Journal of Parenteral and Enteral Nutrition

http://pen.sagepub.com/ Fluid and Electrolyte Management : Putting a Plan in Motion

Kristen M. Rhoda, Mary Jo Porter and Cristiano Quintini JPEN J Parenter Enteral Nutr 2011 35: 675 DOI: 10.1177/0148607111421913 The online version of this article can be found at: http://pen.sagepub.com/content/35/6/675

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Tutorial

Fluid and Electrolyte Management: Putting a Plan in Motion

Kristen M. Rhoda, MS, RD, CNSD1; Mary Jo Porter, RD, CNSC1; and Cristiano Quintini, MD1
Financial disclosure: none declared. Fluid and electrolyte management is challenging for clinicians, as electrolytes shift in a variety of settings and disease states and are dependent on osmotic changes and fluid balance. The development of a plan for managing fluid and electrolyte abnormalities should start with correcting the underlying condition. In most cases, this is followed by an assessment of fluid balance with the goal of achieving euvolemia. After fluid status is understood and/or corrected, electrolyte imbalances are simplified. Many equations are available to aid clinicians in providing safe recommendations or at least to give a starting point for correcting the abnormalities. However, these equations do not take into consideration the vast differences between clinical scenarios, thus making electrolyte management more challenging. The

Journal of Parenteral and Enteral Nutrition Volume 35 Number 6 November 2011 675-685 2011 American Society for Parenteral and Enteral Nutrition 10.1177/0148607111421913 http://jpen.sagepub.com hosted at http://online.sagepub.com

supplementation plan, whether delivered intravenously or orally, must include an assessment of renal and gastrointestinal function, as most guidelines are established under the assumption of normal digestion, absorption and excretion. After the plan is developed, frequent monitoring is vital to regain homeostasis. A fluid and electrolyte management plan developed by a multidisciplinary team is advantageous in promoting continuity of care and producing safe outcomes. (JPEN J Parenter Enteral Nutr. 2011;35:675685) Keywords: electrolytes; fluid; multidisciplinary team; osmolality; hyponatremia

Preface
Learning fluid and electrolyte management as a dietitian was a complex undertaking. Attempting to remember all of the information from biochemistry textbooks and internship preceptors seemed impossible when I encountered my initial real life scenario. Following the steps laid out for me as a student helped, but it was the expertise shared from physicians, pharmacists, nurses, and dietitians within the multidisciplinary team that advanced my knowledge. Tackling a potassium (K) imbalance is never as simple as administering a K bolus. Treatment requires understanding the pathophysiology of the disease or condition that leads to the imbalance with the assistance of the physician, applying the principles of pharmacokinetics with the support of the pharmacist, understanding medication delivery tactics and vascular access selection criteria with the aid of the nurse, and applying nutrient absorption and
From the 1Intestinal Rehabilitation and Transplant Program, Center for Human Nutrition, Cleveland Clinic, Cleveland, Ohio. Received for publication July 23, 2011; accepted for publication August 9, 2011. Address correspondence to: Kristen M. Rhoda, MS, RD, CNSD, Intestinal Rehabilitation and Transplant Program, Center for Human Nutrition, Cleveland Clinic, 9500 Euclid Ave/A100, Cleveland, OH 44195; e-mail: kristen.rhoda@gmail.com.

metabolism with the help of the dietitian. Our Intestinal Rehabilitation and Transplant Program represents a referral center for patients with advanced and complex intestinal failure. Chronic diarrhea, dehydration, electrolyte abnormalities, micronutrient imbalances, and malnutrition exist often in the context of renal dysfunction, ongoing inflammatory state, and the result of a major gastrointestinal (GI) anatomical derangement (just as in combinatorial mathematics, in which a derangement is a permutation of the elements of a set such that none of the elements appear in their original position). Whether the patient is on specialized nutrition support or taking in a modified diet, using the skills provided by the multidisciplinary team assists in my ability to dissect operative reports, interpret GI and vascular imaging studies, assess medication history, and determine the underlying etiology of malabsorption. This approach is, in my opinion, the single most important determinant for success.

Introduction
Fluid and electrolyte management is challenging to most clinicians, as each clinical picture is ever changing. The following article summarizes the primary function and regulatory mechanism of each electrolyte. Assessment tactics and treatment guidelines are also reviewed. The purpose of this article is to provide a thorough review of
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676 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, November 2011

Table 1. Useful Equations in Calculation of Fluid and Electrolyte Needs1,4-8

Sodium deficit or excess (mEq) Normal TBW Current TBW
a

= (140-serum Na) TBW = 0.6 kg body weight = (normal serum Na TBW)/Measured serum Na = sodium excess/140 = (2 serum Na) + (serum urea mg/dL/2.8) + (blood glucose mg/dL/1.8) = (*mEq/L serum Na)/TBW + 1 Example: = (154 mEq/L 123)/41.9 = 0.74 mEq change in serum sodium with 1 L NS infusion = blood glucose (mg/dL) 0.016 + serum Na = Mg in mEq/L + 0.005 (40 albumin g/L) = ([4 serum albumin (g/dL)] 0.8) + measured calcium (mg/dL) = 12.5% increase in fluid needs for each degree >37C

Amount of water needed to return serum Na to 140 mEq Serum osmolality (mOsm/kg) Change in serum Na concentration with 1 L of IVF solution *= mEq of Na/L of solution Example: 1L 0.9% NS = 154 mEq/L Prediction of serum sodium for hyperglycemia Corrected Mg Corrected Ca Prediction of fluid requirements for fever
a

Ca, calcium; K, potassium; Mg, magnesium; NS, normal saline; Na, sodium; TBW, total body water. Formula underestimates the TBW deficit in cases with hypotonic fluid loss requiring additional Na and K repletion.

fluids and electrolytes. As with most topics within clinical practice, additional reading is encouraged to improve baseline knowledge of electrolyte management.

