Hyperkalemia & Hypokalemia
Glen E. Hastings MD April 27, 1999 I. Physiology: A.. Potassium’s Role in Cellular Function : + The normal plasma K range is 3.5-5.0 mEq/L. The normal intracellular range is150 mEq/L. The extracellular to intracellular ratio of 36:1 to 37.5:1 is maintained by a cell-membrane-bound + Na+/K+/ATPase pump, which uses energy from ATP to repetitiously extrude 3 Na ions in exchange for + 2 K ions. This creates a negative (-75mV) charge across the resting membranes of the cells of the + + body. Outward diffusion of K ions through selective K channels increases the negative electrical potential further until at about –90mV the membrane depolarizes. This process drives nerve & muscle conduction, hormone release, protein synthesis, embryogenesis, and many other bodily processes. + Hence the first symptoms of K abnormalities are frequently muscle weakness or cardiac dysrhythmias. Regulation of Potassium : + Ingested K is initially buffered intracellularly. Insulin, catecholamine levels & extracellular + + pH influence cellular uptake & therefore determine extracellular K levels. The major mode of K + regulation is through K excretion by the principal cells of the cortical collecting duct of the kidney. + + Na /K /ATPase pump structures are imbedded in the principle cell’s basement membrane adjacent to + + the peritubular capillary. On the luminal surface of the principal cell are K conductance channels, Na + + + conductance channels, a Na /H ion exchanger, & a K /Cl cotransporter. Potassium exits the luminal + + surface because of a favorable concentration gradient, powered by the inward Na flow through the Na + + conductance channels, attracted by the Na /K /ATPase pump. Potassium secretion is thus dependent + + upon the availability of luminal Na , low urinary K concentrations & low urine osmolality. It is therefore + + related to luminal flow rates & to GFR. Anything that influences the Na /K /ATPase pump (e.g. + + aldosterone), the Na conductance channels (e.g. triamterine, & amiloride), the K conductance + channels (opened by aldosterone signaling) or the K /Cl cotransporter (e.g. luminal Cl concentration) + will effect K excretion. The Influence of the GI Tract in Potassium Balance : In a normal person, 92% of the potassium ingested is excreted by the kidney; 8% by the GI tract. GI excretion may increase to 30% in CRF. It may also increase dramatically with diarrhea (Table 2). The Transtubular Potassium Gradient (TTKG): The TTKG measures the gradient across the cellular membrane of the principal cells in the cortical collecting duct. In hypokalemia a TTKG <2 means that the cause is non-renal. In a hyperkalemic patient, a TTKG >10 means that the cause is non-renal. The formula for TTKG:
+ 1 1,2,3 1,2,3
TTKG = K
OsmUrine ÷ OsmPlasma + K Plasma
Hyperkalemia: 1,2 Definitions : + Hyperkalemia is defined as any plasma K level greater than 5.0mEq/dL. + Severe hypokalemia requiring urgent treatment & EKG monitoring is when K levels > 6.0mEq/dL. Potentially life threatening levels are > 6.5mEq/dL. Symptoms & Signs : Musculoskeletal weakness is typically the earliest symptom of hyperkalemia. Since hyperkalemia lowers the depolarization threshold, part of the muscle tissue remains partially depolarized. Although this can lead to muscle paralysis, serious cardiac dysrhythmias usually supervene before this occurs. Sustained partial depolarization progressively flattens the P wave of the EKG & widens the QRS complex. Ventricular repolarization however, is enhanced, so the T waves become peaked. With progression these changes merge to form a “sign wave” pattern. Unfortunately, EKG changes are not sensitive indicators of the danger of asystole, or ventricular fibrillation, so treatment decisions should be + based on laboratory determined measurements of plasma K .
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Causes of Apparent Hyperkalemia
Pseudohyperkalemial : Laboratory Error, Hemolysis & K Leak: Mechanical trauma, clenching & unclenching of the hand, & allowing unspun blood samples to sit are all + causes of hemolysis. These as well as simple laboratory error cause falsely elevated K levels. Pseudohyperkalemia may also occur with marked thrombocytosis (>400,000), or leukocytosis (100,000). It is first necessary to exclude these possibilities before proceeding with treatment. Causes of True Hyperkalemia: Hyperkalemia is the result of an increase in K intake, a decrease in K excretion or a shift of potassium from the intracellular to the extracellular compartment.
