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most common example being water. Some of the most common physiologic electrolytes include: sodium

(Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), chloride (Cl

-), and hydrogen phosphate

(HPO4

2-). The + or – designates the charge of the ion.

In order to maintain homeostasis, the human body has a complex yet stable arrangement of

electrolytes in different concentrations in the intracellular and extracellular environments (Table 11-7).

In clinical practice, only measurements of serum values (extracellular space excluding the interstitial

space) are performed and used to infer disruptions of homeostasis, which cause organ damage. For

instance, with hyperkalemia, the serum concentration itself does not directly cause injury. It initiates

depolarization leading to impairment of cardiac conduction resulting in an end pathway of ventricular

fibrillation or asystole.

Given that serum derangements can only be discovered if lab evaluation or symptoms are present, it

is important to try to anticipate potentially life-threatening electrolyte abnormalities. This is especially

important in surgical patients in whom the loss of electrolyte-rich GI fluids occurs and can cause

predictable serum derangements (Table 11-8). For example, an infant with hypertrophic pyloric stenosis

who vomits nonbilious gastric secretions will develop a predictable hypochloremic metabolic alkalosis

due to the loss of hydrochloric acid. It is therefore of the utmost importance to recognize circumstances

that cause predictable electrolyte derangements in order to decrease the risk of morbidity and

mortality.

Table 11-7 Electrolyte Concentrations in Plasma and Intracellular Compartments

Where Sodium Goes, Water Follows

Although the relationship between sodium and water is far more complex than the above adage, there is

a distinct correlation between sodium and fluid status. This relationship can help establish both the

etiology and treatment of various derangements. For example, when thinking about hyponatremia, it is

clinically important to assess the patient’s volume status as well as check laboratory studies. These

include serum sodium, serum osmolality, and urine electrolytes. Other values such as serum glucose,

serum protein, and serum lipids may also help to differentiate hyponatremia from

pseudohyponatremia.40

Pseudohyponatremia

Marked elevations in serum lipid or protein result in a reduction in the fraction of serum that is

water/sodium and thus causes a “dilutional” hyponatremia. Examples include hyperlipidemia,

hyperproteinemia (e.g., multiple myeloma), hyperglycemia, and mannitol administration. In the case of

hyperglycemia, the serum sodium concentration should fall 1.6 mEq/L for every 100 mg/dL rise in

serum glucose concentration.

Hyponatremia

The most common pathophysiology is retention of water, which most commonly stems from oral intake

or iatrogenic use of intravenous hypotonic fluid. The body has an innate ability to produce up to 10

L/day of urine, providing an enormous range of protection against the development of hyponatremia.

However, in most surgical/trauma patients who experience hyponatremia, there is an inability to

suppress ADH, as it is normally elevated during a stress response. In this case the sodium rarely falls

below 130 mEq/L because the hyponatremia itself, as well as volume expansion, decreases the effects of

ADH on the renal collecting tubules.

Table 11-8 Electrolyte Concentrations in Gastrointestinal Secretions

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In significant cases (i.e., serum sodium <130 mEq/L) it is helpful to take a more systematic

approach. This entails assessing serum and urine osmolality as well as urine sodium (Algorithm 11-1).

Symptoms of hyponatremia occur in multiple organ systems including the CNS, GI, and

musculoskeletal (Table 11-9). In acute hyponatremia, symptoms often start when serum sodium is less

than 130 mEq/L; whereas in chronic hyponatremia symptoms typically do not occur until serum sodium

is less than 120 mEq/L.

Treatment. Treatment depends on the patient’s volume status. Hypovolemic patients are treated by

rehydration with isotonic saline, with caution not to correct serum sodium faster than 0.5 mEq/L/hr and

less than 10 mEq/L over 24 hours. If correction is faster than this rate the patient may develop central

pontine myelinolysis. This can lead to “locked in” syndrome, which consists of quadriplegia, dysarthria,

and dysphagia. In order to best prevent this rare, yet highly morbid complication, use of the following

calculation is recommended:

Na+ required (in mEq) = (Desired Na+ - Actual Na+) × TBW

TBW = 0.6 × Weight (kg)

Rapid correction with 3% or higher-concentration solutions should be avoided unless significant CNS

symptoms such as coma or seizures are present and should be done using the calculation above to

prevent overcorrection. A reasonable initial dose in an emergent situation would be 100 mL of 3%

saline given as a bolus; this can be repeated in 10 minute intervals with definite need for follow-up

laboratory evaluation to prevent overly rapid correction.