Water
Water is a major component of the human body. Total body water (TBW) constitutes approximately 45%60% of body weight and is divided into extracellular fluid (ECF) and intracellular fluid (ICF) compartments.1 ICF accounts for two-thirds of TBW, which accounts for up to approximately 40% of body weight, with the remaining one-third of TBW being ECF, accounting for approximately 20% of body weight.1 ECF encompasses intravascular fluid, interstitial fluid, and transcellular fluid (contained within certain body cavities).2 Examples of transcellular fluid include GI, cerebrospinal, pleural, and intraocular fluids. Although transcellular fluid makes up only a small portion of fluid in adults (1 L), it accounts for a great amount of water movement in and out of the transcellular fluid.1-3 Water moves between the ICF and ECF compartments depending on the amount of solutes present until it reaches a state of equilibrium. The measurement of this movement is referred to as osmolality and is often used interchangeably with tonicity. Osmolality is measured in milliosmoles per kilogram (mOsm/kg) of water. The osmolality of body fluids and isotonic fluids is approximately 280300 mOsm/kg. Assessment of serum and urine osmolality can guide the treatment of TBW imbalances (see Table 1). Water excretion is primarily regulated through glomerular filtration, tubular reabsorption and

secretion, and water conservation within the nephron loop.9 TBW loss occurs through urine (5001,500 mL/d), GI losses (100200 mL/d), skin (300 mL/d), and the respiratory tract (400 mL/d).2,10 Understanding normal TBW loss is important when calculating the estimated fluid requirements. Following is an example of estimated fluid requirements for an adult with normal renal function.2 A 46-yearold man with an average ileostomy output of 1,800 mL, 1,000 mL oral fluid intake, and 2,000 mL intravenous fluid (IVF) per day, over the past week, with a Tmax of 38.5C. Daily fluid requirements are: + 1,500 mL for urine + 1,800 mL for stoma output + 500 mL insensible + 500 mL fever (see Table 1) 1,000 mL oral intake 2,000 mL IVF provision = 1,300 mL estimated fluid requirements Hypovolemia. Hypovolemia, defined as an ECF deficit, may occur as a decrease in water volume, with or without an electrolyte deficit.1,3 Hypovolemia as a water deficit alone is usually the result of an inability to regulate water intake (eg, lost of the thirst mechanism or concentrated enteral nutrition). Pathognomonic signs of hypovolemia include thirst, dizziness, hypotension, tachycardia, poor skin turgor, and decreased urinary sodium (Na) concentration (<15 mEq/L).1 Chemical abnormalities reveal hypernatremia; however serum Na levels do not reflect total Na levels but rather serve as an indicator of the

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Fluid and Electrolyte Management / Rhoda et al 677

Table 2. Commonly Used Intravenous Fluids

Source NS D5W D5, 0.45NS D5, 0.9NS LR D5, LR Na 154 0 77 154 130 130 Cl 154 0 77 154 109 109 K+ 0 0 0 0 4 4 Lactate 0 0 0 0 28 28 Dextrose 0 50 50 50 0 50 mOsm 280300 250 400 560 270 525

Cl, chloride; D5, 5% dextrose solution; D5W, 5% dextrose solution in water; K, potassium; LR, Lactated Ringers; Na, sodium; NaCl, sodium chloride; NS, normal saline.

osmolality of the serum.1,3,10 In this scenario, treatment is aimed at replacing water, with the goal of regaining Na homeostasis and serum osmolality. IVF replacement should be administered as 5% dextrose in water,11 or in the case of (orthostatic) hypotension, a hypotonic solution should be given (see Table 2). Hypovolemia, with a combined water and electrolyte deficit, is the result of excessive losses (eg, GI losses, diuretic therapy, or postoperative fluid sequestration). Chemical abnormalities are not as reliable in this scenario and will vary depending on the type of fluid loss. Volume depletion results in decreased urinary Na concentration (<10 mEq/L), increased plasma osmolality (driven by hypernatremia), and increased urine osmolality (>450500 mOsm/kg).1 Elevated plasma osmolality stimulates the secretion of antidiuretic hormone (ADH) to increase water reabsorption in the renal tubules. The calculation of Na and volume deficit determines the need for fluid and electrolyte replacement. An isotonic solution such as normal saline (NS) is often indicated in these cases.1,11 ADH is one of 6 hormones that affect water and electrolyte balance. Others include angiotensin II, aldosterone, cortisone, epinephrine, and norepinephrine. ADH is an arginine vasopressin produced in the pituitary gland, which controls renal excretion and reabsorption of water. Osmoreceptors located in the hypothalamus are sensitive to changes in serum osmolality and trigger the release or suppression of ADH upon detection of hyperosmolality and hypoosmolality, respectively. Upon detection of hyperosmolality, ADH is released, alerting the kidney to reabsorb water, which subsequently decreases serum osmolality.12 Excessive water reabsorption leads to hypoosmolality, and the osmoreceptors respond by shutting off ADH secretion. Secretion of ADH during hypoosmolality and normal blood volume is referred to as the syndrome of inappropriate ADH hypersecretion (SIADH). SIADH results in increased reabsorption of water, leading to worsened hypoosmolality, hyponatremia, and hypotension.12 SIADH develops in response to central nervous system diseases, stress response during the postoperative period, and pulmonary diseases.3,12 It is diagnosed based on the clinical findings of hyponatremia, serum hypoos-

molality, euvolemia, and urinary hyperosmolality (>100 mOsm/kg of water), in the presence of normal thyroid and adrenal function.12 Treatment should be aimed at correcting the primary problem, along with water restriction and Na replacement. Vasopressin-receptor antagonists are also used to help inhibit the action of ADH.3,12 Hypervolemia. Hypervolemia is defined as ECF volume expansion, and may occur due to altered renal function, excessive fluid administration, interstitial to plasma fluid shift, or post-operative stress response.1,3 Hypovolemia is often seen after surgery and anesthesia, as ADH is released, resulting in water retention by the kidneys. This condition may be worsened by heart failure, hypoalbuminemia, and liver or renal disease.1 Pathognomonic signs of hypervolemia include edema, increased body weight, jugular venous distention, tachypnea, and hypertension.1-3 Chemical abnormalities reveal hyponatremia and hypo-osmolality, requiring Na restriction to prevent worsening water retention. If the patient is hypervolemic and hyponatremic, both free water and Na should be restricted.1 In some cases, the use of diuretics can aid in mobilization of fluid.13