True Hyperkalemia: Drugs: Excluding patients with frank renal failure, most cases of hyperkalemia are of multifactorial origin, not infrequently involving a prescription drug, coupled with age or disease related impairment of GFR, Renal + excretion of K is decreased when GFR<25% of normal). A list if drugs most frequently implicated along with their modes of action is shown as Table 1.
Table 1: K Altering Drugs & Their Mechanisms of Action Type of Drug Diet & Dietary Supplement Drug Potassium Supplements Salt Substitutes Spironolactone Amiloride Triamterine ACE Inhibitors AT II Receptor Blockers NSAIDS β -Blocking Agents α-Adrenergic Agonists Trimethoprim Potassium Penicillin G Pentamidine Cyclosporine T acrolimus Succinylcholine Digoxin Heparin ↑ Exogenous K + ↑ Exogenous K
+ + 2,4
Mechanism of Action
K Sparing Diuretics
Aldosterone Antagonism + Na channel blockade in principal cells + Na channel blockade in principal cells ↓ Aldosterone, RBF & GFR. ↓ Aldosterone, RBF & GFR. ↓ Renin, Aldosterone, RBF & GFR. Impaired Cellular Glucose Uptake Impaired Cellular Glucose Uptake Na channel blockade in principal cells + ↑ Exogenous K + Na channel blockade in principal cells ↓ Aldosterone Release, & ↓ Na / K ATPase Activity + + ↓ Aldosterone Release, & ↓ Na / K ATPase Activity
+ + +
Angiotensin II Blockers Antiinflammatories Adrenergic Drugs
Immune Modulating Drugs
K channel blockade in principal cells + + ↓ Na / K ATPase Activity ↓ Aldosterone Synthesis
True Hyperkalemia Secondary to Decreased Excretion : Prerenal Azotemia: In congestive heart failure, liver failure with ascites, & chronic renal disease with volume depletion, a state of “ineffective circulating blood volume” occurs where insufficient Na is delivered to the cortical + collecting duct for K secretion to occur. Hyperkalemia is likely when urine output < 600cc/day. True Hyperkalemia Secondary to Decreased Excretion : Kidney Failure: Hyperkalemia does not occur in chronic renal failure until the GFR is < 10cc/minute, or in patients with hypoaldosteronism or aldosterone resistance. It is common in acute renal failure caused by acute + tubular necrosis because of concomitant metabolic acidosis & K release secondary to hemolysis or tissue necrosis. Acute glomerulonephritis, sickle cell disease, interstitial nephritis, systemic lupus erythematosus, amyloidosis, lead nephropathy, obstructive uropathy with associated type 4 RTA, postrenal transplantation & pseudohypoaldosteronism may all produce hyperkalemia. True Hyperkalemia Secondary to Decreased Excretion : Hyporeninemic Hypoaldosteronism: After drugs & kidney failure, the third most common cause of hypokalemia is hyporeninemic hypoaldosteronism, a condition usually occurring in diabetic patients or those with chronic interstitial nephritis & mild to moderate renal failure (GFR ± 20 60cc/minute). The condition is confirmed by the
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presence of (usually asymptomatic) hyperkalemia, an inappropriately low urinary K , a transtubular K gradient (TTKG) < 5 & a low aldosterone level. Prescription of an NSAID to such a patient may + precipitate life threatening hyperkalemia. The condition is treated with low K diet & loop or thiazide diuretics combined with NaHCO3. Refractory cases may require fludrocortisone or Kayexalate •
1 + +
True Hyperkalemia Secondary to Decreased Excretion : Adrenal Insufficiency or Resistance: Autoimmune disease & HIV have supplanted tuberculosis & primary atrophy as causes of Addison’s disease. The most common form of congenital adrenal hyperplasia is 21-hydroxylase deficiency which impairs glucocorticoid and mineralocorticoid synthesis which stimulating ACTH producing virilization, salt wasting & hyperkalemia during infancy. It is treated with steroid replacement. Generalized Pseudohypoaldosteronism results from a congenital diminution of aldosterone receptors. The acquired form occurs as a result of tubulointerstitial dysfunction in such conditions as amyloidosis, chronic pyelonephritis, or obstructive uropathy. Both feature salt wasting, hypovolemia, & hyperkalemia but differ from adrenal insufficiency in that both renin & aldosterone are increased. True Hyperkalemia 2 to Decreased K Excretion : Distal Hyperkalemic Renal Tubular Acidosis: + + In distal hyperkalemic (Type 4) RTA K & H ion excretion are both impaired producing a hyperchloremic acidosis with hyperkalemia. The most common intermediate causes are insufficient aldosterone production or aldosterone resistance. Obstructive