteral administration of free water, typically as 5% dextrose in water. If the patient’s hypernatremia developed over a period of hours it may safely be corrected at a rate of 1 mmol/L/h. In patients whose hypernatremia developed more slowly, a rate of 0.5 mmol/L/h is safe. As derangements in Na+ are caused by derangements in TBW, the concept of a “water deficit” is a useful one in treating hypernatremia. The free water deficit is calculated as:
water deficit = (TBW × (1 − [140/Na+ in mmol/L])
This formula is accurate when calculating the water deficit in patients with pure water loss, but is inaccurate in patients with hypernatremia caused by loss of hypotonic fluid. Using the formula in the section on hyponatremia, one may calculate the estimated correction 1 L of any fluid will have on Na+. As with hyponatremia, hypernatremia with clinical manifestations warrants admission to an intensive care unit so that correction may be achieved safely and effectively.
Hypokalemia
Etiology: In the surgical setting, total body K+ is typically decreased by gastrointestinal losses, excessive diuretic administration, and prolonged malnutrition, particularly in alcoholic patients. Prolonged alkalosis (see below) that also results in hypokalemia (eg, due to gastric losses of hydrochloric acid and K+) results in a so-called “paradoxical aciduria” as the nephron conserves K+ at the expense of H+, which maintains the alkalosis instead of correcting it an attempt to prevent life-threatening hypokalemia (see below for details).
Presentation: The hallmark signs of hypokalemia are decreased muscle contractility eventually leading to diaphragmatic paralysis, EKG changes including a flattened or inverted T wave and a prominent U wave, and cardiac arrhythmias, which may present an immediate threat to life.
Treatment: When hypokalemia develops acutely it should be corrected with parenteral supplementation. Parenteral administration of K+ must be done carefully so as not to cause iatrogenic hyperkalemia. Hypomagnesemia may cause hypokalemia refractory to parenteral administration. In such cases hypomagnesemia should be corrected along with hypokalemia (see below). In cases of chronic hypokalemia in which neuromuscular and cardiac manifestations are absent, oral supplementation (either through dietary changes or oral potassium chloride administration) should suffice.
Hyperkalemia
Etiology: In the surgical setting, hyperkalemia is often caused by crush injuries, burns and other catabolism-inducing events, renal insufficiency, adrenal insufficiency, and excessive K+ administration. Acidosis may cause hyperkalemia as the intracellular space buffers acidemia by exchanging H+ from the extracellular space for K+ from within cells (see below).
Presentation: Hyperkalemia has few outward signs and symptoms until potentially lethal cardiac arrhythmias manifest. Initial EKG changes include flattened P waves and peaked T waves. Widening of the QRS complex is a later finding and demands immediate intervention, as it portends the imminent onset of ventricular fibrillation.
Treatment: A serum K+ of 6.5 mmol/L or greater is a medical emergency and must prompt immediate intervention. The patient must be placed on continuous EKG monitoring. Initial treatment should consist of intravenous administration of 50% dextrose in water, 10 units of regular insulin, and calcium gluconate, as well as inhaled β-adrenergic agonists like albuterol. Insulin, glucose, and β-agonists drive K+ from the extracellular space into the intracellular space, while calcium gluconate increases the excitability threshold of the myocardium, protecting against arrhythmias. If these measures are unsuccessful, hemodialysis may be required. Slowly developing hyperkalemia not severe enough to warrant intravenous interventions may be treated with oral sodium polystyrene sulfonate, which causes a slow enteral K+ wasting.
Hypomagnesemia
Etiology: Hypomagnesemia occurs in the setting of malnutrition (especially malnutrition associated with alcoholism), gastrointestinal losses (especially prolonged diarrheal loses), diuretic or aminoglycoside use, hyper- or hypocalcemia, and hypophosphatemia.
Presentation: In the surgical setting, hypomagnesemia most commonly presents as hypokalemia refractory to parenteral K+ administration. Hypomagnesemia may cause sedation, muscle paralysis, tetany, seizures, and coma.