Na
Na is found predominantly in ECF and strongly contributes to osmolality and the regulation of acid-base balance.1,3,5 Plasma Na concentration does not reflect total body Na but is an indicator of extracellular volume status.2 Na balance is regulated by the kidney through the excretion and reabsorption of Na and water in the distal tubule and loop of Henle.6 Hyponatremia. Hyponatremia (plasma [Na+] <135 mEq/L) may be classified as either hypotonic (dilutional) or non-hypotonic.14 Nonhypotonic hyponatremia may result from a shift of fluid out of cells and into ECF, resulting in serum hyperosmolarity and dehydration of the cells. The most common form of hyponatremia is hypotonic (dilutional) hyponatremia due to an excess of

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678 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, November 2011

Table 3. Presentation of Electrolyte Depletion With Corresponding Pathophysiology7,10,14,15

Signs and Symptoms Calcium 1.  Hyperactive reflexes, light-headedness, irritability, seizures, hyperventilation 2. Tetany, numbness with tingling of fingers 1. 2. 3. 4. 5. 6. 7. Confusion, seizures, coma Chest pain Difficulty breathing Weakness Bone pain Bruising, bleeding Respiratory dysfunction Pathophysiology 1.  Due to increased excitability of nerve and muscle cells 2.  Due to spontaneous skeletal muscle contractions that occur repeatedly 1. Reduced oxygenation of the myocardium 2.  Cardiac muscle has less ATP, which decreases cardiac output and BP and increases pulmonary wedge pressure 3. Decreased 2,3-diphosphoglycerate and ATP in RBC 4.  Lack of P and ATP in muscle causing less strength with muscle contraction 5.  Changes in P and ATP deficits increase bone resorption and osteomalacia and lower bone Ca, P, Mg 6. Due to platelet dysfunction 7.  Decreased availability of phosphate-containing energy sources  ncreased update of calcium causing tension of 1. I vascular smooth muscle 2. CNS changes Increased update of calcium causing tension of 3.  vascular smooth muscle 1. Related to serum osmolality changes in the CNS

Phosphorus

Magnesium

1. Weakness, lethargy, muscle cramps 2. Mood changes, confusion 3. Vomiting, decreased cardiac output

Sodium

1. Nausea, vomiting, headache, muscle cramps, disorientation, weakness, lethargy, confusion, dizziness, seizure, coma, death 1. 2. 3. 4. Constipation Weakness Lethargy ECG abnormalities

Potassium

1. Caused by smooth muscle weakness 2. Due to an increased ratio of intra- to extracellular K

ATP, adenosine triphosphate; BP, blood pressure; Ca, calcium; CNS, central nervous system; ECG, electrocardiogram; K, potassium; Mg, magnesium; P, phosphorus; RBC, red blood cell.

water.14 Hyperglycemia may worsen hyponatremia, by increasing serum osmolality, which in turn generates a shift of water into the ECF, thus decreasing serum Na concentration. Hyperglycemia decreases serum Na by 1.7 mEq/L when hyperglycemia exceeds 100 mg/dL14 (see Table 1). Hypokalemia may also worsen hyponatremia because of the extracellular and intracellular ratio required to maintain homeostasis.14 Treatment of hyponatremia starts with water restriction and should be guided by the severity of symptoms (see Tables 3 and 4) and evaluation of the length of time in which hyponatremia developed (see Table 1). Acute onset of hyponatremia, occurring in <48 hours, requires correction of serum Na with isotonic IVF (e.g., NS) at a rate of 12 mEq/L/h. Patients with severe symptoms such as seizures or mental changes, along with concentrated urine >200 mOsm/kg and plasma Na <120 mEq/L, who are euvolemic or hypervolemic require serum Na corrected at a rate of 12 mEq/L/h using hypotonic saline (eg, NS).14 Chronic hyponatremia, occurring over 23 days or longer, should be given isotonic IVF to correct serum Na at a rate of 0.5 mEq/L/h while monitoring

serum Na to not exceed 812 mEq/L in 24 hours (see Table 1). As a general rule, approximately 50% of the estimated Na deficit should be given in the first 24 hours, with the remainder given over the next 2472 hours. Goals for treatment should not exceed a rise in serum Na >135 mEq/L with initial correction, and for severe hyponatremia (<105 mEq/L), the goal is to reach a serum Na level of 120130 mEq/L (see Table 1). Lab monitoring of serum Na should occur every 24 hours when the patient is symptomatic and every 48 hours when asymptomatic.2,7 Slow treatment of hyponatremia is crucial in preventing osmotic myelinolysis (see Tables 3 and 4).16 Hypernatremia. Hypernatremia (>145 mEq/L) is usually due to a water deficit leading to cellular dehydration but may also result from excessive Na, which is usually a result of iatrogenic Na administration.4 Treatment begins with an evaluation of body water deficit (see Table 1). Acute hypernatremia requires rapid correction with a decrease in plasma Na concentration of 1 mEq/L/h.5 In chronic hypernatremia, treatment should be aimed at lowering plasma Na at a rate of 0.5 mEq/L/h, with a

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Fluid and Electrolyte Management / Rhoda et al 679

Table 4. Presentation of Elevated Electrolytes With Corresponding Pathophysiology5,10

Signs and Symptoms Calcium 1. Anorexia, nausea, vomiting 2. Polyuria, stones, nocturna, uremia 3. Confusion, coma, incontinent 4. Weakness, fatigue 1.  Anorexia, nausea, vomiting, oliguria, corneal haziness, conjunctivitis 2. Tetany 3. Hypocapnia 4. Hyperactive reflexes 5. Tachycardia 6. Muscle weakness 1. Nausea, vomiting, diaphoresis, muscle weakness 2. Altered mental status, coma, lethargy, confusion 1. Increased thirst, fatigue, restlessness, muscle irritability, seizures, coma, death 1. Muscle weakness, flaccid paralysis 2. ECG changes 3. Muscle cramping 4. Arrhythmias Pathophysiology 1. 2. 3. 4. 1. 2. 3. Decreased activity of the gastrointestinal muscles Decreased activity of urinary muscles Decreased CNS activity Due to decreased activity of nerve and muscle cells Metastatic calcifications Hypocalcemia Hypoxemia

Phosphorus

Magnesium Sodium Potassium

1. Neuromuscular 2. Central nervous system 1. Related to serum osmolality changes in the CNS 1. Decreased ratio of intra- to extracellular K 2.  Repolarization of the ventricles and depolarization of the atria and ventricles