uropathy & sickle cell disease are common causes. Management is as with hyporeninemic hypoaldosteronism. True Hyperkalemia 2 to Decreased K Excretion : Selective Renal Tubular Defects: Gordon’s syndrome features hyperkalemia, & volume expansion with related hypertension, in patients with normal renal function. It results from a selective increase in the tubular reabsorption of Cl which expands circulating volume depressing renin & aldosterone. Treatment with thiazides. Selective defects in K are seen in cyclosporine nephropathy, & lupus nephritis. True Hyperkalemia 2 to Increased K Intake or Release : Tissue Injury & Hemolysis: Rapid tumor lysis during chemotherapy, rapidly progressing hemolytic anemias, crush injuries, rhabdomyolysis secondary to heat injury, neuroleptic malignant syndrome, or drugs, transfusion reactions or stored blood administration may produce hyperkalemia. Vigorous physical exercise alone may cause hyperkalemia as do the drugs & supplements in Table 1. True Hyperkalemia 2 to Intracellular/Extracellular K Shifts : Metabolic Acidosis & Hypertonicity: + Respiratory acidosis does not produce hyperkalemia because the excessive H ions and their accompanying anions are distributed to both the intracellular & extracellular compartments & do not therefore cause a K shift. Metabolic acidosis caused by inorganic acids and conditions like diabetic ketoacidosis featuring hypertonicity are frequent causes of hyperkalemia, best treated by remedying the precipitating condition. Hyperkalemia 2 to Intracellular/Extracellular K Shifts : Familial Hyperkalemic Periodic Paralysis: Familial hyperkalemic periodic paralysis is an autosomal dominant inherited condition, caused by dysfunction of the sodium channels of the muscles of the limbs resulting in periodic episodes of + weakness accompanied by mild hyperkalemia which may be precipitated by cold, exercise, or K loading. It may be diagnosed by family history & treated with a high CHO diet. Acetazolamide; & albuterol may be used during acute attacks. Diagnosis: A history of drugs and medications, family history, dietary habits and concomitant illnesses is essential. Physical exam should focus upon the blood pressure, postural change in blood pressure & pulse, & signs of congestive heart failure, liver failure with ascites, or acute or chronic renal disease. Initial laboratory values should include serum & urine electrolytes & osmolality, BUN & creatinine, arterial blood gasses, routine urine analysis, liver profile, & EKG. Renin & aldosterone levels, cosyntropin stimulation, echocardiography, & chest x-ray may also be useful in specific cases..
1,2,3 o + 1 o + 1 o + 1 o + 1 o + 1
E. • • •
F.Emergency Treatment of Acute Hyperkalemia
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Correction of plasma K levels above 6.0-6.5 mEq/dL or with EKG changes should generally by performed under continuous EKG monitoring. In previous years NaHCO3was included in most protocols for treatment of hyperkalemia. Recent experience however has shown NaHCO3 to be unreliable unless the underlying problem is metabolic acidosis caused by an inorganic agent. The agents of choice & 1,2,3 dosages are shown in Table 2 below:
Therapy & Mechanism of Action Antagonism of membrane effects of hyperkalemia Calcium Gluconate (10%) Stimulation of potassium uptake into cells Glucose and insulin Dosage Onset Duration of Effect 60 minutes
10-30 mL, IV
< 5 minutes
10-20U regular insulin with 30-50 grams glucose over 15-30 minutes 10-20mg 40 mg, IV 20-40 g rectally or orally with sorbitol N/A
Inhaled Albuterol Removal of potassium from the body Diuretics (furosemide) Cation-exchange resin Peritoneal dialysis or hemodialysis
30 minutes Starts with diuresis 60 minutes 120 minutes A few minutes
2 hours Variable 6 hours Variable
Definitions 2 Mild Hypokalemia: 3.0-3.5 mEq/L=Total body deficit =150-300 mEq/1.75m 2 Moderate Hypokalemia: 2.5-3.5 mEq/L=Total body deficit =300-500 mEq/1.75m 2 Severe Hypokalemia: <2.5 mEq/L=Total body deficit =>500 mEq/1.75m Symptoms of Hypokalemia : Mild hypokalemia is most often asymptomatic. As plasma levels drop below 3.0mEq/dL nonspecific symptoms like weakness, malaise & constipation appear. At levels less than 2.5mEq/dL, hypotension & rhabdomyolysis secondary to decreased glycogen synthesis may occur. Below 2.0mEq/dL interstitial nephritis or an ascending paralysis may appear. Hypokalemia & cardiac arrhythmias increase, especially in the presence of ischemia, hypertension or digitalis therapy.
