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Potassium

Joel M. Topf, M.D.Attending NephrologistPBFluids.blogspot.com

248.470.8163

IntroductionPotassium: Cool electrolyte

Potassium is a favorite electrolyte of both medical students and renal physi-ologists. It is illustrative, important and relevant in ways that most other elec-trolytes are not. Potassium physiology is straight forward and logi-cal. It is the electrolyte that demonstrates much of the

elegance of renal physiology. Potassium follows logical and eas-ily visualized rules. In addition to being a great exercise in renal physiology it is an important ion with severe implica-tions from disregulation: How do cardiac surgeons stop the heart af-ter hooking a patient to a heart lung bypass machine? They inject it with potassium. The heart which has been beating since 14 days after conception is stopped deadby po-tassium.Lastly, potassium disregulation is common, so lessons learned can be used on a daily basis.

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Table of ContentsPotassium 4

Total body potassium 4Potassium handling in three steps 5

Potassium intake 5Cellular distribution 6Renal potassium handling 7Potassium handling at the CCD 8Regulation of potassium excretion 10

Hypokalemia 12Definition 12Etiologies 12Consequences of low potassium 14Treatment 17

Hyperkalemia 19Etiologies 19

Pseudohyperkalemia 22EKG Changes 22Treatment 24

Calcium 24Remove potassium from the body 25Stop oral intake 25Move extracellular potassium into the cells 26Remove the potassium from the body: 27

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PotassiumPotassium is the primary intracellular cation

Total body potassiumPotassium is the dominant in-tracellular cation and because the intracellular compartment is twice the size of the extra-cellular compartment it is the most common electrolyte in the body.The intracellular K concentra-tion runs from 120-153 mmol/LThe extracellular concentra-tion runs from 3.5-4.5 mmol/L.A typical 70 kg man has nearly 4000 mmol of K. Of that only 56 mmol are extracellular. Humans typically have only 2000 mmol of Na.Question: what sizes do potas-sium pills come in?what is the typical dose of IV po-tassium? How does that compare to the extracellular potassium con-tent?

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Potassium handling in three steps

Potassium is regulated at three fundamental steps in the body: intake, cellular distribution and renal excretion.

Potassium intakeDiets are relatively rich in potassium with the average American ingesting 40 mmol of potassium a day. Unfortunately the RDA for potassium is 90 mmol. The kidney is good at being very po-tassium avid and can reduce potassium losses to 10 mmol/day. This avidity prevents potassium poor diets from resulting in hy-pokalemia unless they are maintained for a long time. On the other side of the potassium coin the kidney is able to ramp po-tassium excretion up to over 400 mmol/day. Because of this phenominal ability to excrete excess potassium, increased po-tassium intake is rarely the cause of persistant hyperkalemia. There are also clandestine sources of parenteral potassium:• Maintenance fluids• Penicillin G (1.7 mEq/1,000,000 units)• Hyperalimentation

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• Red cell transfusions• Dialysate

Cellular distributionSince 98.6% of total body potassium is found in the cells it should not be surprising that the forces that govern the distribu-tion of potassium into and out of the cells is a major factor gov-erning serum potassium. Movement of only 1% of the intracellu-lar potassium will double the serum potassium and likely kill the patient.Every cell membrane in the body is studded with Na-K-ATPase which serves to maintain the high intracellular potassium con-tent. These Na-K-ATPases are under physiologic control and factors which increase their ac-tivity lower the serum potassium and factors which decrease their activity increase potassium.Insulin stimulates Na-K-ATPase. This makes sense because in-sulin is released after eating which allows the body to use the newly arrived blood sugar but also it allows the body to safely store the newly arrived potas-sium.Activation of the ß-2 receptors stimulates the Na-K-ATPase and lowers the serum potassium. This is seen with endogenous epinephrine, norepinephrine, and acetylcholine. It has also been shown to occur with al-buterol and dobutamine. On the other hand, blocking the recep-tors with beta-blockers will in-crease the potassium.