CNS, central nervous system; ECG, electrocardiogram; K, potassium.

maximum decrease of 10 mEq/L/d. Serum Na reduction should not exceed 1 mEq/L/h, or cerebral edema and death may result (see Table 1).2,3

K
K is the primary intracellular cation, with only 2% of total body K (TBK) remaining in the ECF. Cellular metabolism, specifically protein and glycogen synthesis, depends on sufficient intracellular K concentration. Optimal TBK promotes neuromuscular and cardiac function as well. Maintaining an intracellular to extracellular ratio of approximately 30:1 is essential to life, as a 1.5%2% variation can lead to fatal consequences.6 Because of this precise balance of K in the ICF and ECF, both renal and nonrenal mechanisms contribute to the maintenance of TBK. The kidneys play a major role in maintaining K homeostasis. Renal K secretion takes place in the distal nephron and is driven by aldosterone balance.1 Although many factors drive aldosterone secretion, the effect of serum K levels on aldosterone secretion is significant. As K concentration climbs, aldosterone secretion increases, causing the distal tubule and collecting duct to reabsorb Na and secrete K.1 The opposite occurs in the presence of hypokalemia. Medications, especially diuretics and nephrotoxic drugs, can affect urinary K excretion and therefore should be adjusted accordingly during a K imbalance.1,6,17 While the kidney is the main regulatory organ for maintaining K homeostasis, nonrenal mechanisms such as hormones, pH, osmolality, and adaptation also play an

important role. It is well known that insulin secretion promotes the movement of K from the ECF to the ICF, but the mechanism is the subject of continued debate.1 This is particularly relevant in refeeding syndrome, as an insulin surge after the reintroduction of nutrition in a severely malnourished patient leads to life-threatening hypokalemia.18-20 In acidosis, hydrogen ions move into the ICF to be buffered, which forces K, an equivalent cation, into the ECF.1 Therefore, as pH changes, there is a reciprocal change in K. Osmolality is another driving force for maintaining K balance, as an elevated plasma osmolality causes fluid to shift into the ECF.1 This shift increases the intracellular K content, which leads to hyperkalemia. Lastly, K adaptation refers to the ability to decrease cellular uptake, when excessive exogenous K is given, and/or when TBK is elevated.1 This adaptation is a preventative measure against the development of life-threatening hyperkalemia. The dietary reference intake (DRI) for adults >18 years of age is established at 4.7 g/d and at 12 mEq/kg/d for parenteral nutrition (PN)dependent individuals and then adjusted as needed.6 The small intestine absorbs approximately 90% of dietary K, and a trivial amount of K absorption occurs in the colon.21 After dietary K is absorbed, the kidneys regulate urinary excretion and reabsorption. Hypokalemia. Assessing hypokalemia (serum K <3.5 mmol/L) is also a complex task since many factors contribute to its imbalance. In addition to assessing renal function, medications, and exogenous intake, magnesium (Mg) status should also be assessed. Mg plays a vital role in the maintenance of the Na-K adenosine triphosphate

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680 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, November 2011

(Na-K-ATPase) pump, which regulates the intracellular to extracellular K ratio.22 In cases of hypokalemia with concurrent hypomagnesemia, Mg levels must be repleted prior to correcting the K imbalance.6,15,22 As with hyperkalemia, dietary intake is rarely the cause of the hypokalemia, and therefore, increasing dietary intake is unlikely to improve serum K levels. Treatment should be based on 2 factors: the presence of symptoms (see Tables 3 and 4) and serum K levels (see Table 5). Oral K supplementation is appropriate for asymptomatic, mild hypokalemia (K 3.23.5 mmol/L). Symptomatic and/ or severe hypokalemia (K <3.0 mmol/L) requires intravenous (IV) supplementation. In either case, medications, which may be contributing to excessive urinary K losses (eg, furosemide), should be adjusted. Potassium chloride (KCl) is preferred for correction of alkalosis or improvement of extracellular volume expansion. In cases of acidosis, potassium acetate may be a better choice. Hyperkalemia. Assessing hyperkalemia (serum K >5 mmol/L) is challenging, but its difficulty can be lessened if handled in a systematic way. First, pseudohyperkalemia should be ruled out prior to any treatment. Pseudohyperkalemia is defined by the presence of hemolysis, extreme leukocytosis, or thrombocytosis resulting in false hyperkalemia.26 After pseudohyperkalemia is ruled out, renal function, medications, and exogenous intake need to be assessed prior to treatment. Treatment for hyperkalemia starts with the reduction of dietary K and promotion of optimal urinary output (>1,000 mL/d). Medications that could be contributing to decreased urinary K excretion (eg, spironolactone, nonsteroidal anti-inflammatory drugs, heparin, -blockers, and digitalis; see Table 5) require adjustment. Persistent hyperkalemia requires the use of a resin (eg, Na polystyrene sulfunate) to produce a cathartic effect.17 Caution must be taken when using a resin to prevent rebound hypokalemia, as the K may take several hours to normalize. For life-threatening levels (K >8.0 mmol/L), institutional algorithms for the use of calcium (Ca), bicarbonate, dextrose with insulin, and hypertonic saline to correct hyperkalemia should be followed (see Table 5).