C.Causes of Hypokalemia : The most common cause of hypokalemia is excessive renal loss or an intracellular shift of extracellular + potassium induced by prescription drugs. Less frequently hypokalemia results from a shift of K into the intracellular compartment induced by metabolic alkalosis, from inadequate potassium intake, from excessive loss in diarrheic stool, or from another cause of renal wasting.
Hypokalemia Secondary to Drugs : Drugs may precipitate hypokalemia in one of three ways: by causing an intracellular shift of potassium, by accelerating renal loss, or by causing diarrhea. Drugs commonly causing hypokalemia are listed in Table 3:
Table 3: Drugs Causing Hypokalemia & Their Mechanisms of Action Drugs Causing Intracellular K Shift β Adrenergic Agonists Epinephrine Decongestants Bronchodilators Tocolytic Drugs
+ 5 +
Drugs that ↑ Renal K Loss
Drugs that ↑ Fecal K Loss Phenolphthalein Na Polystyrene Sulfonate
Diuretics: Thiazides Loop Diuretics Steroids & Steroid-like Drugs Fludrocortisone
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Xanthine Derivatives Theophylline Caffeine Overdose Related Hypokalemics Insulin Verapamil Chloroquine Barium Toluene
Hi dose glucocorticoids Licorice Gossypol (an herbal remedy) High dose Penicillins o + Magnesium Depleting Drugs with 2 ↓ K : Cisplatin Foscarnet Amphotericin D Aminoglycosides
Hypokalemia Secondary to Inadequate Intake or Malabsorption of K : Especially likely to develop hypokalemia along with potentially life threatening hypophosphatemia are patients with anorexia nervosa, or other starvation syndromes, chronic binge alcoholics who do not eat during binges, and persons who practice geophagia. Geophagia, the ingestion of clay from the soil + binds K in the gut & prevents absorption, Hypokalemia Secondary to Gastrointestinal Loss of K : In addition to the bowel stimulating drugs shown in Table 3, vomiting, acute or chronic secretory O diarrhea, or congenital diarrhea, may cause hypokalemia. Vomiting induces metabolic alkalosis 2 to + O + Cl loss. Renal K wasting 2 to ↑ HCO3 loss ensues. Table 4 lists other sources of g. i. K loss:
Table 4: Causes of Gastrointestinal K Loss Infectious Diarrhea Cholera Salmonella Strongyloides Yersinia AIDS related diarrhea Tumors VIPoma Villous Adenoma of Colon Zollinger-Ellison Syndrome
Cancer Therapy Chemotherapy Radiation Enteropathy Jejunoileal bypass Enteric Fistula Malabsorption Syndromes Congenital Chloride Diarrhea Vomiting & Nasogastric tube drainage: Cause loss of chloride & metabolic alkalosis + producing renal K loss.
