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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. 106 76 7.8 15 10. 100.

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Potassium disorders

Potassium Disorders

Jerry Hladik, MD

UNC-Chapel Hill


Case 1
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.

  • 106 76

  • 7.8 15 10

100

Normal Values

140 104 10

4 24 1

100


Case 2
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.

  • 96 20

  • 1.9 32 1.4

100

140 104 10

4 24 1

100

Normal values


Outline
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
Physiologic Effects of Potassium

  • Major determinant of the resting membrane potential

  • Hypokalemia

    • may precipitate cardiac arrhythmias

  • Hyperkalemia

    • life threatening cardiac conduction disturbances and arrhythmias


Transcellular K+ Distribution

3Na+

ATPase

2K+

K+cell = 140-160 mEq/L

K+e = 4-5 mEq/L


Relationship between k serum and total body potassium in 70 kg adult
Relationship Between [K+]serum and Total Body Potassium in 70 kg Adult

6

5

Serum

[K+]

mEq/L

4

3

2

-150 mEq

Normal

+150 mEq

Total Body Potassium


Potassium distribution
Potassium Distribution

ECF

80 mEq

2%

ICF

3920 mEq

98%


Potassium content in fruits and vegetables
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 mEq

Extracellular Potassium = 80 + 52 = 132 mEq

Serum K Concentration = 132 mEq/15 L = 8.8 mEq/L !


Components of potassium homeostasis
Components of Potassium Homeostasis 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.

ICF

Distribution

90% Kidney

Insulin

Excretion

Aldosterone

ECF

Intake

10% Colon


Renal Tubular Potassium Handling 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.

Filtered load

600-700 mEq

per day

K+ Reabsorption

20-30%

K+ Secretion

K+ Reabsorption

60-70%

Urinary Excretion

90mEq/day


Urinary potassium excretion
Urinary Potassium Excretion 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.

  • 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 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.

Na+

Peritubular

capillary

Na+

3Na+

ATPase

2K+

Tubular lumen

K+

R-Aldo

Aldosterone

Cl-


Cortical Collecting Duct 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.

Na+

Tubular lumen

Peritubular

Capillary

Na+

3Na+

Principle Cell

ATPase

2K+

K+

Aldosterone

R-Aldo

Cl-

ATPase

3Na+

H+

ATPase

Intercalated Cell

H2O

2K+

T

HCO3-

OH- + CO2

K+

NH4+

ATPase

Cl-

H+

H+ +

NH3

NH3


Mechanisms leading to hyperkalemia
Mechanisms Leading to Hyperkalemia 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.

  • Impaired entry into cells

  • Increased release from cells

  • Decreased urinary excretion


Hyperkalemia redistribution icf ecf
Hyperkalemia – Redistribution: ICF 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.ECF

  • H+

  • Glucose

  • Insulin

  • Digoxin

  • β-blockers

  • Cell injury

3Na+

ATPase

2K+

K+


Factors that impair urinary k excretion
Factors that Impair Urinary K+ Excretion 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.

  • Collecting duct lumen relatively more electropositive

  • Decreased flow and sodium delivery to the CCD

  • Decreased aldosterone production or activity


Effect of amiloride
Effect of Amiloride 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.

Tubular lumen

  • Predict changes in the following:

  • Relative lumen charge

  • Renal K+ excretion

  • Serum potassium

  • Renal H+ excretion

  • Arterial pH

Aldosterone


Hyperkalemia decreased renal excretion
Hyperkalemia: Decreased Renal Excretion 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.

  • 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 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.


ECG Changes of Hyperkalemia 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.

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. Ca 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.2+ on Membrane Potentials in Hyperkalemia

+30

0

i.v. Calcium

-

30

Et

Em

Em

-60

Et

Et

-90

Em

Normal

K+e

K+e


Treatment of hyperkalemia
Treatment of Hyperkalemia 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.

Therapy Mechanism of Action

Calcium Stabilization of Membrane

Potential

Insulin Increased K+ entry into Cells

Beta-2 Agonists

Bicarbonate (if pHa<7.2 in setting of

acidosis)

Dialysis Potassium removal

Cation Exchange Resin

(sodium polystyrene

= Kayexalate)


Differential diagnosis of hypokalemia
Differential Diagnosis of Hypokalemia 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.

  • Increased entry into cells

  • Inadequate intake or GI losses

  • Urinary losses


Hypokalemia: Redistribution: ECF 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.ICF

  • Insulin

  • β-2 agonists

  • Alkalosis

  • Barium

  • poisoning

  • Hypokalemic

  • periodic

  • paralysis

3Na+

ATPase

2K+

K+


Factors that enhance urinary k excretion
Factors that Enhance Urinary K+ Excretion 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.

  • Lumen of CCD more electronegative

  • Enhanced flow and sodium delivery to the CCD

  • Increased aldosterone


Sites of Action of Diuretics 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.

Thiazide Diuretics

Loop diuretics

Blood

Lumen

(Defect = Bartter’s)

Na+

Cl-

Lumen

Blood

Na+

K+

2Cl--

Thiazide diuretics

Loop diuretics

(Defect = Gitelman’s)


Interpretation of Urinary K 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.+ 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 %


Metabolic Alkalosis in Vomiting 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.

35

Volume Depletion

30

Serum [HCO3-]

25

20

7.0

UpH

5.5

4.0

50

U[Cl-]

30

10

Early Maintenance Phase

Generation Phase

Late Maintenance Phase


Effect of gastric loss of hcl na h 2 o volume

Tubular lumen 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.

Peritubular

Na+

Capillary

Na+

3Na

+

ATPase

2K

+

K+

R

-

Aldo

Aldosterone

3Na

+

H+

ATPase

ATPase

H

O

2K

+

2

T

HCO

-

OH

-

+ CO

3

2

Cl

-

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

Predict changes in the following:

1. Relative lumen charge

2. Renal K+ excretion

3. Serum potassium

4. Renal H+ excretion

5. Arterial pH

HCO3-


Aldosterone Escape 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.

Aldosterone

110

Mean arterial

Pressure

100

90

21

ECF Vol

(L)

18

15

20

15

Urine [Na+]

mEq/L

10

200

Na+ balance

0

-200

Days

8

10

12

14

16

18

2

4

6


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

Urine Electrolytes

Na+ Cl-

Condition (meq/L)

Vomiting

Alkaline urine >15 <15

Acidic urine <15 <15

Diuretic

Drug active >15 >15

Remote use <15 <15

Hyperaldosteronism >15 >15


Case 2 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.

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.

  • 96 20

  • 1.9 32 1.4

100

140 104 10

4 24 1

100

Normal values


Case 2 continued
Case 2 Continued 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.

Urine [Na+] = 75 mEq/L

Urine [Cl-] = 100 mEq/L

FeK = 20%

What is the most likely diagnosis?


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