evaluation methods.27 Approximately 25% of Mg is protein bound, bringing to question the possible benefit of using ionized Mg levels and/or using an equation for hypoalbuminemia (see Table 1). Despite conflicting reports, serum ionized Mg has not yet proven to be a superior method of detecting Mg deficiency and/or predicting clinical outcomes.27 The Mg tolerance test involves the measurement of 24-hour renal excretion, before and after PN Mg administration. Retention of >20% of Mg indicates a deficiency.27 Although this test is considered accurate, it is not realistic in hospitalized patients because of the complexity of collecting urinary samples. Mg absorption is primarily regulated by GI and renal mechanisms.10 The DRI for adults >18 years of age is 410420 mg/d for men, 310360 mg/d for women,28 and approximately 820 mEq/d6 for PN-dependent individuals. Approximately 30%40% of dietary Mg is absorbed by the GI tract, and the remainder is excreted in stool. GI absorption occurs primarily in the jejunum and ileum, with some absorption also occurring in the colon.15,27 Intestinal absorption may be reduced by excessive zinc, vitamin B6, oxalates, and free fatty acids.15,27 Hypomagnesemia blocks the release of Ca from within the cell and impairs the secretion of parathyroid hormone (PTH), both of which lead to hypocalcemia.10,29 Mg is necessary for intracellular and extracellular movement of K via the Na-K-ATPase pump; thus, Mg levels should be corrected to subsequently enable repletion of K and Ca.15 Mg excretion is a function of the kidney, with most reabsorption occurring in the ascending loop of Henle.15,27 The kidneys have the ability to conserve Mg during states of deficiency. It is important to understand that the maximum tubular reabsorption in the loop of Henle decreases with an increased Mg load. Tubular reabsorption is dependent on serum Mg levels, the Mg dose, and Mg infusion.10 Within the proximal tubule, hypercalcemia results in an increased excretion of Mg,27 while phosphate depletion prevents reabsorption within the ascending limb and distal tubule.15 Hypomagnesemia. Hypomagnesemia (<1.5 mEq/L) develops in a variety of settings, including increased GI or urinary losses, chronic alcohol abuse, and hyperaldosteronism.1,3,27 Hypomagnesemia is also seen during refeeding syndrome, due to intracellular shifting of Mg, total body depletion, and increased demand of Mg for anabolism.18 Treatment is determined based on the presence of symptoms (see Tables 3 and 4) and on the serum level. Oral supplementation is warranted with mild Mg (defined as 1.11.4 mg/ dL). Symptomatic or severe hypomagnesemia (<1 mg/dL) should be replaced with 3264 mEq of IV Mg. Oral supplementation with Mg salts is available in a variety of preparations. Caution must be taken as large doses of oral Mg and, in particular, Mg oxide salts have been shown to increase osmotic load, resulting in diarrhea.6

Mg
Mg is the second most abundant intracellular cation. Total body Mg is present in bone (60%65%), skeletal muscle (20%), and nonmuscular tissue (11%), leaving only a small amount of interchangeable Mg (<1%) within the ECF.15 Mg functions in >100 enzymatic reactions and is involved in cellular energy metabolism.1,15 Serum Mg is a poor indicator of total body stores yet remains the standard measurement because of the complexity of alternative

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Fluid and Electrolyte Management / Rhoda et al 681

Table 5. Treatment Considerations for Electrolyte Abnormalities6,7,17,23-25

Electrolyte Calcium Elevation Oral Low-calcium diet Reduce vitamin A, vitamin D, and/or calciumcontaining antacids IV Start NS at 200300 mL/h; may need to start furosemide IV when rehydrated Oral Low-phosphorus diet Phosphate binders IV Assess the need for volume repletion Dialysis may be needed in severe cases Depletion Oral 1,0001,500 mg/d IVb (tetany present) 1020 mL of 10% calcium gluconate IV over 4 hours

Phosphorus

Magnesium

Sodium

Oral Remove magnesium-containing medications Consider starting diuretics IV (severe >12.532 mg/dL) Start 10 mL of a 10% calcium gluconate solution in severe cases 7.8-13.6 mEq Ca via central infusion over 510 minutes or 4.5612.7 mEq Ca peripherally over 310 minutes Oral Low-sodium diet Increase oral fluid intake IV Decrease or discontinue administration of sodium with replacement of water deficit

Potassium

Oral Low-potassium diet Remove potassium-sparing medications Consider use of diuretics IV (nonsymptomatic) Sodium bicarbonate (50100 mEq) Dextrose infusion (25100 g with 510 units insulin) IV (symptomatic) Calcium gluconate (12 g)

Oral (mild replacement) Increased dietary intake or Consider phosphate-containing multivitamin IV (moderate replacement) Oral supplementation: 2.53.5 g/d in divided doses 0.320.64 mmol/kg IV (max 30 mmol Na3PO4) slowly over 6 hours IV (severe replacement) 1 mmol/kg IV (max 80 mmol Na3PO4) slowly over 812 hours Oral (mild) Increase dietary intake Oral supplementation (eg, magnesium lactate) IV (moderate) 832 mEq (max 1.0 mEq/kg) slowly with 8 mEq over 12 hours daily IV (severe <1 mg/dL) 3264 mEq (max 1.5 mEq/kg) slowly with 8 mEq over 12 hours daily Oral Consider free water restriction IV (mild to moderate) Consider free water restriction Provision of NS and/or NS (correct at a rate of 12 mEq/L/h) IV (severe) 3% sodium chloride (correct at a rate of 12 mEq/L/h) Oral Increase dietary intake and/or add salt substitutes Oral supplementation: 40100 mEq daily in divided doses IVa (mild) 40 mEq PO 1 or 10 mEq IV over 1 hours 34 doses IVa (moderate) 20 mEq PO every 2 hours 3 doses or 10 mEq IV over 1 hour 4 doses, recheck and repeat as needed IVa (severe) 40 mEq IV over 24 hours, recheck and repeat as needed or 40 mEq IV over 4 hours as needed

Ca, calcium; IV, intravenous; Na3PO4, sodium phosphate; NS, normal saline; PO, per os. a Not to exceed 20 mEq/h. b Not to exceed 0.81.5 mEq/min.

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682 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, November 2011

Hypomagnesemia is most commonly treated intravenously because of the known GI intolerance of oral Mg1 (see Table 5). Hypermagnesemia. Hypermagnesemia (>2.5 mEq/L) may be the result of excessive supplementation, renal disease, laxative abuse, or increased intake of Mg-containing antacids.1,3,27 Treatment for hypermagnesemia includes dietary restriction, elimination of Mg-containing medications, and the use of diuretics and dialysis for severe cases (see Table 5). In severe, symptomatic hypermagnesemia (>12.532 mg/dL), 7.813.6 mEq of Ca over 510 minutes should be infused via central line.7 If volume status allows, treatment may include provision of NS with IV furosemide to enhance urinary excretion of Mg.10