Treatment: Parenteral administration of Mg2+ is generally preferred to oral supplementation, as orally-administered magnesium is a cathartic agent.
Hypermagnesemia
Etiology: Hypermagnesemia is rare in the surgical setting, but may develop in acute renal failure.
Presentation: At high concentrations, Mg2+ acts as a Ca2+ antagonist. Thus although hypermagnesemia may cause lethargy, weakness and diminished deep tendon reflexes, it most often presents as cardiac arrhythmias. Peaked T waves and widening of the QRS complex occur, which may progress to complete heart block, arrhythmias, and eventually asystole.
Treatment: If hypermagnesemia is mild and caused by supplementation, withdrawal of supplementation, and close monitoring should be sufficient treatment. If hypermagnesemia is significant and causing EKG changes, calcium gluconate should be administered intravenously so as to overwhelm the Ca2+-antagonizing effect of Mg2+ in neuromuscular function. Diuretic therapy may be required. In severe cases and in cases caused by renal failure, hemodialysis may be required.
Standard laboratory tests measure total serum Ca2+, including the fraction bound to albumin. Thus, a low Ca2+ value on a serum chemistry may reflect hypoalbuminemia rather than true hypocalcemia. Many formulas exist to correct Ca2+ in the setting of hypoalbuminemia. The most commonly used is:
Ca2+corrected = 0.8(4 − serum albumin in g/dL) + Ca2+measured
This and other such formulas are inaccurate in the setting of hemodialysis. In dialyzed patients, the uncorrected Ca2+ should be used to determine if the patient is hypo- or hypercalcemic. If doubt exists, an ionized Ca2+ measurement should be obtained.
Hypocalcemia
Etiology: Hypocalcemia in the surgical setting is often caused by hypothyroidism and hypoparathyroidism (either organic or iatrogenic after thyroid or parathyroid surgery), pancreatitis, renal insufficiency, crush injuries, severe soft tissue infections, and necrotizing infections like necrotizing fasciitis.
Presentation: Hypocalcemia manifests as neuromuscular dysfunction, causing hyperactive deep tendon reflexes, Chvostek sign, muscle cramps, abdominal pain, and in severe cases tetany and cardiac arrhythmias.
Treatment: In persistent hypocalcemia, whole blood pH must be determined, and any alkalosis corrected. Calcium supplementation, enterally if possible and parenterally if necessary, may be required. Chronic hypoparathyroidism and hypothyroidism require chronic vitamin D and Ca2+ supplementation, and may require aluminum hydroxide to decrease PO43− absorption from the gut.
Hypercalcemia
Etiology: Hypercalcemia in the surgical setting is often caused by primary or tertiary hyperparathyroidism, hyperthyroidism, bony cancer metastases, paraneoplastic syndromes in which parathyroid hormone-related peptide is elaborated, and as a complication of thiazide diuretic use.
Presentation: Signs and symptoms of acute hypercalcemia include anorexia, nausea and vomiting, polydipsia, polyuria, depression, confusion, memory loss, stupor, coma, psychosis, and cardiac arrhythmias. Dyspepsia, constipation, acute pancreatitis, nephrolithiasis, osteoporosis, osteomalacia, and osteitis fibrosa cystica are indicative of chronic hypercalcemia. Untreated longstanding hypercalcemia, especially in conjunction with untreated hyperphosphatemia and especially in patients with chronic renal failure, may lead to calciphylaxis and high morbidity and mortality.
Treatment: In a patient with healthy kidneys, administration of large volumes of normal saline over 1-3 days will often correct even a profound hypercalcemia. Treatment may be followed by targeting a urine output of 2-3 mL/kg/h and monitoring serum Ca2+ levels closely. Loop diuretics (eg, furosemide) inhibit Ca2+ reabsorption in the nephron, and will aid in calciuresis, but should not be used until the patient is clinically euvolemic. Calcitonin increases osteoblastic activity and inhibits osteoclastic activity, locking Ca2+ into the skeleton. In severe hypercalcemia or hypercalcemia secondary to renal failure, hemodialysis may be required. In patients whose hypercalcemia is caused by malignancy, bisphosphonates may provide a means of controlling Ca2+ levels in the medium and long term. In hypercalcemia caused by hyperparathyroidism, parathyroidectomy is potentially curative, but is reserved for the elective setting unless the patient is in hypercalcemic crisis which is refractory to optimal medical management.
