potassium disorders jerry hladik, md unc-chapel hill
TRANSCRIPT
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?