Hypokalemia Secondary to Increased Intracellular uptake of K : Two common conditions featuring hypokalemia 2 to intracellular shifts are during the correction of DKA, & in delirium tremens. In DKA the shift is induced by insulin. In DT’s by epinephrine. Severe + hypothermia may produce an intracellular K shift with significant hypokalemia. Hyperthyroidism presents in Asian & Hispanic men with hypokalemia & weakness about 9% of the time. Increased blood cell production in hypermetabolic states such as acute myelogenous leukemia, or newly treated megaloblastic anemia is another. Familial Hypokalemic Periodic Paralysis is an inherited disorder of the muscle cell calcium channels causing hypokalemia & profound (usually distal) muscular weakness. Onset is before age 25. Attacks usually occur at rest & may be precipitated by carbohydrate loading. Treatment is with acetazolamide & low carbohydrate diet. + 1,3,5 Hypokalemia Secondary to Accelerated Renal K Loss Related to Renal Tubular Defects : + o The most frequent cause of excess renal K loss is metabolic alkalosis following Cl loss 2 to vomiting. o Less frequent causes include the metabolic alkaloses 2 to various endocrinopathies which will be described in the next section and the renal tubular defects discussed below: + Renal tubular acidosis (RTA): In RTA Type I (Classic distal RTA) distal H secretion is impaired, + + increasing Na reabsorption & K excretion. Acidification of the urine usually controls the + hypokalemia. In proximal (Type II) RTA, increased HCO3 & Na are delivered to the distal renal + tubule causing hypokalemia. Treatment requires both HCO3 & K supplementation. Liddle's syndrome is a rare autosomal dominant condition in which enhanced sodium channel + activity increases distal Na resorption & thereby produces hypokalemia & hypervolemia related hypertension. Amiloride or triamterine but not spironolactone are effective treatments. The Syndrome of Apparent Mineralocorticoid Excess results from an impairment of cortisol metabolism in the cortical collecting ducts which produces manifestations similar to Liddle’s Syndrome. The difference is that exogenous corticosteroids correct the defect. Amiloride, or spironolactone & Na restricted diet will correct the hypokalemia. Bartter's syndrome is an autosomal recessive condition which usually presents in childhood as
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growth retardation, hypokalemia, metabolic alkalosis, hyperaldosteronism & hyperreninemia. The + defect is increased Na resorption in the thick ascending loop of Henle. Management includes K & Mg replacement, NSAIDS, & amiloride or triamterine. Gitelman’s Syndrome is also called the syndrome of hypomagnesemia-hypokalemia with hypocalciuria. It is caused by an abnormality in the NaCl cotransporter in the distal convoluted tubule. Its effects are milder than in Bartter’s Syndrome & may present in adults
Hypokalemia Secondary to Accelerated K Loss Secondary to Endocrinopathies : o Less frequent causes of hypokalemia include the metabolic alkaloses 2 to various endocrinopathies: Primary Hyperaldosteronism (Conn’s Syndrome), 60% of which is caused by an secreting adenoma of the adrenal cortex, & 40% by hyperplasia, presents with hypertension, & hypokalemia. Adenomas are treated surgically while hyperplasia is managed with amiloride, spironolactone, ACE inhibitors, or calcium channel blockers. Glucocorticoid Remediable Hyperaldosteronism is a rare autosomal dominant disorder occurring before age 21, in which aldosterone production occurs in the wrong layer of the adrenal cortex making it subject to over-stimulation by ACTH. Its management involves administering glucocorticoids which suppress ACTH production. Congenital Adrenal Hyperplasia may be caused by one of two inherited enzyme deficiencies. 11β-hydroxylase deficiency causes hypertension, hypokalemia, & virilization. 17-hydroxylase deficiency causes only hypertension & hypokalemia but not virilization. Both occur in childhood. Cushing’s Syndrome whether of adrenal or pituitary origin may cause hypokalemia & metabolic alkalosis. Treatment depends upon the cause. Hyperthyroidism may present with hypokalemia & weakness in 2% to 8% of Asian & Hispanic + men. It responds to exogenous K , but may cause rebound hyperkalemia. Hypokalemia may occur episodically & be thereby confused with familial hypokalemic periodic paralysis. Diagnosis of Hypokalemia There are many diagnostic decision trees for hyponatremia. The one selected & shown on the next page is based employs readily available clinical information. It excludes hyponatremia secondary to acute conditions such as acute tubular necrosis, & the metabolic acidoses associated with ethylene glycol or methanol ingestion. It also excludes hyperthyroidism familial hypokalemic periodic paralysis & other conditions causing transient intracellular shifts of potassium.
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Chronic Hypokalemia Exclude Pseudohypokalemia Exclude Drugs
↓ or Normal Blood Pressure
↑ Blood Pressure
Urine K <25mMol/L
Urine K >25mMol/L
↑ Renin: • Malignant HBP • Renin secreting tumor ↑ HCO 3 : • Vomiting or NG loss • Current Diuretic Use • Bartter’s Syndrome • Gitleman’s Syndrome • Cl Losing Diarrhea or other Cl depletion. • Post Hypercapnia
↓ Renin :
↓ or Normal HCO 3 : • HCO3 losing Diarrhea + • ↓ K Intake
↑ HCO 3 : • Previous use of diuretics.
↓ HCO 3 : • RTA I or II • DKA • Delerium Tremins.
