Potassium For Med Students

Potassium

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Joel M. Topf, M.D. Attending Nephrologist PBFluids.blogspot.com 248.470.8163

Introduction Potassium: Cool electrolyte Potassium is a favorite electrolyte of both medical students and renal physiologists. It is illustrative, important and relevant in ways that most other electrolytes are not. Potassium physiology is straight forward and logical. It is the electrolyte that demonstrates much of the elegance of renal physiology. Potassium follows logical and easily visualized rules. In addition to being a great exercise in renal physiology it is an important ion with severe implications from disregulation: How do cardiac surgeons stop the heart after 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 potassium. Lastly, potassium disregulation is common, so lessons learned can be used on a daily basis.

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Table of Contents Potassium Total body potassium Potassium handling in three steps

4 4 5

Potassium intake

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Cellular distribution

6

Renal potassium handling

7

Potassium handling at the CCD

8

Regulation of potassium excretion

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Hypokalemia Definition Etiologies Consequences of low potassium Treatment

Hyperkalemia Etiologies Pseudohyperkalemia

EKG Changes Treatment

12 12 12 14 17

19 19 22

22 24

Calcium

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Remove potassium from the body

25

Stop oral intake

25

Move extracellular potassium into the cells

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Remove the potassium from the body:

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Potassium Potassium is the primary intracellular cation

Total body potassium Potassium is the dominant intracellular cation and because the intracellular compartment is twice the size of the extracellular compartment it is the most common electrolyte in the body. The intracellular K concentration runs from 120-153 mmol/ L The extracellular concentration 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 potassium pills come in? what is the typical dose of IV potassium? How does that compare to the extracellular potassium content?

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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 intake Diets 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 potassium avid and can reduce potassium losses to 10 mmol/day. This avidity prevents potassium poor diets from resulting in hypokalemia unless they are maintained for a long time. On the other side of the potassium coin the kidney is able to ramp potassium excretion up to over 400 mmol/day. Because of this phenominal ability to excrete excess potassium, increased potassium 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 5

• Red cell transfusions • Dialysate Cellular distribution Since 98.6% of total body potassium is found in the cells it should not be surprising that the forces that govern the distribution of potassium into and out of the cells is a major factor governing serum potassium. Movement of only 1% of the intracellular 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 content. These Na-K-ATPases are under physiologic control and factors which increase their activity lower the serum potassium and factors which decrease their activity increase potassium. Insulin stimulates Na-K-ATPase. This makes sense because insulin 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 potassium. 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 albuterol and dobutamine. On the other hand, blocking the receptors with beta-blockers will increase the potassium. 6

Acid-base status also influences the cellular distribution of potassium. During acidemia, there is an excess of hydrogen cations in the blood. One of the buffers for this in the intracellular compartment. Hydrogen cations move into cells. All ion movement 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 hydrogen ion. In this situation no potassium moves out of the cell.

Renal potassium handling The kidney is responsible for excreting all of the potassium ingested by the body. Potassium handling by the nephron is com7

plex with potassium reabsorption early in the nephron and excretion in the late nephron. Distal convoluted tubule Reabsorb 5% of filtered potassium

Cortical collecting duct Only part of the nephron that secretes potassium

Proximal Tubule Reabsorb two-thirds of filtered potassium

Thick Ascending Limb Loop of Henle Reabsorb a quarter of filtered potassium

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 excretes additional waste products does not apply to potassium. The filtered potassium is not excreted. All of the filtered potassium is reabsorbed. Then in a second step excess potassium is secreted in the cortical collecting ducts. This complex mixture of reabsorption and secretion actually allows 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 CCD Potassium excretion is a multistep process: 8

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

1.

ENaC 2.

4.

3.

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Regulation of potassium excretion The rate of potassium excretion is controlled by two factors: 1. Aldosterone 2. 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 angiotensin 2 and increased serum potassium. Aldosterone acts by increasing 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 accumulates in the tubule and disrupts the chemical gradient favoring potassium excretion. Additionally, high flow means enhanced sodium delivery. This sodium is critical for the initial step in potassium excretion: sodium reabsorption. 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. Tubular flow is also determined by volume status, when patients are hypovolemic, tubular flow slows. When they are hypervolemic flow increases. 10

hypovolemic

hypervolemic

Aldosterone

increased

decreased

Tubular flow

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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Hypokalemia If there isnʼt enough potassium...give some.