Hypophosphatemia
Etiology: As with hypomagnesemia, chronic hypophosphatemia is typically found in malnourished patients, especially alcoholic patients. It may also occur in patients who consume large amounts of antacids, and following liver resection. An important and often overlooked cause of hypophosphatemia is refeeding syndrome. This syndrome occurs after a patient who has been without significant caloric intake for at least 5 days begins to eat again. Severe hypophosphatemia may occur as phosphofructokinase binds PO43− to glucose to begin glycolysis, and as PO43− is consumed in production of large amounts of ATP. The syndrome usually manifests within 4 days of starting refeeding.
Presentation: Hypophosphatemia results in muscular and neurologic dysfunction. Muscle weakness, diplopia, depressed cardiac output, respiratory depression due to diaphragmatic weakness, confusion, delirium, coma, and death may all develop. An uncommon presentation is with rhabdomyolysis. Hypophosphatemia may leave a patient ventilator-dependent as they are unable to replenish ATP stores for proper functioning of the muscles of respiration.
Treatment: Severe hypophosphatemia is a medical emergency, requiring parenteral administration of Na3PO4 or K3PO4, depending on the patient’s electrolyte profile. If hypophosphatemia is not severe it may be treated with oral supplementation, either with sodium phosphate/potassium phosphate or with high-phosphate foods like milk.
Hyperphosphatemia
Etiology: Hyperphosphatemia is unusual in the surgical setting, typically developing in the setting of severe renal disease or after severe trauma.
Presentation: Hyperphosphatemia is usually asymptomatic, but it may cause hypocalcemia as calcium phosphate precipitates and is deposited in tissues.
Treatment: Hyperphosphatemia is treated by diuresis, administration of phosphate-binders like aluminum hydroxide, or hemodialysis in the setting of renal failure.
ACID-BASE
The body’s handling of hydrogen ion (H+) is a particularly complex example of electrolyte management, as it involves not only dietary intake and renal clearance but also extracellular and intracellular buffer systems and respiratory as well as renal excretion.
NORMAL PHYSIOLOGY
An acid is a chemical that donates a H+ in solution, for example, HCl or H2CO3. A base is a chemical that accepts H+ in solution, for example, Cl− or HCO3−. The concentration of H+ in a solution determines the acidity of the solution. Acidity of a solution is measured by pH, which is the negative logarithm of H+ concentration expressed in mol/L. The strength of an acid is determined by its degree of dissociation into H+ and the corresponding base, as expressed in the Henderson-Hasselbalch (H-H) equation:
where K = dissociation constant, [A−] = concentration of acid, [HA] = concentration of base. Stronger acids have a higher K than weaker acids.
The main buffer system in human blood is a carbonic acid/bicarbonate (H2CO3/HCO3−) system. Using the H-H equation, the pH of this buffer system is calculated as:
H2CO3 in the blood exists mostly as CO2 (the so-called “volatile acid”); conversion of one to the other is catalyzed by the enzyme carbonic anhydrase. The dissociation constant of CO2 is 0.03. Making these substitutions into the equation, we have:
where Pco2 is the partial pressure of CO2. The pK for this buffer system is 6.1. In arterial blood, HCO3− normally ranges from 21 to 37 mmol/L, while Pco2 ranges from 36 to 44 mm Hg. Thus, arterial pH normally ranges from 7.36 to 7.44. Venous blood is easier to sample than arterial blood (Table 9–2). Venous blood gas sampling varies significantly between institutions, and between central, mixed, and different peripheral sites of sampling, and thus must be interpreted with caution.