PN-dependent individuals, with adjustments as needed. Oral supplementation is better absorbed when taken with a meal to improve the solubility of the Ca salts. Na and protein intake is proportionately related to Ca excretion in the urine and ultimately to bone loss.31,32 Fortunately, the P content of dietary protein augments this hypercalciuric effect of proteins. Regardless of dietary content, absorption is dependent on adequate GI and renal function. Hypocalcemia. Hypocalcemia can be defined in the presence of a normal albumin level, as a serum Ca <8.5 mg/ dL. Nearly 50% of serum Ca is protein bound, and therefore, in the presence of hypoalbuminemia, a corrected Ca, or preferably ionized Ca, should be used10 (see Table 1). True hypocalcemia increases PTH production and vitamin D activation in an effort to regain homeostasis. Elevated PTH increases renal P excretion, mobilizes skeletal Ca, and enhances Ca absorption in the GI tract through activation of vitamin D. Increased renal P excretion results in decreased serum P levels, which drives the extracellular movement of Ca. Treatment of hypocalcemia depends on the Ca level and the presence of symptoms (see Tables 3 and 4). If the serum Ca level is >7.5 mg/dL and/or there is an absence of symptoms, dietary intake should be optimized, and oral supplementation should be considered (see Table 5). Although true hypocalcemia is usually unrelated to dietary sources, this treatment option should be exhausted as the first-line therapy. Symptoms begin to develop as levels drop below 7.5 mg/dL. In these cases, IV supplementation is necessary. In the presence of hypomagnesemia or hyperphosphatemia, Mg and P levels will need to be corrected prior to the replacement of Ca. Hypercalcemia. Hypercalcemia (>10.5 mg/dL) develops in the setting of bone catabolism, resulting in an increased movement of Ca into the ECF. This is precipitated by immobilization, malignancies, and primary hyperparathyroidism, along with other factors.3 Elevated Ca concentrations suppress PTH production, thus reducing concomitant skeletal Ca loss, in the presence of rapid mobilization. Hypercalemia targets the kidneys to excrete excess Ca into the urine to prevent toxic levels in the serum. Treatment is aimed at the underlying cause of the increased bone mobilization of Ca stores. In addition to this, after symptoms develop (see Tables 3 and 4) or serum Ca levels exceed 12 mg/dL, acute treatments are needed concomitantly (see Table 5). These treatments include dietary restriction, fluid resuscitation, and a reduction of Ca-containing medications. In the case of severe hypercalcemia (>15 mg/dL) rapidly infused NS increases renal excretion of Ca. This, followed by administration of diuretics, can assist in normalizing serum Ca levels.6 Dialysis may be required if the serum Ca levels do not respond to the NS infusion to prevent calcifications.

Ca
Ca is found mainly in bones and teeth. It is an extracellular cation responsible for many physiological functions, such as bone metabolism and neuromuscular function, due to the protein-binding capacity of Ca. The intestine, kidneys, and bones work synergistically to regulate Ca balance in response to PTH levels and vitamin D status. Vitamin D and PTH work in concert to maintain Ca homeostasis. Ca levels target the parathyroid gland to either increase or decrease production of PTH, which in turn drives intestinal absorption of Ca, renal absorption/ excretion of phosphorus (P) and Ca, and bone mobilization of Ca.30 PTH also converts the inactive form of vitamin D to its active form (1,25-dihydroxyvitamin D; calcitriol), to enhance Ca absorption in the GI tract.30 This functionality is decreased in the setting of vitamin D deficiency. Together, PTH and calcitriol activity targets the proximal renal tubular cells to increase and/or decrease Ca and P reabsorption.1,30 They are also responsible for regulating the release of skeletal Ca into the ECF, in an effort to augment the consequences of hypocalcemia.1 The assessment of Ca status must include an evaluation of P and Mg status, in addition to PTH and vitamin D status. Serum P and Ca have a reciprocal relationship, whereby when one goes up the other comes down.3 Clinically, in cases of rapid correction of hypophosphatemia, the increased rate of Ca entering the cell can lead to life-threatening hypocalcemia. Because of this relationship, Ca and P levels need to be assessed prior to establishing a treatment plan. Furthermore, hypomagnesemia is associated with hypocalcemia, which is likely related to an inhibition of PTH in the setting of suboptimal Mg levels.29 With concomitant hypomagnesemia and hypocalcemia, Mg must be corrected prior to achievement of a normalized Ca level. The DRI of Mg for adults >18 years of age is 1,000 1,200 mg/d28 and is approximated to be 1015 mEq/d6 for

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P
P is the primary intracellular anion responsible for cellular and bone structure, storage and transfer of energy in the form of adenosine-triphosphate, and is an acid-base buffer. Although P imbalances can occur in light of many clinical scenarios, imbalances are typically a result of altered intestinal absorption, renal insufficiency, bone resorption/deposition, or cellular redistribution and are highly regulated by endocrine function. Intestinal absorption of P is dependent on serum P levels and vitamin D status. The intestine can absorb up to 80% of dietary intake in the presence of hypophosphatemia and/or elevated PTH. Within the kidney, the glomerulus regulates P absorption in response to PTH, acid-base imbalance, and volume expansion.1 Hyperparathyroidism is the main contributor to increased urinary P loss and to mobilization of P from the Ca-P pool, within the bone matrix. Lastly, intracellular shifts can lead to P imbalance. Anabolism, acid-base imbalances, and hormone secretions lead to intracellular shifts depleting serum P. In clinical practice, this is most often seen when a high carbohydrate load is administered, thus providing PN with inadequate P content, and/or in cases of refeeding syndrome. In refeeding syndrome, hypophosphatemia results because of the increased requirement for the phosphorylation of glucose.18-20 The assessment of P status should include an evaluation of Ca, PTH, and vitamin D status. As discussed earlier, serum Ca and P have a reciprocal relationship, in which an excess of one results in a depletion of the other.3 It is also clear that hypoparathyroidism leads to increased renal absorption of P, whereas vitamin D deficiency leads to decreased GI absorption.1 All 3 components are vital to the overall assessment of P status. The DRI for adults >18 years of age is 700 mg/d and is approximated to be 2040 mmol/d6 for PN-dependent individuals, with adjustments as needed. Dietary P absorption is reduced significantly in the presence of vitamin D deficiency and with the use of P-binding antacids. Whether supplemented by mouth or IV, absorption depends on adequate GI and renal function. Hypophosphatemia. Hypophosphatemia is defined as a serum P level <2.7 mg/dL. Although serum P levels may be depressed (below reference range), this is not a reflection of intracellular or total body stores of P. Since P shifts between the intracellular and extracellular compartments, assessment must include all parameters outlined above to determine a treatment plan. Asymptomatic mild hypophosphatemia (2.32.7 mg/ dL) can be treated with oral supplementation and increased dietary intake, in most cases (see Tables 35). Symptomatic patients with hypophosphatemia and/or moderate to severe depletion (1.52.2 mg/dL and <1.5 mg/dL, respectively)