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

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

decreased intake: • alcoholics • malnutrition • grey clay ingestion

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

Renal losses • diuretics • hyperaldosteronism • decreased chloride delivery

0.4 0.2

Change in K

0.0 -0.2

0

30

60

90

120

-0.4 -0.6 -0.8 -1.0 Time (min) Saline

10 mg

20 mg

Change in potassium after treatment with nebulized albuterol Allon Et al. Annals of Int Med; 1989: 110, 426-429.

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

Tubular flow

Aldosterone

The classic case of renal potassium loss is diuretic induced hy13

pokalemia. In this situation, the diuretic directly increases distal delivery of sodium/tubular flow and by causing volume deficiency 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 phenomena 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 hypokalemia. First off vomiting does not cause hypokalemia because 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 potassium Low potassium increases fatal strokes in men

Low potassium predisposes to hypertension and correction of that potassium lowers the blood pressure. 14

1 0 MAP

Delta K

-1 -2 -3 -4 -5 -6

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

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0 -2 -4

SBP

DBP

AA SBP

AA DBP

-6 -8 -10 -12 -14 -16 -18 -20

101 hypertensive patients RANDOMIZED TO 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 of potassium 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 waves 16

Low potassium predisposes to arrhythmia, especially in the periMI period.

50 40 30 20 10 0 ≤3.0

3.1-3.5 3.6-4.0 4.1-4.5 4.6-5.1

VF, VFl, VT, AF

VT, VF

≥5.2

VF

Treatment If 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 deficiency.

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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 minimize subsequent hyperkalemia.

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Hyperkalemia The 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 weakness and arrhythmias, specifically bradycardia and ventricular fibrillation.

Etiologies

Increased intake: oral • Salt substitutes 65 mmol/tsp • Shohlʼs solution 1 mmol/mL • Red clay • Kiwi 6.5 mmol • Banana 12 mmol parenteral • IVF • LR • TPN • Dialysate

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

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6.0

310

5.5 300 5.0 4.5

290

4.0 280 3.5 3.0

270 Control Potassium

Mannitol Osmolality

5% rise in osmolality results in a 13% rise in K Kurtzman, N. A., Et. Al. Am. J. Kidney Dis. 15, 333-356 (1990).

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2.0

1.5

1.0

0.5

in e Ph

en t

ol a

m

ol op an ol Pr

co

nt ro l

0

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

Trauma

Tumor lysis syndrome

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Pseudohyperkalemia since there is a large amount of potassium in cells, a traumatic blood draw can cause hemolysis and artificially raise the potassium. Additionally blood samples with thrombocytosis and leukocytosis can cause falsely elevated potassium readings.

EKG Changes Peaked Ts are the initial finding

Shortened QT interval

Widened QRS

Sinosoidal

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Treatment The 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. Calcium If EKG signs are present give calcium. Calcium chloride is more effective than calcium gluconate because a gram of CaCl contains three times as much calcium (0.68 mmol) as a gram of calcium gluconate (0.23 mmol). The onset of action is essentially 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 patient 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 all K intake Oral • Salt substitutes • Shohlʼs solution • Red clay • protein supplements Parenteral • IVF • LR • TPN • Dialysate

Induce intracellular shift: • insulin • albuterol Remove K from the body: • correct hyperglycemia • diuretics • correct digoxin toxicity • increase Na intake • kayexylate • dialysis

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

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Move extracellular potassium into the cells The 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. 0.3

-0.1 0 -0.3 -0.5

0.1

10

20

30

40

50

-0.1

60 Change in K

Change in K

0.3 0.1

-0.7 -0.9 -1.1

0

60 120 180 240 300 360

-0.3 -0.5 -0.7 -0.9 -1.1

-1.3 -1.5

-1.3 -1.5

Time (min) NaHCO3 8.4% Epinephrine Dialysis

Time (min) p>0.05

NaHCO3 1.4% Insulin Glucose

P<0.05

The use of albuterol is a newer therapy for hyperkalemia but is quite effective and is synergistic with insulin and glucose: 0.0

0.4

0

0.2

0

30

60

90

120

-0.4 -0.6

Change in K

Change in K

30

45

60

-0.3

0.0 -0.2

15

-0.6 -0.9 -1.2

-0.8 -1.5

-1.0

Time (min)

Time (min) Saline

10 mg

20 mg

Insulin

Albuterol

The orders to get optimal hypokalemic effect are: 26

Combination

1. 10 units IV insulin 2. 50 g of D50 3. repeat blood sugar q 1 hour for 6 hours 4. Albuterol 20 mg per nebulizer Remove the potassium from the body: Increase the excretion of potassium via the kidneys by rehydrating 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 kidneys donʼt work, use 30 grams in adults. Call nephrology early for dialysis.

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Joel M. Topf, MD Nephrology 248.470.8163

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