Potassium Disorders
K Homeostasis
98% of K is Intracellular (IC) / 2 % is extracellular (EC).
Resting cell membrane potential (RMP) is determined by Nernst equation: RMP = 61.5 log (IC-K+/EC- K+) so RMP is determined by ratio of IC-K+ to EC- K+.
This ratio (NOT ABSOLUTE CONCENTRATION) has cardiac implications on: conduction, contraction and rhythm.
Distribution of K+ (in mEq)
- Muscle(3000)
; RBC(235); Liver(200);Urine (92); ECF(65)
- Kidney primarily regulates steady state: intake 100mEq; excrete 8mEq in sweat and 92 in urine.
- Total Body K+= 50 mEq/Kg body mass = 3500 mEq
Factors that influence transcellular distribution of K+: Acid/ base status (see below)
Hormonal Control of K:
- (1) Insulin: Drives K into cells, and is increased by hyperkalemia.
- (2) Catecholamines: Drive K into cells by acting on
b adrenergic receptors. b -agonistÞ ß K, b -blockersÞ Ý K.
(3) Aldosterone: Ý K excretion.
(4) Thyroid hormone: Not clinically significant, possibly Ý Na/K ATPase synthesis.
Acid/Base effects:
Þ H enters cells, K leaves cells (buffering mechanism) to maintain neutrality. Alkalosis usually results.
Alkalosis Þ H exits cells, K enters cells. Acidosis usually results.
Sites of tubular K+ transport: Fine-tuning happens in the distal tubules (DT) and collecting ducts (CD)
- Proximal Tubule
– Normally all of the K+ is passively reabsorbed here.
- Distal Tubule
and Collecting Duct – Aldosterone regulates K excretion in 2 ways:
Ý Na/K ATPase, and Ý apical Na and K channels. Na is critical in this exchange. In volume depleted states (CHF, cirrhosis, Nephrotic syndrome) where there is no Na delivery to the DT there is no K loss Þ hyperkalemia.
Hypokalemia
Estimating K deficit
[K+]plasma reflects total body K+ – note: must rule out transcellular shift which could result from Alkalosis or (less likely) Hypokalemic Periodic Paralysis.
Normal [K+]plasma=3.6-5.2 mEq - [K+]plasma=3.0 indicates a mild depletion of 200-400 mEq/L (symptoms range from: asymptomatic, to weakness and constipation)
Severe depletion to [K+]plasma=2.5 mEq - can lead to muscle necrosis, paralysis, impaired respiratory function.
[K+]plasma < 2 - can lead to Renal problems: ß concentrating ability, slight ß GFR, and renal acid secretion.
EKG manifestations of Hypokalemia:
- delayed phase 2 and 3 reporlarization
Þ cell can be activated earlier Þ Arrhythmias
delayed phase 0 up stroke Þ depressed ST segment, Flat T wave and Ý u wave voltage
Four Major causes of hypokalemia
(1) ß dietary intake
(2) Ý entry into cells: Metabolic alkalosis, Ý ß-adrenergic activity (endogenous catecholamines or ß-agonists), Insulin
(3) GI losses: Diarrhea, Enteric fistula, Vomiting or nasogastric suction, Drugs: Laxatives, Cation exchange resins
(4) Renal losses: Mineralocorticoid excess (primary hyperaldosteronism, secondary to RAA, Congenital adrenal hyperplasia, Cushing’s syndrome ), vomiting, Renal tubular acidosis (types I and II), Drugs: Thiazide-like diuretics, Loop diuretics, Mineralocorticoids
Urinary K helps differentiate which causes are involved:
- urinary K < 10-15 mEq = Extra renal losses
- urinary K > 10-15 mEq = Renal losses
Three Renal Ion Transport Defects causing Hypokalemia
(1) Bartters Syndrome: (Mimics furosimide) = defect in Cl- reabsorption in the thick ascending limb of LoH. Patients present with Hypokalemic alkalosis, Ý renin and aldo, normal BP, varying degrees of ß Mg.
(2) Gitelmans Syndrome: (Mimics thiazides) defect in Cl- reabsorption in the early distal tubule Þ ß K, Ca (urine), Mg
(3) Liddles’s Syndrome: (pseudohyperaldosteronism) genetic mutation Þ Ý Na resorption through apical DT channels. Patients present with volume HTN, ß K renin and aldo, metabolic alkalosis.
Five Treatment Principles: Cautious replacement of K
- (1) Correct associated fluid and electrolyte disorders
- (2) Select correct salt (type of K used) - Oral K is preferred, but IV K is indicated if NPO or in ongoing loss: 10 mEq/hr is safe – never over 20 mEq/hr
- (3) Discover underlying cause
- (4) Go slow!
- (5) Monitor
Hyperkalemia
Symptoms:
- NM
– Paresthiesia, Paralysis
- Cardiac
– Contractility,ß Conduction (ß RMP Þ ß de and Ý re-polarization)
EKG manifestations of Hyperkalemia
Peaked T wave, widened QRS, Ý PR interval; ß P wave merges with QRS Þ sine wave Þ Vfib/Asystole
Causes of Hyperkalemia
Ý excretory burden - (Exogenous or Endogenous –i.e. muscle breakdown)
Transcellular redistribution – due to b blockers and acidosis (butß shift in lactic acidosis – reason unknown).
Ý blood osmolarity (glucose) in the face of ß insulin Þ Hyperkalemia
Artifactual – ex: Hemolysis of RBCs when drawn through too small a caliber needle, myloproliferative state (Multiple Myeloma)
ß excretion:
(1) Acute Renal Failure – ß in GFR to <15mL/min (In chronic or less severe renal failure K is normal)
(2) ß effect of Aldosterone – impaired renin or aldo production or tubular resistance to aldosterone
(3) Other drugs – ACEI, heparin, cyclosporin
(4) Hypoaldosteronism - Adrenal insufficiency (AD), K sparing diuretics (triamteren, amiloride, trimethoprin), Idiopathic Hyporeninemic hypoaldosteronism (patients are usually old, have DM, and mild renal insufficiency.
- 50% of hyperkalemia
, 50% have acidosis (Type IV RTA), pathogenesis is unknown, Diagnosis: ß renin and aldo after appropriate stimulation)
Treatment of Hyperkalemia - get rid of the K
- if No ECG changes
(K 5-7 mEq/L):
- Exchange resins
bind K in GI tract (act slowly)
- Treat underlying disorder
- if QRS widening
(K > 7-8 mEq):
- Immediate
: Start with IV Ca++ (5-10 mEq) this antagonizes the membrane action
- 30-60 min
: start Insulin and glucose (HCO3- may be of benefit); promotes K entry into cells
- 2-3 h
: attempt K removal with exchange resins, Mineralocorticoids if no renal failure, Dialysis if renal failure.
Note: In DKA plasma concentration of K is increased because of acidosis but Total Body K is decreased. Therefore treat hyperglycemia, not hyperkalemia