potassium disorders

Potassium Disorders

Jerry Hladik, MD

UNC-Chapel Hill

Case 1

A 62 year old male presents to the emergency room with a 2 day history of weakness. His recent history is significant for gouty arthritis for which he was taking over the counter ibuprofen.

140 106 76 7.8 15 10

100

140 104 10 4 24 1

100

Normal Values

Case 2

A 56 year old female presents with a 2 day history of weakness. On physical exam she is diffusely weak and is unable to sit up. The blood pressure is 210/105 mmHg. There is no edema.

140 96 20 1.9 32 1.4

100

140 104 10 4 24 1

100

Normal values

Outline

• Potassium distribution in the ECF and ICF and factors that alter K distribution.

• Renal tubular potassium regulation and excretion

• Differential diagnosis of hyperkalemia and hypokalemia

Physiologic Effects of Potassium

• Major determinant of the resting membrane potential

• Hypokalemia– may precipitate cardiac arrhythmias

• Hyperkalemia – life threatening cardiac conduction disturbances

and arrhythmias

3Na+

2K+ATPase

Transcellular K+ Distribution

K+cell = 140-160 mEq/L

K+e = 4-5 mEq/L

Relationship Between [K+]serum and Total Body Potassium in 70 kg Adult

Serum[K+]mEq/L

Total Body Potassium

Normal-150 mEq +150 mEq

2

3

4

5

6

Potassium Distribution

ECF

ICF3920 mEq

80 mEq

98%

2%

Potassium Content in Fruits and Vegetables

Amount of PotassiumMilligrams mEq

Potato with skin 844 mg 20

3 Oz. Dried Fruit 796 mg 20

10 Dried Prunes 626 mg 16

1 Banana 451 mg 11

Tomato 254 mg 6.5

1 Kiwi 252 mg 6.5

8 Oz. Glass of 250 mg 6.5

Orange Juice

1Grapefruit 158 mg 4

A 24 y.o male returns home to visit his mother. For breakfast she serves orange juice (of which he drinks 3 large glasses), and a bowel of fruit comprised of 2 bananas, 1 grapefruit, and 1 kiwi.

What would happen to the serum potassium concentration if all of the ingested potassium remained in the extracellular space?

Ingested Potassium = 52 mEqExtracellular Potassium = 80 + 52 = 132 mEqSerum K Concentration = 132 mEq/15 L = 8.8 mEq/L !

Components of Potassium Homeostasis

Intake ECF

ICF

Distribution

Excretion

90% Kidney

10% Colon

Insulin

Aldosterone

Renal Tubular Potassium Handling

Filtered load600-700 mEq

per day

K+ Reabsorption60-70%

K+ Reabsorption20-30% K+ Secretion

Urinary Excretion90mEq/day

Urinary Potassium Excretion

• Normal kidneys have the capacity to excrete 500-600 mEq per day (average K+ excretion 40-100 mEq/day).

• The key site of renal potassium excretion regulation occurs at the cortical collecting duct.

Cortical Collecting Duct - Principle Cells

Na+

K+

3Na+

2K+

AldosteroneR-Aldo

Cl-

Peritubularcapillary

Tubular lumen

ATPase

Na+

Cortical Collecting Duct

ATPase

ATPase

ATPase

Tubular lumen PeritubularCapillary

Principle Cell

Intercalated Cell

K+

H+

OH- + CO2 HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

Cl-

K+

Na+

ATPase

3Na+

2K+

R-Aldo

NH3NH3H+ +

NH4+

Na+

Aldosterone

Mechanisms Leading to Hyperkalemia

• Impaired entry into cells

• Increased release from cells

• Decreased urinary excretion

3Na+

2K+ATPase

K+

H+

GlucoseInsulinDigoxinβ-blockersCell injury

Hyperkalemia – Redistribution: ICFECF

Factors that Impair Urinary K+ Excretion

• Collecting duct lumen relatively more electropositive

• Decreased flow and sodium delivery to the CCD

• Decreased aldosterone production or activity

Effect of Amiloride

Predict changes in the following:

• Relative lumen charge• Renal K+ excretion• Serum potassium• Renal H+ excretion• Arterial pH ATPase