↑ Aldosterone: o •1 Hyperaldosteronism • Glucocorticoid Responsive Hypoaldosteronism
↓ Aldosterone: • Cushing’s • Liddle’s • Licorice
Treatment of Hypokalemia How Much Is the Deficit?: In general a reduction in K from 4mEq/dL to 3mEq/dL represents loss of 200 to 400mEq of total body potassium. This estimate does not include transcellular shifts. 1,5 Diet, Supplements & Salt Substitutes : As with many things on medical practice, the best way to treat hypokalemia is to prevent its occurrence in the first place, & the safest way to prevent its occurrence is through diet & oral + supplements. Table 5 is a list of foods high in K content.
Table 5: High K Foods Highest (>1000mg/100g): • Dried Figs • Molasses • Seaweed Very High (>500mg/100g): • Dried Fruits (Dates, Prunes) • Nuts • Avocados • Bran Cereals • Wheat Germ • Lima Beans
High Content (>250mg/100g): • Vegetables: Spinach Tomatoes Broccoli Winter Squash Beets Carrots Cauliflower Potatoes
High Content (>250mg/100g): • Fruits: Bananas Cantaloupe Kiwis Oranges Mangos • Meats: Beef & Veal Pork Lamb
Unfortunately dietary K alone will not correct the K depletion caused by diuretics because dietary K + is almost completely coupled with phosphates. The physiological basis for diuretic induced K depletion is metabolic alkalosis secondary to Cl depletion, so supplementation with KCl is also required, either in the form of supplements or “salt substitutes”. Unfortunately, these substances are the most frequent sources of inadvertent hyperkalemia. Salt substitutes are known to cause small bowel perforation in rare instances. This is least likely when micronized forms are used.
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Magnesium depletion will prevent effective K replacement, & may need to be replaced concomitantly. + Spironolactone mitigates both K & magnesium loss & may be more appropriate for those with cardiovascular risk factors. Spironolactone works by inhibiting the binding of spironolactone to its receptor, while both triamterine & amiloride are independent of aldosterone. +1,3 Intravenous K : Patients with cardiovascular emergencies secondary to hypokalemia related cardiac arrythmias should + be admitted to the CCU for K replacement under continuous EKG monitoring. KCl should Never be injected directly into the vein as the body has no mechanism for protecting itself from sudden surges of + K . In true emergency situations, infusion rates up to 20 or even 40mEq/hour for short periods of time may be used in order to terminate life-threatening arrhythmia. To achieve such flow rates 100 up to 400mEq of KCl might be mixed with 1000cc of saline. Thereafter the flow rate should be reduced to a more conventional rate. Under ordinary circumstances KCl concentrations should not exceed 60mEq in each 1000cc of IV fluid. Under ordinary circumstances KCl replacement rates should not exceed 20mEq/hour even with monitoring. As with oral supplementation, magnesium deficit may prevent K replacement & should be replaced concomitantly. In patients with metabolic alkalosis (as in diuretic or vomiting induced hypokalemia) there is a + simultaneous Cl deficit, so Cl must be replaced along with K . In the treatment of diabetic ketoacidosis there frequently develops a PO4 deficit, so correction with a combination of KCl & KPO4 may be warranted. In other forms of metabolic acidosis KHCO3 is the preferred replacement therapy because Cl is limited to the extracellular compartment, while HCO3.is + not. This means that the infused K will also remain longer in the extracellular compartment & 1 correction of the total body deficit will be delayed . IV. 1. References: Peterson LN, Levi M: Disorders of potassium metabolism, Chapter 5 in Schrier, RW (ed): Renal & Electrolyte Disorders, 5th Edition. Philadelphia, New York, Lippencott-Raven, 1997, pp 192-240.
2.Perazella MA, Mahnensmith RL. Hyperkalemia in the elderly J Gen Intern Med 1997;12:646-656. 3.Mandel AK. Hypokalemia & hyperkalemia. Med Clin N Amer 1997;81(3):611-639. 4.Greenberg A. Hyperkalemia: Treatment options. Semin in Nephrolol 1998;18(1):46-57. 5.Gennari FJ. Hypokalemia. N Engl J Med 1998;339(7):451-8. 6.Halperin ML, Kamil KS Potassium. Lancet 1998;352:135-40. 7.Levinsky NG: Fluids and Electrolytes, in Petersdorf RG, Adams RD, Braunwald E, Isselbacher KJ, Martin JB, Wilson JD (eds): Harrison's Principles of Internal Medicine (12 ed.). New York, McGraw-Hill Book Co, 1991, pp. 278-289.