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Acid-base status also influences the cellular distribution of po-tassium. During acidemia, there is an excess of hydrogen cati-ons in the blood. One of the buffers for this in the intracellular compartment. Hydrogen cations move into cells. All ion move-ment is ultimately electroneutral, so the movement of a cation into the cells must be balanced either by an anion moving in the same direction or a cation moving in the opposite direction.• If the acidosis is due to an inorganic acid (non-anion gap) then

hydrogen is exchanged for potassium. The opposite occurs with alkalemia.

• If the acidosis is due to an organic acid (think ketoacidosis, lactic acidosis) then the anion moves into the cell with the hy-drogen ion. In this situation no potassium moves out of the cell.

Renal potassium handlingThe kidney is responsible for excreting all of the potassium in-gested by the body. Potassium handling by the nephron is com-

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plex with potassium reabsorption early in the nephron and ex-cretion in the late nephron.

The critical concept that the students of renal physiology must take home is that renal excretion of potassium is entirely done by the cortical collecting tubule. The standard model for renal excretion is that plasma is filtered at the glomerulus and then the rest of the nephron reabsorbs any particle of value and ex-cretes additional waste products does not apply to potassium. The filtered potassium is not excreted. All of the filtered potas-sium is reabsorbed. Then in a second step excess potassium is secreted in the cortical collecting ducts.This complex mixture of reabsorption and secretion actually al-lows one to use a simplified model of renal potassium handling. One only has to worry about the CCD and can ignore the rest of the nephron.

Potassium handling at the CCDPotassium excretion is a multistep process:

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Proximal TubuleReabsorb two-thirds of filtered potassium Thick Ascending Limb

Loop of HenleReabsorb a quarter of filtered potassium

Distal convoluted tubuleReabsorb 5% of filtered po-tassium

Cortical collecting duct Only part of the nephron that secretes potassium

1. sodium is reabsorbed through the ENaC. Sodium moves down its concentration gradient.

2. The movement of sodium is electrogenic and results in a negative charge in the tubule.

3. Chloride in the tubule can be reabsorbed paracellularly. The more chloride that is reabsorbed the less potassium is se-creted.

4. Potassium flows down a electrical and chemical gradient into the tubule.

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ENaC1.

2.

3.

4.

Regulation of potassium excretionThe rate of potassium excretion is controlled by two factors:

1. Aldosterone2. Tubular flow (also called distal delivery of sodium)

Aldosterone is a steroid hormone secreted by the Zona Glomerulosa of the adrenal glands. Aldosterone secretion is stimulated by angio-tensin 2 and increased serum po-tassium. Aldosterone acts by in-creasing the number and activity of all the principle proteins involved in potassium secretion.Tubular flow is just a measure of how fast fluid is moving past the principle cells. If the fluid is sluggish due to decreased flow, secreted potassium accumu-lates in the tubule and disrupts the chemical gradient favoring potassium excretion. Addition-ally, high flow means enhanced sodium delivery. This sodium is critical for the initial step in po-tassium excretion: sodium re-absorption.The last important concept for renal potassium handling is understanding that aldosterone and tubular flow typically move in opposite direction. One of the chief determinants of aldosterone activity is volume status, when patients are hypovolemic aldosterone is increased, when patients are volume overloaded, aldosterone is suppressed. Tu-bular flow is also determined by volume status, when patients are hypovolemic, tubular flow slows. When they are hypervo-lemic flow increases.

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hypovolemic hypervolemic

Aldosterone

Tubular flow

increased decreased

decreased increased

This reciprocal relationship between aldosterone and tubular flow allows renal potassium handling to remain independent of volume status.

Tubular flow

Aldosterone

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HypokalemiaIf there isnʼt enough potassium...give some.

DefinitionPotassium less than 3.5 mmol/L is defined as hypokalemia. Low potassium can result in:• Hypertension• Increased stroke risk • Arrhythmias• Illeus• Rhabdomyolysis

EtiologiesThe causes of hypokalemia can best be categorized in the same way we broke down total body potassium handling: in-take, cellular distribution and renal secretion of potassium.