ATPase

PeritubularCapillary

OH- + CO2 HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

K+

ATPase

3Na+

2K+

R-Aldo

AmilorideNa+ Channel

Amiloride

Aldosterone

Tubular lumen

Hyperkalemia: Decreased Renal Excretion

• Volume depletion decreased flow in CCD• Decreased renin-AII-aldo production

– NSAIDS renin

– ACEI AII

– Heparin aldosterone production

– Spironolactone aldosterone activity

• Inhibition of CCD Na+ channel– Amiloride, triamterene, trimethoprim, pentamidine

ECG Changes due to Hyperkalemia

ECG Changes of Hyperkalemia

Serum K+ (mEq/L) ECG

9 Sinoventricular V-fib

8 Atrial standstill Intraventricular block

7 Tall T wave. Depressed ST segment

6 Tall T wave. Shortened QT interval

Effect of i.v. Ca2+ on Membrane Potentials in Hyperkalemia

-90

-60

- 30

0

+30

Em

Et

Normal K+e

Et

Em

i.v. Calcium

Em

Et

K+e

Treatment of Hyperkalemia

Therapy Mechanism of Action

Calcium Stabilization of Membrane Potential

Insulin Increased K+ entry into CellsBeta-2 AgonistsBicarbonate (if pHa<7.2 in setting of

acidosis)

Dialysis Potassium removalCation Exchange Resin (sodium polystyrene = Kayexalate)

Differential Diagnosis of Hypokalemia

• Increased entry into cells

• Inadequate intake or GI losses

• Urinary losses

3Na+

2K+ATPase

K+

Hypokalemia: Redistribution: ECFICF

Insulinβ-2 agonistsAlkalosis

Barium poisoningHypokalemic periodic paralysis

Factors that Enhance Urinary K+ Excretion

• Lumen of CCD more electronegative

• Enhanced flow and sodium delivery to the CCD

• Increased aldosterone

Thiazide Diuretics

Loop diuretics

Na+K+2Cl--

BloodLumen

Loop diuretics

Na+Cl-

Thiazide diuretics

Sites of Action of Diuretics

Lumen Blood(Defect = Bartter’s)

(Defect = Gitelman’s)

Interpretation of Urinary K+ in the Setting of Hypokalemia

GI Losses or prior Renal K Loss or

Diuretic Therapy Current Diuretic

Use

24o Urine K < 20 mEq > 30 mEq

FeK < 6 % > 10 %

Ser

um [

HC

O3-

]U

pHU

[Cl- ]35

30

25

20

7.0

5.5

4.0503010

Generation Phase Late Maintenance Phase

Volume Depletion

Metabolic Alkalosis in Vomiting

Early Maintenance Phase

Effect of Gastric Loss of HCl, Na+/H2O (Volume)

Predict changes in the following:

1. Relative lumen charge2. Renal K+ excretion3. Serum potassium4. Renal H+ excretion5. Arterial pH

ATPaseATPase

Tubular lumenPeritubularCapillary

OH- + CO2 HCO3-

T

Cl-

H2O

H+ 3Na+

2K+

K+

Na+

ATPase

3Na+

2K+

R-Aldo Aldosterone

Na+

HCO3-

Na+

ba

lanc

e

-200

200

Days 2 4 6 8 10 12 14 16 18

Uri

ne [

Na+ ]

mE

q/L

10

15

20

EC

F V

ol(L

)

18

21

Mea

n ar

teri

alP

ress

ure

100

110

90

15

0

Aldosterone

Aldosterone Escape

Urine Na+ and Cl- in the Differential Diagnosis of Metabolic

Alkalosis and Hypokalemia

Urine ElectrolytesNa+ Cl-

Condition (meq/L)

VomitingAlkaline urine >15 <15Acidic urine <15 <15

DiureticDrug active >15 >15Remote use <15 <15

Hyperaldosteronism >15 >15

Case 2

A 56 year old female presents with a 2 day history of weakness. On physical exam she is diffusely weak and is unable to sit up. The blood pressure is 210/105 mmHg. There is no edema.

140 96 20 1.9 32 1.4

100

140 104 10 4 24 1

100

Normal values

Case 2 Continued

Urine [Na+] = 75 mEq/L

Urine [Cl-] = 100 mEq/L

FeK = 20%

What is the most likely diagnosis?