will require IV supplementation, as will also the patient with intestinal failure6,25,33 (see Tables 35). P supplementation can be given orally or by IV and delivered as K or Na. Potassium phosphate should be avoided when P levels exceed 4 mmol/L, to reduce the development of hyperkalemia.6,17,25 If IV supplementation is indicated, infusions should be over the course of 6 hours or more to prevent rapid correction leading to rebound hypocalcemia (see Table 5). Hyperphosphatemia. Hyperphosphatemia is defined by an elevation in serum P to >4.5 mg/dL. As with hypophosphatemia, elevated P levels do not reflect total body stores. Assessment of P status requires an evaluation of intestinal absorption, renal function, bone absorption/ deposition, and cellular redistribution to develop a thorough treatment plan. Treatment of asymptomatic hyperphosphatemia starts with reducing the amount of P ingested and/or the use of phosphate binders (see Tables 35). Phosphate binders, such as aluminum-containing antacids, must be monitored closely because of the potential for aluminum toxicity. Symptomatic patients with hyperphosphatemia may require volume resuscitation or dialysis in the setting of dehydration and renal insufficiency. When the Ca-P product exceeds 55 mg2/dL,33 there is a risk of forming salt precipitants leading to soft-tissue calcifications. In these cases, dialysis is also required to prevent vascular calcifications.

Chloride and Bicarbonate

Chloride (Cl) and bicarbonate (HCO3) are anions found primarily in the ECF and used to regulate acid-base balance and osmotic pressure. Carbon dioxide (CO2) is regulated by the lungs, and HCO3 (often reported as CO2) is regulated by the kidneys. The pulmonary and renal systems maintain serum pH by adjusting excretion as deviations in pH occur. The kidneys are the primary regulatory mechanism for maintaining HCO3 and Cl levels, with the proximal renal tubules being the site of reabsorption and excretion.3 Serum CO2 and Cl abnormalities develop during acid-base imbalances, in which the pulmonary and renal systems attempt to compensate for pH shifts in an effort to regain homeostasis. CO2 is a weak acid excreted by the lungs. As the serum pH changes, the lungs adjust alveolar ventilation in an effort to retain or excrete CO2, while the kidneys retain or excrete hydrogen and HCO3. Serum CO2 is typically elevated during alkalosis and depressed during acidosis, while Cl levels typically respond in the opposite direction as CO2. Adequate intake of Cl for PN-dependent individuals is 2 g/d and approximately 12 mEq/kg of body weight,

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684 Journal of Parenteral and Enteral Nutrition / Vol. 35, No. 6, November 2011

with adjustments made as needed. In PN, CO2 levels are driven by the acetate dose, which varies based on the acid-base balance. Absorption occurs in the small intestine, as both Cl and HCO3 tend to follow Na for absorption.34 Although colonocytes have the ability to absorb small amounts of Cl and HCO3, this is likely more pronounced in malabsorption syndromes, where the colon compensates for decreased intestinal absorption.35,36 CO2 is a measure of total HCO3 in all the chemical forms (dissolved CO2, carbonic acid, and bicarbonate). Since carbonic acid and dissolved CO2 are negligible, serum CO2 is an acceptable measure for assessing HCO3. Because Cl and HCO3 are both anions in the ECF, they are inversely related in that as one increases the other must decrease.3 This functionality is essential to maintaining osmotic pressure. During an acid-base imbalance, serum CO2 greatly affects K balance, as K and CO2 also are inversely related. An example of this is seen during metabolic acidosis, where an elevated serum CO2 correlates with hypokalemia. The opposite is true of a metabolic alkalosis. Because of the interrelationships between these electrolytes, a thorough assessment includes evaluation of CO2, Cl, and K. When treating electrolyte abnormalities and/or providing IV hydration, assessing Cl and CO2 levels is imperative for selecting the appropriate therapy. Medications can worsen imbalances, as diuretics and H2 blockers contribute to Cl wasting and antacids contain bicarbonate.6 With all Cl and CO2 imbalances, the workup should include the assessment of medications. The first step is treating the underlying condition, followed by assessing all exogenous sources of Cl or bicarbonate. IV medications, IV hydration, and PN solutions often contain Cl and/or bicarbonate, which can lead to an imbalance over time. Maintenance fluids for hyperchloridemia and/or depressed serum CO2 should be NS, Lactated Ringers, and/or dextrose in 5% water to improve the ratio of Cl:CO2 in the ECF (see Table 2). Hypochloridemia and/ or elevated serum CO2 levels respond best to NS, to improve the ratio of Cl:CO2. For PN-dependant patients, an adjustment of the Cl and/or acetate content is needed in the presence of abnormalities.

parameters. One guideline will not fit every case, and therefore a multispecialty milieu will enhance clinical judgment and promote education, both critical components of optimal patient outcome and clinician growth.

Glossary
1. Osmolarity (lab calculated)*: number of solutes in 1 L of solution (mOsm/L) 2. Osmolality (measured)*: concentration of body fluids (ratio of solutes to water); the ability to create oncotic pressure (mOsm/kg) 3. Bone resorption: the process by which osteoclasts break down bone and release the minerals (mainly calcium), resulting in a transfer of calcium from bone to the blood 4. Tonicity: effective serum osmolarity; measure of solutes that cause a shift of water from one compartment to another 5. Isotonic: same tonicity as body fluids (280300 mOsm/kg), example: 0.9% sodium chloride solution 6. Hypotonic: tonicity < body fluids, example: 0.45% sodium chloride solution 7. Hypertonic: tonicity > body fluids, example: 3% sodium chloride solution 8. Reabsorption: absorption of already absorbed particles, usually referring to the kidneys 9. Refeeding syndrome: elicited response after feeding a severely malnourished catabolic patient; characterized by electrolyte abnormalities (ie, hypokalemia, hypomagnesemia, hypophosphatemia); retention of Na and water and possible depletion of thiamine 10. Hypovolemia: extracellular fluid deficit 11. Hypervolemia: extracellular fluid excess *Differences between osmolality and osmolarity are quite small, and the terms are often used interchangeably.