Table 9–2. Estimated arterial to venous blood gas conversions.
|
pHa = pHv × 1.005 |
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Paco2 = Pvco2 × 0.8 |
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HCO3−a = HCO3−v × 0.90 |
a, arterial; p, partial pressure; v, venous.
Acid-base homeostasis is maintained by pulmonary excretion of CO2 and renal excretion of nonvolatile acids, which is discussed in further sections.
a, arterial; p, partial pressure; v, venous.
ACID-BASE DISORDERS
The fundamental acid-base disorders are:
There are four primary or simple (as opposed to mixed) acid-base disorders:
Acid-base disorders are classified as simple or mixed. In a simple acid-base disorder, only one primary acid-base disorder is present, and the compensatory response is appropriate. In a mixed acid-base disorder, more than one primary acid-base disorder is present. Mixed acid-base disorders are suspected from a patient’s history, from a lesser or greater than expected compensatory response, and from analysis of the serum electrolytes and anion gap (AG) (see below).
The use of a systematic approach to identifying and diagnosing acid-base disorders is essential. One must first determine alkalemia or academia based on pH. One must then determine whether a metabolic derangement with respiratory compensation or a respiratory derangement with metabolic compensation exists, based on the HCO3− and Pco2 values (Table 9–3).
Table 9–3. Changes in HCO3− and pCO2 in primary acid-base disorders.
Whether the disturbance is primarily respiratory or metabolic, some degree of compensatory change occurs in an attempt to maintain normal pH. Changes in Pco2 (respiratory disorders) are compensated for by changes in HCO3− (metabolic/renal compensation), and vice versa.
Acute respiratory disorders may develop in matter of moments. Such circumstances may not allow sufficient time for renal compensation, resulting in severe pH changes without significant compensatory changes. By contrast, chronic respiratory disturbances allow the full range of renal compensatory mechanisms to function. In these circumstances, pH may remain normal or nearly normal despite wide variations in Pco2. By contrast, respiratory compensation for metabolic disorders occurs quickly. Thus there is little difference in respiratory compensation for acute and chronic metabolic disorders.
Metabolic Acidosis
Metabolic acidosis is caused by increased production of H+ or by excessive loss of HCO3−. In the surgical setting, metabolic acidosis is commonly encountered in trauma, critically ill, and postoperative patients, and especially in patients in shock.
The serum AG is vital to determining the cause of any metabolic acidosis. AG may help differentiate between metabolic acidosis caused by accumulation of acid and that caused by loss of HCO3−.
AG represents the difference between the primary measured serum cation, Na+, and the primary measured serum anions, Cl− and HCO3−:
The AG is normally less than 12; however, the highest normal value varies by institution.
Increased acid production causes an increased AG, as unmeasured anions electrically neutralize Na+. Thus metabolic acidosis caused by increased H+ production is associated with a high AG. The most common causes of an AG metabolic acidosis include methanol ingestion, uremia/renal failure, diabetic ketoacidosis, polypropylene glycol ingestion, isoniazid ingestion, lactic acidosis, ethylene glycol ingestion, and salicylate poisoning. In the surgical setting lactic acidosis is by far the most common cause, seen in hypoperfused states like shock and sepsis.
A non-AG metabolic acidosis is caused by excessive HCO3 loss. The nephron maintains electrical neutrality by reabsorbing Cl− as HCO3− is lost, hence the normal AG. Non-AG metabolic acidosis in the surgical setting typically results from diarrhea or high small bowel output, for example, from an ileostomy. Non-AG acidosis also occurs in renal tubular acidosis, as the nephron fails to reabsorb HCO3−. Iatrogenic hyperchloremia, especially from administration of large amounts of normal saline to trauma and postoperative patients, may induce a non-AG metabolic acidosis.
The AG may be influenced by phenomena unrelated to acid-base balance, which must be kept in mind. Hypoalbuminemia may lower AG, as Cl− and HCO3− increase to electrically balance Na+ which was previously balanced by albumin. Similarly, hyper- or hypostates of positively charged ions like calcium, magnesium, and potassium may affect the AG.