Cerebral Salt Wasting and Syndrome of Inappropriate Antidiuretic Hormone

Cerebral salt wasting (CSW) and syndrome of inappropriate antidiuretic hormone (SiADH) are both seen

in the setting of CNS disease, which is especially pertinent to trauma patients. CSW is much rarer and

typically occurs within the first 10 days of CNS insult/injury. The pathophysiology is likely related to

impaired sodium reabsorption leading to volume depletion, followed by increased ADH release causing

hyponatremia from water retention. Laboratory findings are nearly identical amongst CSW and SiADH.

Both have elevated urine osmolality compared to serum. However, CSW is associated with ECF

depletion and thus hypotension and/or elevated hematocrit, whereas SiADH patients are often net

positive in fluid balance. Given the volume status associated with CSW the treatment is usually isotonic

fluids which will suppress the release of ADH. On the contrary if isotonic fluid is given for SiADH it can

actually worsen the hyponatremia. Other options to treat CSW include salt tablets and if needed

fludrocortisone.

The initial treatment for SiADH is often fluid restriction of <800 mL/day. For more significant cases

the use of oral salt tablets or 3% hypertonic saline is recommended. Finally, vasopressin receptor

antagonists such as Conivaptan (IV) and Tolvaptan (PO) can be used; however these do carry risks such

as hepatotoxicity and can rapidly overcorrect serum sodium levels. Furthermore, they are fairly

expensive in the United States and hence should only be used in select cases.39–41

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Algorithm 11-1. Hyponatremia.

Hypernatremia

Although a less common problem in surgical patients, hypernatremia has a variety of etiologies which,

like hyponatremia can be categorized based on the patient’s volume status (Table 11-10). The most

common scenario is excessive free water loss associated with hypovolemia.

Symptoms of hypernatremia typically do not develop until serum sodium exceeds 160 mEq/L or

serum osmolality is higher than 320 to 330 mOsm/kg. Also, akin to hyponatremia the degree of acuity

is a factor. Acute hypernatremia can cause symptoms at lower levels than chronic hypernatremia. The

majority of symptoms experienced are CNS related with early signs being irritability, restlessness, and

spasms. Later symptoms include ataxia and seizures.

The treatment of hypernatremia, like hyponatremia should not occur too rapidly, otherwise

complications can ensue. A rate >0.7 mEq/L is considered dangerous as it can lead to cerebral edema

and brainstem herniation. The most judicious way to correct hypernatremia involves calculating the free

water deficit to obtain a desired sodium level.

Table 11-9 Symptoms of Hyponatremia

Water requirement = (Desired change in Na+ × TBW)/Desired Na+

TBW = 0.6 × Weight (kg)

A caveat to this equation is that it does not take into account ongoing free water losses such as urinary

or GI loss. Further calculations can be done to quantify urine losses if this is a major concern.

Table 11-10 Causes of Hypernatremia

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Algorithm 11-2. Acute hyperkalemia.

Potassium

Potassium is the most abundant intracellular cation with a normal intracellular concentration of 150

mEq/L as opposed to an extracellular level ranging from 3.5 to 5 mEq/L. This large gradient produces a

strong membrane potential especially in cardiac, skeletal, and smooth muscles. The overall potassium

balance is determined by potassium intake and renal/extrarenal excretion. Renal excretion accounts for

90% of excreted potassium. Thus, renal failure leads to hyperkalemia. Humoral factors such as

aldosterone, vasopressin, and β-agonists stimulate renal excretion of potassium. Intracellular shifting is

another strong causative agent for extracellular potassium change. For instance, insulin and alkalosis

both cause K+ to shift intracellular, one for glycolysis, the other in exchange for H+ as a buffer.

Conversely, acidosis causes K+ to shift extracellular in exchange for H+, again to buffer serum pH.

Hyperkalemia

Renal insufficiency is the leading cause of hyperkalemia in surgical patients. Hyperkalemia can occur

even in the setting of nonoliguric renal failure. Potassium-rich intravenous fluids, especially blood

transfusions can also lead to hyperkalemia. Disease processes associated with cellular injury such as

crush injuries, reperfusion syndrome, tumor lysis syndrome, and burns are all potential causes of

hyperkalemia. Additionally, medications such as succinylcholine and ACE inhibitors can worsen existing

hyperkalemia.

Regardless of the etiology, the common pathway for clinical manifestations is dysfunctional

membrane depolarization, the most lethal scenario effecting cardiac membrane depolarization. On an

electrocardiogram (EKG) this can be seen in the mildest form with peaked T waves, in a more severe

state with flattened P waves, prolongation of the QRS, or deep S waves. The final pathway can yield

ventricular fibrillation with or without cardiac arrest.

