Potassium Homeostasis & Its disorders By Dr. Mohammad El-Tahlawi

Objectives Potassium homeostasis Hypokalamia Definition Causes Effects Diagnosis Treatment

Potassium play an important role in: 1-Electerophysiology of cell membrane for all cells in which polarization- depolaization cycles are functionally relevant(cardiac and neuromuscular cells). 2-Carbohydrates and protien synthesis

POTASIUM DISTRIBUTION Extracellular 2% 70 meq Intracellular 98% 3430 meq Plasma 20% 15 meq Na-K ATPase K content = 50 meq/kg In 70 kg Total body K = 3500 meq

K level in meq / L K=140 meq/L Extra cellular K=4 meq/L (3.5-4.5meq) Intracellular K=140 meq/L Extra cellular K=4 meq/L (3.5-4.5meq)

intracellular K deficit Decrease in plasma K from 4 - 3 meq/L intracellular K deficit BY 100 - 200 meq

intracellular K deficit Decrease in plasma K from 3 - 2 meq/L intracellular K deficit BY 200 - 400 meq

Plasma K concentration Correlates poorly with the total body k deficit

Plasma potassium concentration Intake Intercompartmental distribution Potassium Excretion

Dietary K intake = 80 meq/day Excretion = 70 meq/day (urine). = 10 meq/day (GIT).

Regulation of K excretion The major determinant of urinary K excretion Extra cellular K Aldesterone level Tubular flow rate

Intercompartmental shift of Potassium 1- Extracellular pH. 2- Circulating insulin level. 3- Circulating catecholamine activity. 4- Plasma osmolality. 5- Hypothermia. 6- Exercise.

pH Insulin Hypothermia Rewarming Sympathetic activity K 0.6 meq/L every.01 Change in pH Insulin Na-K ATPase Acidosis Alkalosis Hypothermia Rewarming CELL B2-agonist B2-blokade Sympathetic activity (Na-K ATPase) Plasma osmolality increase K 0.6meq/L per increase10mosm/L

HYPOKALEMIA

HYPOKALAEMIA Causes: (K ion less than 3.5 meq/L) 1-Intercompartmental shift of K. 2-Increase k loss. 3-Inadequate k intake.

Intercompartmental shift of K: Causes of hypokalamia Intercompartmental shift of K: Alkalosis Insulin administration B2 adrenergic agonist Hypothermia Treatment of megaloplastic anaemia Periodic paralasis Transfusion of frozen blood

Increase K losses (Renal or extrarenal) Renal: Causes of hypokalamia Increase K losses (Renal or extrarenal) Renal: Diuretics Increase mineralocorticiod activity Renal tubular acidosis Ketoacidosis Hypomagesaemia Urinary diversion with long ileal loop Carbinecillin and Amphotericin B Prim and Sec hyper alderostenism

Extrarenal: Decrease K intake GIT : Diarrhea,Vomiting,Fistula, Causes of hypokalamia Extrarenal: GIT : Diarrhea,Vomiting,Fistula, Laxative abuse,Urinary diversion. Sweet Dialysis Decrease K intake

Effects of hypokalemia Most of the patients are asymptomatic until K level below 3 meq/L. Cariovascular effects are most prominent

Effects of hypokalamia Cardiovascular ECG changes Dysrhythmia Myocardial dysfunction Myocardial fibrosis Orthostatic hypotension Increase digitalis toxicity

Effects of hypokalamia Prominent U - wave Flat T Depressed ST segment Normal Decreasing Serum K + Cardiovascular ECG changes T wave flattening Prominent U wave ST segment depresion Increase P wave amplitude Prolongation of PR interval

Effects of hypokalamia Neuromuscular Skletal ms. Weakness up to respiratory failure. Tetany Rhabdomyolysis Ileus , Urine retention Renal Polyuria Increase amonium production Increase HCO3 reabsorption Increase Na retension Increased renin secretion→ increase AngII→ thirst

Effects of hypokalamia Metabolic Decrease insulin secretion Decrease growth hormone secretion Decrease aldesterone secretion Hormonal Negative nitrogen balance Encephalopathy in liver disease

Approach to diagnosis

Hypokalemia Urine K Urine Chloride Less than 30 meq/L More than 30meq/L Urine Chloride Diarrhea Less than 15meq/L More than 15meq/L NG Drainage Diuretics Alkalosis Mg depletion

Treatment of hypokalemia The goal of therapy: Is to remove the patient from immediate danger and not necessarily to correct the entire K deficit. Firstly concern : Any condition that promotes transcellular K shift.

Potassium replacement Oral replacement with KcL solution is generally safe(60-80 meq/d) IV replacement :(Remember ) Serious cardiac manifestation. Peripheral line not exceed 8 meq/h. More than 8meq/h, centeral line is indicated. Dextrose containing solution should be avoided. ECG monitoring is mandatory in high rate infusion.