Treatment of metabolic acidosis involves identifying the underlying cause of the acidosis and correcting it. Often, this is sufficient. If this is not sufficient, correction may require administration of exogenous alkali in the form of NaHCO3− to correct the derangement in pH. The degree of restoration is estimated by subtracting the plasma HCO3− from the normal value (24 mmol/L at our institution) and multiplying the resulting number by half TBW. This is a useful empiric formula, as in practice it is unwise (and unnecessary) to administer enough NaHCO3− to completely correct pH. Doing so will likely cause fluid overload from the large Na+ load delivered, and will likely overcorrect the acidosis. In patients with a chronic metabolic acidosis, often seen in chronic renal failure, alkali may be administered chronically as oral NaHCO3−. Efforts to minimize the magnitude of HCO3− loss in these patients must be undertaken as well.
The body’s response to metabolic acidosis is respiratory hyperventilation, “blowing off” H2CO3 as CO2 and correcting the acidosis. This response is rapid, beginning within 30 minutes of the onset of acidosis and reaching full compensation within 24 hours. The adequacy of the respiratory response to metabolic acidosis is evaluated using Winter’s formula:
If compensation is inadequate or excessive—that is, if Pco2 is not within the range predicted by Winter’s formula—one must evaluate for a mixed acid-base disorder (see below).
Metabolic Alkalosis
Metabolic alkalosis is often encountered in surgical patients. The pathogenesis is complex, but often involves:
All three are commonly encountered with vomiting or gastric suctioning, diuretic use, and renal failure.
HCl is secreted by chief cells in the gastric mucosa; simultaneously, HCO3− is absorbed in the blood. NaHCO3 is then secreted by the pancreas into the lumen of the duodenum, neutralizing the gastric acid, after which the neutralized acid and base are reabsorbed by the small intestine. Thus, under normal circumstances there is no net alteration of acid-base balance in the function of the gastrointestinal tract. However, when H+ is lost from the gastric lumen, for example, through emesis, gastric suctioning or gastric drainage—the result is loss of H+ from the gastric lumen and a corresponding gain of HCO3− in the blood, leading to metabolic alkalosis.
Normally, the kidneys excrete excess HCO3−; however, if volume depletion accompanies HCO3− excess, the kidneys attempt to maintain normovolemia by increasing tubular reabsorption of Na+, which is reabsorbed in an electrically neutral fashion by increasing reabsorption of Cl− and HCO3−. This impairs HCO3− excretion, perpetuating the metabolic alkalosis.
Severe K+ depletion further exacerbates metabolic alkalosis. To preserve K+, Na+ is exchanged for H+ in the kidney, through the Na+-K+ and Na+-H+ ATPases in the distal renal tubule. This explains why severe metabolic alkalosis with hypokalemia results in paradoxical aciduria. In such cases, urine Na+, K+, and Cl− concentrations are low, and the urine is acidic. In simple volume depletion, urine Cl−alone is low and the urine is alkaline. Severe metabolic alkalosis may lead to tetany and seizures, as seen in hypokalemia and hypocalcemia.
Treatment of metabolic alkalosis includes fluid administration, usually normal saline. With adequate fluid repletion, tubular reabsorption of Na+ is diminished, and the kidneys will excrete excess HCO3−. K+ must be repleted, both to allow for correction of the alkalosis and to prevent life-threatening hypokalemia. Repletion of volume with normal saline and of potassium with KCl also provides the nephron with needed Cl−, allowing for reabsorption of K+ and Na+ with Cl− instead of HCO3−. Acetazolamide, a carbonic anhydrase inhibitor diuretic, may also be used to treat metabolic alkalosis as long as the patient is euvolemic. Administration of exogenous acid in the form of HCl may be employed in the case of profound alkalosis.