References
1. Doherty GM. Fluid and electrolyte management. In: Current Diagnosis & Treatment: Surgery. 13th ed. New York, NY: McGrawHill; 2010. http://www.accesssurgery.com/content.aspx?aid=5212 348. Accessed July 1, 2011. 2. Whitmire SJ. Nutrition-focused evaluation and management of dysnatremias. Nutr Clin Pract. 2008;23(2):108-121. 3. Heitz U, Horne M, Spahn D. Pocket Guide to Fluid, Electrolyte, and Acid-Base Balance, Mosbys 5th Edition. St Louis, MO: Elsevier; 2005. 4. Gomella LG, Haist SA. Fluids and electrolytes. In: Clinicians Pocket Reference. 11th ed. New York, NY: McGraw-Hill; 2007. http://www.accessmedicine.com/content.aspx?aID=2701183. Accessed July 1, 2011. 5. Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493-1499. 6. Langley G. Fluid, electrolytes, and acid-base disorders. In: Gottschlich M, DeLegge MH, Mattox T, eds. The A.S.P.E.N.

Conclusion
The intricacy of fluid and electrolyte management in patients with complex intestinal failure can be challenging and the treatment multifactorial. Severe abnormalities can be life threatening if the appropriate management is not promptly instituted. Assessment involves a thorough review of the underlying disease process, fluid status, absorptive capacity of the GI tract, and renal function, as treatment plans are adapted in response to these

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Nutrition Support Core Curriculum: A Case-Based ApproachThe Adult Patient. Silver Spring, MD: American Society of Parenteral and Enteral Nutrition; 2007:104-128. 7. Kraft M, Btaiche I, Sacks G, Kudsk K. Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm. 2005;63:1663-1681. 8. Kroll MH, Elin RJ. Relationships between magnesium and protein concentrations in serum. Clin Chem. 1985;31(2):244-246. 9. Saladin KS. Anatomy & Physiology: The Unity of Form and Function. 2nd ed. Boston, MA: McGraw-Hill; 2001. 10. Pemberton LB, Pemberton DK, Cuddy PG, eds. Treatment of Water, Eelectrolyte, and Acid-Base Disorders in the Surgical Patient. New York, NY: McGraw-Hill; 1994. 11. McGee S, Abernethy W, Simel D. Is this patient hypovolemic? J Am Med Assoc. 1999;281:1022-1029 12. Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064-2072. 13. Kapoor M, Chan GZ. Fluid and electrolyte abnormalities. Crit Care Clin. 2001;17(3):503-523. 14. Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581-1589. 15. Quamme GA, Dirks JH. Magnesium metabolism. In: Narins RG, ed. Maxwell and Kleemans Clinical Disorders of Fluid and Electrolyte Metabolism. 5th ed. New York, NY: McGraw-Hill; 1994. 16. Verbalis J, Goldsmith S, Greenberg A, Schrier R, Sterns R. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120:S1-S21. 17. Sedlacek M, Schoolwerth A, Remillard B. Electrolyte disturbances in the intensive care unit. Semin Dial. 2006;19(6):496-501. 18. Byrnes M, Stangenes J. Refeeding in the ICU: an adult and pediatric problem. Curr Opin Clin Nutr Metab Care. 2011;14:186-192. 19. Stanga Z, Brunner A, Leuenberger M, et al. Nutrition in clinical practicethe refeeding syndrome: illustrative cases and guidelines for prevention and treatment. Eur J Clin Nutr. 2008;62:687-694. 20. Khan LUR, Ahmed J, Khan S, MacFie J. Refeeding syndrome: a literature review. Gastroenterol Res Pract. 2011. Article ID 410971. 21. Agarwal R, Afzalpurkar R, Fordtran JS. Pathophysiology of potassium absorption and secretion by the human intestine. Gastroenterology. 1994;107(2):548-571. 22. Clausen T, Everts M. Regulation of the Na, K-pump in skeletal muscle. Kidney Int. 1989;35:1-13. 23. Brown KA, Dickerson RN, Morgan LM, Alexander KH, Minard G, Brown RO. A new graduated dosing regimen for phosphorus replacement in patients receiving nutrition support. J Parenter Enteral Nutr. 2006;30:209-214. 24. Geerse DA, Bindels AJ, Kuiper MA, Roos AN, Spronk PE, Schultz MJ. Treatment of hypophosphatemia in the intensive care unit: a review. Crit Care. 2010;14:R147. 25. Hemstreet BA, Stolpman N, Badesch DB, May SK, McCollum M. Potassium and phosphorus repletion in hospitalized patients: implications for clinical practice and the potential use of healthcare information technology to improve prescribing and patient safety. Curr Med Res Opin. 2006;22(12):2449-2455. 26. Sevastos N, Theodossiades G, Archimandritis A. Pseudohyperkalemia in serum: a new insight into an old phenomenon. Clin Med Res. 2008;6(1):30-32. 27. Tong MG, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med. 2005;20(1):3-17. 28. National Academies Press. http://www.nap.edu. Accessed July 16, 2011. 29. Wilson R, Erskine C, Crowe P. Hypomagnesemia and hypocalcemia after thyroidectomy: prospective study. World J Surg. 2000;24:722-726. 30. Brown EM, Herbert SC. Calcium-receptor-regulated parathyroid and renal function. Bone. 1997;20:303. 31. Itoh R, Suyama Y. Induction plasma sprayed biological-like apatite coatings for biomedical applications. Am J Clin Nutr. 1996;63:735740. 32. Heaney RP. Protein intake and the calcium economy. J Am Diet Assoc. 1993;93:1259-1260. 33. Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J Kidney Dis. 2000;35(6):1226-1237. 34. Turnberg LA, Fordtran JS, Carter NW, Rector FC Jr. Mechanism of bicarbonate absorption and its relationship to sodium transport in the human jejunum. J. Clin Invest. 1970;49:548-556. 35. Jeejeeboy K. Short bowel syndrome: a nutritional and medical approach. CMAJ. 2002;10(166):1297-1302. 36. Vogt J, Wolever T. Fecal acetate is inversely related to acetate absorption from the human rectum and distal colon. J Nutr. 2003;3145-3148.

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