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decreased intake:• alcoholics• malnutrition• grey clay ingestion

Intracellular movement:• beta agonists• dobutamine• rapid cell growth

Renal losses• diuretics• hyperaldosteronism• decreased chloride delivery

-1.0

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Time (min)

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Saline 10 mg 20 mg

Allon Et al. Annals of Int Med; 1989: 110, 426-429.

Renal casuses of hypokalemia occur when the reciprocal rela-tionship of aldosterone and tubular flow breaks down and both of them are activated simultaneously:

Tubular flowAldosterone

The classic case of renal potassium loss is diuretic induced hy-

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Change in potassium after treatment with nebu-lized albuterol

pokalemia. In this situation, the diuretic directly increases distal delivery of sodium/tubular flow and by causing volume defi-ciency triggers an increase in aldosterone. So patients lose the reciprocal relationship of aldosterone and tubular flow and get both forces activated at the same time.In primary hyperaldosteronism, the increase in aldosterone is easy but the increase in tubular flow is less obvious. Increased aldosterone leads to hypertension which then induces a phe-nomena called pressure natriuresis which triggers an increase in tubular flow. Interestingly the pressure natriuresis is a late finding in primary hyperaldosteronism and the hypokalemia is delayed until that occurs.Vomiting is a special case of renal potassium loss leading to hy-pokalemia. First off vomiting does not cause hypokalemia be-cause of the potassium lost in the vomit. The potassium content of puke is pretty modest. Vomiting causes volume depletion which triggers the release of aldosterone. Vomiting also causes metabolic alkalosis. The increase in serum bicarbonate means that some of this bicarbonagte ends up being excreted in the urine. The bicarb in the urine nudges out chloride. Bicarbonate is not reabsorbed paracellularly, so there is no disruption of the electronegative tubule which enhances potassium excretion.

Consequences of low potassiumLow potassium increases fatal strokes in men

Low potassium predisposes to hypertension and correction of that potassium lowers the blood pressure.

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MAP Delta K

16 hypertensive patients with diureticinduced hypokalemia were started on 60mmol of KCl per day.Kaplan, N. M., Carnegie, A., Raskin, P., Heller, J. A. &Simmons, M. Potassium supplementation in hypertensivepatients with diuretic-induced hypokalemia. N. Engl. J.Med. 312, 746-749 (1985).

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SBP DBP AA SBP AA DBP

101 hypertensive patients RANDOMIZEDTO 120 mmol of KCl per day (blue)versus placebo (red).Svetkey, L. P., Yarger, W. E., Feussner, J. R., DeLong, E.& Klotman, P. E. Double-blind, placebo-controlled trial ofpotassium chloride in the treatment of mild hypertension.Hypertension 9, 444-450 (1987).

Hypokalemia produces EKG changes:• Flattening of T waves• Increased prominence of U waves (look at V4, 5, 6)• ST depression• Increased prominence of P waves• Inversion of T waves16

Low potassium predisposes to arrhythmia, especially in the peri-MI period.

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≤3.0 3.1-3.5 3.6-4.0 4.1-4.5 4.6-5.1 ≥5.2

VF, VFl, VT, AF VT, VF VF

TreatmentIf the potassium is low, give potassium. The potassium can be given IV or PO but oral is preferred. Use 20-40 mEq qd-q6h. KCl is superior to Kphos or K-acetate. Reserve IV potassium for patients who are NPO or have dangerously low potassium.Make sure you consider potassium sparing diuretics, especially for diuretic induced hypokalemia. Check and correct Mg defi-ciency.

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Complications of IV potassium replacement: hyperglycemia, volume overload, phlebitis and hyperkalemia (not pictured).

How much potassium to give? A standerd rule of thumb is to use the following formula: Four minus the current potassium times 100. This will correct roughly half the defecit and should mini-mize subsequent hyperkalemia.

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HyperkalemiaThe condition that will kill you in a hurry

Hyperkalemia is defined as a plasma potassium over 5.5 mEq/L. The primary clinical problems with high potassium is weak-ness and arrhythmias, specifically bradycardia and ventricular fibrillation.