Adequate respiratory compensation for metabolic alkalosis should raise Pco2 by 0.7 mm Hg for every 1 mmol/L elevation in HCO3−. Generally, respiratory compensation will not raise Pco2 beyond 55 mm Hg. Thus a Pco2 greater than 60 mm Hg in the setting of metabolic alkalosis suggests a mixed metabolic alkalosis and respiratory acidosis.
Respiratory Acidosis
Acute respiratory acidosis occurs when ventilation suddenly becomes inadequate. CO2 accumulates in the blood, and as carbonic anhydrase coverts it to H2CO3, acidosis develops.
Acute respiratory acidosis is most common in conditions where gas exchange is physically impaired, resulting in decreased ventilation. These conditions typically involve decreased oxygenation as well. They include respiratory arrest, acute airway obstruction, pulmonary edema, pneumonia, saddle pulmonary embolus, aspiration of intraoral contents, and acute respiratory distress syndrome. Hypoventilation may occur in patients postoperatively who are oversedated (eg, from narcotics, benzodiazepines, or as they recover from general anesthesia). Pain, especially from large abdominal incisions or from rib fractures, leads to respiratory splinting and hypoventilation. Excess ethanol ingestion decreases respiratory drive, thereby impairing ventilation. Head trauma, either by direct damage to central nervous system respiratory centers or by global brain damage and brainstem herniation, may impair ventilation.
Patients with obesity hypoventilation syndrome and obstructive sleep apnea may develop a periodically recurring acute respiratory acidosis, leading eventually to some renal compensation. True chronic respiratory acidosis arises from chronic respiratory failure in which impaired ventilation leads to persistently elevated Pco2, for example, as seen in chronic obstructive pulmonary disease. Chronic respiratory acidosis is usually well tolerated with adequate renal compensation, thus pH may be normal or near normal.
Treatment of respiratory acidosis involves restoration of adequate ventilation by treating the underlying cause. Aggressive chest physical therapy and pulmonary toilet should be instituted on all postsurgical patients. Patients with pulmonary edema should receive appropriate diuretic therapy, and patients with pneumonia should receive appropriate antibiosis. Naloxone or flumazenil should be used as needed in the setting of narcotic or benzodiazepine overdose, respectively. If necessary, endotracheal intubation and mechanical ventilation should be employed in order to correct pCO2.
Acute respiratory acidosis should be corrected rapidly. However, too rapid correction of chronic respiratory acidosis risks causing posthypercapnic metabolic alkalosis syndrome, characterized by muscle spasms and by potentially lethal cardiac arrhythmias.
Over 80% of increased acid produced in respiratory acidosis is buffered by the body’s tissues and intracellular hemoglobin. The remaining minority is buffered by HCO3− in the blood, which the kidney reclaims and reabsorbs. Thus, metabolic (renal) compensation for respiratory disorders is a much slower process than respiratory compensation for metabolic disorders. Furthermore, in acute respiratory acidosis renal mechanisms may not have had time to function at all, and HCO3− may be within normal limits. Adequate renal compensation for respiratory acidosis involves an increase in HCO3− of 1 mmol/L for every 10 mm Hg increase in Pco2.
Respiratory Alkalosis
Hyperventilation decreases Pco2 (hypocapnia), leading to a respiratory alkalosis. In the surgical setting, anxiety, agitation, and pain are common causes of respiratory alkalosis. Hyperventilation and respiratory alkalosis may be an early sign of sepsis and of moderate pulmonary embolism. Chronic respiratory alkalosis occurs in chronic pulmonary and liver disease.
Acute respiratory alkalosis is treated by addressing the underlying cause. Patients may require pain control, sedation/anxiolytics, and even paralyzation and mechanical ventilation if necessary. Well-compensated chronic respiratory alkalosis does not require treatment. In these cases, rapid correction of pCO2 leads to so-called posthypocapnic hyperchloremic metabolic acidosis, which is often severe.