Potassium replacement Solutions Potassium chloride and potassium phosphate Kcl: is available in 2meq/mL (5ml) is of choice with metabolic alkalosis as it corrects chloride shifts. Osmolality = 4000 mosm/kgH2O K phosphate: is of choice with coexisting hypophatemia (e.g DKA)

Potassium replacement Deficit =(3.5 - acutal serum K ) x 0.4 BW Maintenence = 1 meq / kg BW / day

Potassium replacement Infusion rate (pripheral line) Not exceed 8 meq / h Infusion rate (centeral line) Standard method = 20 meq KcL in 100 ml saline/h Maximum rate (serum k less than 1.5 meq/L) We need peripheral line = 40 meq kcL / h = ( ½ BW meq/h)

Practical approach If K level <2 mEq/L, deficit= 0.4 x wt(normal – measured K) we can give up to 0.5 mEq/kg/hr. If K level reaches 2.5 mEq/L, slowly corrects K by giving 10 mEq/hr. Add the daily intake (1 mEq/kg)

It is advisable to give K salts into large but not central vein. Potassium products: IV preparations Oral: 15ml= 40 mEq (if conc. Of KCl in sol. is 10%) Natural sources: -Orange: one orange=300mg K one litre juice=2.8gm K -Bananas: one piece= 750mg K K therapy in pediatrics: 1-3mEq/kg/every 1mEq decrease in K level with max. 3mEq/kg/day

Response to the treatment At first The serum K may be slow to rise particularly if K losses are ongoing Full replacement usually takes few days. If there is refractory hypokalemia check magnessium level

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CONCLUSION Potassium has important role to vital body function . Plasma K concentration is a function of relationship between entry, the intercompartemental distribution and excretion of K. Hypokalemia : serum K less thd 3.5meq/L Cause : Decrease intake, Losses and Intercompartemental shift. Effects : Cardiovascular,Neuromuscular,renal,Hormonal and metabolic. Diagnosis . Treatment :Goals, replacement and response

Hyperkalemia

Hyperkalemia Plasma [K+] > 5.0 Hyperkalemia may be the result of disturbances in external balance (total body K+ excess) or in internal balance (shift of K+ from intracellular to extracellular compartments)

Hyperkalemia: Disorders of External Balance Excessive K+ intake Acute & chronic renal failure Pseudo hyperkalemia  Distal tubular flow Distal tubular dysfunction Mineralocorticoid deficiency

Fist clenching (local exercise effect) Pseudohyperkalemia Movement of K+ out of cells during or after blood drawing Hemolysis Fist clenching (local exercise effect) Marked leukocytosis

Hyperkalemia: Disorders of External Balance Excessive Potassium Intake Oral or Parenteral Intake K pencillin in high doses Stored blood

Hyperkalemia: Disorders of External Balance Decreased Renal Excretion Acute and Chronic Renal Failure Decreased Distal Tubular Flow Volume depletion Decreased effective arterial blood volume (CHF, cirrhosis) Drugs altering glomerular hemodynamics with a decrease in GFR (NSAIDs, ACE inhibitors, ARBs) Mineralocorticoid Deficiency Combined glucocorticoid and mineralocorticoid (adrenal insufficiency) Hyporeninemic hypoaldosteronism (diabetes mellitus) Drug-induced (ACE inhibitors, ARBs) Distal Tubular Dysfunction Disorders causing impaired renal tubular function with hyporesponsiveness to aldosterone (interstitial nephritis) Potassium-sparing diuretics (amiloride, triamterene, spironolactone)

Hyperkalemia: Disorders of Internal Balance Insulin deficiency 2-Adrenergic blockade Hypertonicity Acidemia Cell lysis

Clinical Manifestations of Hyperkalemia Clinical manifestations result primarily from the depolarization of resting cell membrane potential in myocytes and neurons Prolonged depolarization decreases membrane Na+ permeability through the inactivation of voltage-sensitive Na+ channels producing a reduction in membrane excitability Cardiac toxicity EKG changes Cardiac conduction defects Arrhythmias Neuromuscular changes Ascending weakness, ileus

EKG Manifestations of Hyperkalemia Wide QRS Complex Shortened QT Interval Prolonged PR Interval Further Widening of QRS Complex Absent P - Wave Sine Wave Morphology (e.g. Ventricular Tachycardia) Peaked T wave Normal Increasing Serum K +

Medical Treatment of Hyperkalemia Membrane Stabilization IV calcium Internal Redistribution IV insulin (+ glucose) -adrenergic agonist (albuterol inhaled) Enhanced Elimination Kayexalate (sodium polystyrene sulfonate) ion exchange resin Loop diuretic Hemodialysis

Practical approach Mild cases: K<6.5mEq/L→causal management Moderate cases: K=6.5-8mEq/L: -glucose infusion. -glucose insulin infusion. -NaHCO3 Severe cases: K>8mEq/L→calcium injection

Emergency measures: -Dextrose 10%: 200-500ml over 30min. 500-1000ml over the next few hours. -Dextrose/insulin infusion Insulin: 0.1U/kg then 1U/kg/hr (add minimum 2-3 glucose/U insulin). Onset of effect is 1-5 min. -NaHCO3: 150mEq over several minutes ?increased pH causes K shift into cells.

Definitive measures: Key oxalate (Na polysterene) -Oral: 15-30g 2-4 times/day + sorbitol 20-25% (50ml/15gm resin) The resin induces diarrhea and leads to K loss. -Retention enema: 50gm in 200ml sorbitol 25%. Every gm resin combines with 1mEq K in GIT. Dialysis : in cases of RF.

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Potassium Disorders Normal homeostasis Hypokalemia Hyperkalemia Etiologic factors Algorithm for diagnosis Hyperkalemia Potassium Disorders