Etiologies

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Extracellular movement:• Cell death• Tumor lysis syndrome• Rhabdomyolysis• Hemolysis• Hypothermia• Solute drag• Lack of insulin• Beta blockers• Digoxin• Metabolic

acidosis (inorganic)

Decreased renal K clearance• Renal failure• Heart failure• Potassium sparing diu-

retics• ACEi and ARB• RTA (type IV)• Hypoaldosteronism

Increased intake:oral• Salt substitutes

65 mmol/tsp• Shohlʼs solution

1 mmol/mL• Red clay• Kiwi 6.5 mmol• Banana 12 mmolparenteral• IVF• LR• TPN• Dialysate

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Control Mannitol270

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Potassium Osmolality

Kurtzman, N. A., Et. Al. Am. J. Kidney Dis. 15, 333-356 (1990).

5% rise in osmolality resultsin a 13% rise in K

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0

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contr

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Propan

olol

Phento

lamine

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Williams, M. E. et al. Catecholamine modulation of rapid potassium shifts during exercise. N. Engl. J. Med. 312, 823-827 (1985).

Hypothermia

Tumor lysis syndrome

Trauma

Pseudohyperkalemiasince there is a large amount of potassium in cells, a traumatic blood draw can cause hemolysis and artificially raise the potas-sium. Additionally blood samples with thrombocytosis and leu-kocytosis can cause falsely elevated potassium readings.

EKG Changes

Peaked Ts are the initial finding

Shortened QT interval

Widened QRS

Sinosoidal

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TreatmentThe treatment of hyperkalemia follows a multistep process. The first step is a specific therapy which acts as an antidote for the cardiac changes induced by hyperkalemia, calcium. After that all of the therapies aim at reducing the potassium.

CalciumIf EKG signs are present give calcium. Calcium chloride is more effective than calcium gluconate because a gram of CaCl con-tains three times as much calcium (0.68 mmol) as a gram of calcium gluconate (0.23 mmol). The onset of action is essen-tially instant and lats about 1 hour. The calcium can be repeated and should be repeated until the EKG normalizes.Most text books say that calcium should be avoided if the pa-tient has digoxin toxicity. In that case use of digoxin FAB will rapidly and reliably lower the serum potassium.

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Remove potassium from the body

Stop oral intakeLook for and eliminate stealth potassium: maintenance IVs, CVVH fluid, Penicillin G, CHA, dietary sources (salt substitutes).

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Induce intracellular shift:• insulin• albuterol• correct hyperglycemia• correct digoxin toxicity

Stop all K intake Oral• Salt substitutes• Shohlʼs solution• Red clay• protein supplements Parenteral• IVF• LR• TPN• Dialysate

Remove K from the body:• diuretics• increase Na intake• kayexylate• dialysis

Move extracellular potassium into the cellsThe traditional therapy for this is sodium bicarbonate and insulin with glucose. Blumberg Et al. Amer J Med; 1988: 85, 507-512. After Blumberg showed no hypokalemic effect after 60 minutes he followed it up with an extended protocol for 6 hours and found a minimal reduction of potassium after 4.

The use of albuterol is a newer therapy for hyperkalemia but is quite effective and is synergistic with insulin and glucose:

The orders to get optimal hypokalemic effect are:

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Time (min)

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ge in

K

NaHCO3 8.4% NaHCO3 1.4%Epinephrine Insulin GlucoseDialysis

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Time (min)

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ge in

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p>0.05 P<0.05

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Time (min)

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ge in

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Saline 10 mg 20 mg

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Time (min)

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Insulin Albuterol Combination

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1. 10 units IV insulin2. 50 g of D503. repeat blood sugar q 1 hour for 6 hours4. Albuterol 20 mg per nebulizer

Remove the potassium from the body:Increase the excretion of potassium via the kidneys by rehydrat-ing patients with normal saline and giving a trial of furosemide (Lasix). If the patient has kidney disease use 20 x sCr IV push.Sodium polystyrene resins (Kayexalate) in patients whose kid-neys donʼt work, use 30 grams in adults.Call nephrology early for dialysis.

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Joel M. Topf, MDNephrology

248.470.8163