The renal response to respiratory alkalosis is decreased reabsorption of filtered HCO3− and increased urinary HCO3− excretion. HCO3− decreases as Cl− increases, since Na+ is reabsorbed with Cl− instead of with HCO3−. This same pattern is seen in hyperchloremic metabolic acidosis; the two are distinguished only by pH measurements.
Adequate renal compensation for respiratory alkalosis involves a decrease in HCO3− of 2 mmol/L for every 10 mm Hg decrease in Pco2.
Mixed Acid-Base Disorders
Many common pathophysiologic processes cause mixed acid-base disorders. In these situations, pH may be normal or near normal, but compensatory changes are either inadequate or exaggerated. One way of determining the presence of a simple versus mixed disorder is to plot the patient’s acid-base disorder on a nomogram (Figure 9–2). If the set of data falls outside one of the confidence bands, then by definition the patient has a mixed disorder. If the acid-base data falls within one of the confidence bands, the patient more likely has a simple acid-base disorder.
Figure 9–2. Acid-base nomogram for use in evaluation of clinical acid-base disorders. Hydrogen ion concentration (top) or blood pH (bottom) is plotted against plasma HCO3− concentration; curved lines are isopleths of CO2 tension (Paco2, mm Hg). Knowing any two of these variables permits estimation of the third. The circle in the center represents the range of normal values; the shaded bands represent the 95% confidence limits of four common acid-base disturbances: I, acute respiratory acidosis; II, acute respiratory alkalosis; III, chronic respiratory acidosis; IV, sustained metabolic acidosis. Points lying outside these shaded areas are mixed disturbances and indicate two primary acid-base disorders.
As with simple acid-base disorders, a systematic approach to mixed acid-base disorders is essential. First, determine the primary acid-base disorder. Next, determine whether or not adequate compensation has occurred, using the equations and rules given above (Table 9–4). If compensation is “inadequate,” meaning too little or too much, the patient has a mixed acid-base disorder.
Table 9−4. Expected compensation in primary acid-base disorders.
An additional step is needed in the case of metabolic acidosis. After AG has been calculated, the “delta-delta” or “delta ratio” or “gap-gap” (three names for the same parameter) should be calculated:
where ΔΔ = delta-delta, ΔAG = AG − maximum normal AG, ΔHCO3− = normal HCO3− – HCO3−.
At our institution, maximum normal AG is 12 mmol/L and normal HCO3− concentration is 24 mmol/L, thus ΔΔ = (AG − 12)/(24 − HCO3−).
ΔΔ < 1 indicates the coexistence of an AG and a non-AG metabolic acidosis, that is, a metabolic acidosis caused by increased production of acid and by renal loss of HCO3−. This may occur in the setting of diabetic ketoacidosis.
ΔΔ > 1 indicates the coexistence of an AG metabolic acidosis and a metabolic alkalosis. This can occur in the intensive care unit in patients who have an underlying AG metabolic acidosis and are also undergoing diuresis or gastric suctioning, leading to the concurrent metabolic alkalosis.
The most common mixed acid-base disorder in surgical patients is a metabolic acidosis superimposed on a respiratory alkalosis. This occurs in patients with septic shock and hepatorenal syndrome, and also in the case of salicylate poisoning. Since the two acid-base disorders disrupt H+ homeostasis in opposite directions, the patient’s pH may be normal or near normal. Mixed respiratory acidosis and metabolic alkalosis is less common, occurring in the setting of cardiorespiratory arrest, which is a medical emergency.
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MULTIPLE CHOICE QUESTIONS
ABG: pH 7.36, Pco2 38 mm Hg, PaO2 173 mm Hg, HCO3− 20 mmol/L
CPK 125
Serum salicylate 824 mg/L (normal 30-300 mg/L)
Based on this patient’s history, examination findings and laboratory data, what is this patient’s acid-base derangement?
Urine Na 153 mmol/L Urine Cr 284 mg/dL
You suspect the cause of his orthostasis and oliguria is hypovolemia. Which of the following findings would most strongly confirm your hypothesis?
ABG 7.32/40/154/20
What is the most likely explanation for her acid-base disorder?