The initial medication of choice for hyperkalemia is intravenous calcium for membrane stabilization,

which lasts approximately 30 to 60 minutes. Subsequent therapy can include insulin coadministered

with dextrose, β2 agonist, and sodium bicarbonate, which are designed to shift extracellular potassium

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into the intracellular space. Resin-binding agents such as Kayexalate act to decrease potassium

absorption and thus are more important in the management of chronic hyperkalemia.42,43 Loop diuretics

can assist by promoting renal potassium excretion, but should only be used if the patient is not

hypovolemic. A last resort in situations of complete renal failure or critical levels of potassium is

hemodialysis. The treatment utilized depends upon the laboratory value, but more importantly the

clinical scenario and EKG findings (Algorithm 11-2).

Hypokalemia

Similar to hyperkalemia, manifestations of hypokalemia result from the disturbance in the gradient

between intracellular and extracellular potassium. The reference level of 3.5 mEq/L is often cited as the

lowermost level of normal serum potassium. Below this level minor disturbances including intestinal

ileus, premature ventricular complexes, and nonfatal arrhythmias can occur. Severe cardiac and muscle

manifestations often do not occur until levels fall below 2.5 mEq/L. Findings at this dangerous level

include significant muscle weakness and major EKG changes. Possible changes include prolonged QT,

flattened T waves, ST depression, prominent U waves, and most dangerously ventricular arrhythmias.

Initial treatment consideration must include elucidation of possible etiologies (Table 11-11); certain

etiologies are especially important, as without correction of the underlying cause, the hypokalemia

itself may not be correctable. Examples of this include hypomagnesemia, acute alkalosis,

hyperaldosteronism, and mucus secreting villous adenoma. The mainstay of initial treatment for

hypokalemia is enteral or intravenous potassium replacement. If the patient is symptomatic, then the

replacement or at least a portion of it should be given intravenously to achieve a more rapid effect.

Limiting the rate of intravenous potassium infusion is necessary to prevent caustic injury to veins.

Maximal recommended rates include 10 to 20 mEq/hr via a peripheral IV or up to 40 mEq/hr via

central access.

Table 11-11 Causes of Hypokalemia

Figure 11-6. Effects of hypocalcemia (A) and hypercalcemia (B) on the mediators of calcium homeostasis. PTH, parathyroid

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hormone.

Calcium

Calcium (Ca2+) is essential for human life. Calcium participates in numerous processes including cardiac

membrane depolarization, muscle contraction, enzymatic reactions, coagulation, and formation of

bone/teeth. Approximately 99% of total body calcium is located in bone. Ionized calcium, which makes

up approximately 45% of total calcium, is responsible for most of the physiologic actions of calcium in

the body. Normal serum concentration of ionized calcium is approximately 4.5 mg/dL and this level is

tightly regulated. Both pH and plasma protein level can affect the proportion of calcium in the ionized

state. A change in albumin concentration of 1 g/dL changes protein-bound calcium by 0.8 mg/dL in the

same direction. The fundamentals of the regulation of calcium homeostasis are depicted in Figures 11-6

and 11-7. The effect of pH on calcium will be discussed later in this chapter.

Hypercalcemia

The most common causes of hypercalcemia are hyperparathyroidism and malignancy (Table 11-12).44,45

Primary hyperparathyroidism occurs when one or more parathyroid glands inappropriately produce

increased amounts of PTH. Parathyroid adenomas are responsible for ∼85% of cases. Chief cell

hyperplasia accounts for an additional 15% of cases, while parathyroid cancer is the cause in less than

1% of cases of primary hyperparathyroidism.

Secondary hyperparathyroidism occurs when there is elevated PTH due to another organ system,

namely renal failure. This occurs because of poor renal excretion of phosphate and decreased intestinal

absorption of calcium secondary to impaired renal hydroxylation of vitamin D.

Tertiary hyperparathyroidism is parathyroid hyperplasia with autonomous PTH production. Most

commonly, patients who had renal failure with secondary hyperplasia then undergo renal transplant and

still have hypercalcemia. This occurs in up to 30% of patients with prerenal transplantation

hyperparathyroidism (Table 11-13).

Figure 11-7. Vitamin D synthesis.

Table 11-12 Other causes of Hypercalcemia

Regardless of cause, hypercalcemia has characteristic clinical manifestations that affect various organ

systems. Classically taught as “stones, moans, and psychiatric undertones,” meaning renal,

abdominal/GI, and neuropsychiatric manifestations (Table 11-14). The earliest symptoms are usually

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