Hypokalemia and Hyperkalemia Dr Madhukar Mittal Medical Endocrinology

Hypokalemia Spurious Extreme leukocytosis (WBC uptake of K+ in the test tube)

Decreased Total Body K+ Transcellular shift Stress induced catecholamine release Asthma, COPD exacerbation, CHF, MI/Angina, Drug withdrawal syndrome Drugs Insulin Theophylline, β2 agonists Anabolic state Vit B12 or Folate treatment GM-CSF TPN Hypokalemic periodic paralysis Decreased Total Body K+

3. Decreased Total Body K+ Renal Loss (urinary K+>20meq/l) Extra-renal Loss (urinary K+<20meq/l) Metabolic alkalosis Mineralocorticoid excess Primary aldosteronism Secondary aldosteronism ↑ mineralocorticoid (Non-aldosterone) action Normal/↓ BP, No edema, Secondary aldosteronism Bartter syndrome Gitelman syndrome Diuretic abuse Chronic vomiting Hypomagnesemia Metabolic acidosis DKA RTA type 1 & 2 Ureterosigmoidostomy Amphotericin B Acetozolamide Normal pH Decreased intake GI losses Metaboic acidosis Lower GI losses Diarrhea Laxative abuse Metabolic alkalosis Villous adenoma Congenital Cl- losing diarrhea Remote vomiting Remote diuretic use Variable pH Postobstructive diuresis Drugs Aminoglycosides Cisplatin

(urinary K+>20meq/l) Renal Loss (urinary K+>20meq/l) Metabolic alkalosis Mineralocorticoid excess Primary aldosteronism Secondary aldosteronism ↑ mineralocorticoid (Non-aldosterone) action Normal/↓ BP, No edema, Secondary aldosteronism Bartter syndrome Gitelman syndrome Diuretic abuse Chronic vomiting Hypomagnesemia Metabolic acidosis DKA RTA type 1 & 2 Ureterosigmoidostomy Amphotericin B Acetozolamide Normal pH Decreased intake GI losses

(urinary K+<20meq/l) Extra-renal Loss (urinary K+<20meq/l) Metaboic acidosis Lower GI losses Diarrhea Laxative abuse Metabolic alkalosis Villous adenoma Congenital Cl- losing diarrhea Remote vomiting Remote diuretic use Variable pH Postobstructive diuresis Drugs Aminoglycosides Cisplatin

↑Aldosterone, ↓PRA (Primary Aldosteronism) Adrenal adenoma (Conn syndrome) Idiopathic hyperplasia Adrenal carcinoma Glucocorticoid remediable aldosteronism (GRA)

Hypermineralocorticolism/Aldosteronism (Metabolic alkalosis, Hypokalemia, ↑BP) ↑↑Aldosterone, ↑PRA (Secondary Aldosteronism) Edema states (Cirrhosis, CHF, Nephrosis) Pregnancy (Normal physiologic response) ↑Renin d/t ↓Renal blood flow Renal artery stenosis Accelerated Hypertension (renal vasoconstriction) Malignant hypertension (arteriolar nephrosclerosis) Primary reninism Renin producing tumors ↓/N BP, No edema Bartter syndrome Gitelman syndrome Chronic vomiting Diuretic abuse Hypomagnesemia Hypertensive States BCD GH

Hypermineralocorticolism/Aldosteronism (Metabolic alkalosis, Hypokalemia, ↑BP) ↓/N Aldosterone, ↓PRA (↑ Mineralocorticoid action) Liddle syndrome Cushing syndrome AME (apparent mineralocorticoid excess syndrome) Licorice/Carbenoxolone ingestion (Glycyrrhizinic acid Ɵ 11-βHSD II enzyme) CAH – 11β hydroxylase deficiency DOC (deoxycorticosterone) secreting tumour LAL CD

Hypermineralocorticolism/Aldosteronism (Metabolic alkalosis, ↓ K+, ↓/N BP) Bartter syndrome Hypercalciuria Gitelman syndrome ↓Urinary Ca, ↓ serum Mg Diuretic abuse Hypomagnesemia Chronic vomiting Urine Cl- <10meq/l Urine Cl- >20meq/l

CVS - ECG Flattening or inversion of T wave with ST depression Prominent U waves Prolonged QT (QU) interval + prolonged PR interval, wide QRS complex Atrial and ventricular arrhythmias Predisposition to digitalis toxicity

Clinical NeuroMs Endocrine Renal Weakness, flaccid paralysis Cramps, tetany, rhabdomyolysis Ileus, constipation, urinary retention Endocrine Glucose intolerance Growth retardation, ↓ aldosterone Renal ↓ renal blood flow, ↓ GFR Nephrogenic diabetes insipidus Increased ammoniagenesis (hepatic encephalopathy) Chloride wasting/metabolic alkalosis

Treatment Agent Max concentration Infusing solution Rate of infusion KCl Pot bicarbonate and citrate for hypokalemia associated with chronic diarrhea, RTA Max concentration <40 mmol/l via peripheral vein <60 mmol/l via central vein Infusing solution NS Mannitol Rate of infusion <20mmol/hr unless paralysis, malignant ventr arrhythmias

Treatment Montoring Hypokalemic periodic paralysis Clinical – NeuroMs ECG Plasma K conc. Hypokalemic periodic paralysis Ca channel disorder Oral KCl 0.2-0.4 mmol/Kg every 15-30 min IV KCL in mannitol Long term – Actazolamide 125-1000 mg/d, Triamterene 25-100 mg/d, Spironolactone 25-100 mg/d, Dichlorphenamide 50-200 mg/d

Hyperkalemia Spurious (Pseudo) Prolonged use of tourniquet Ischemic blood draws RBC hemolysis in test tubes Marked thrombocytosis or leukocytosis

Transcellular shift Chronic Hyperkalemia Metabolic acidosis Drugs Insulin deficiency and hypertonicity β blockers Tissue breakdown Rhabdomyolysis Tumor lysis syndrome Intravascular hemolysis Hyperkalemic periodic paralysis Drug toxicity Digitalis succinylchloline Chronic Hyperkalemia

3. Chronic Hyperkalemia (Metabolic acidosis, Hypokalemia) ↓Aldosterone, ↑PRA (Hypoaldosteronism) Primary adrenal insufficiency Aldosterone bisynthetic defect Mutation in aldosterone synthase gene (cyp 11B2) CAH – Lipoid, 3β-HSD def, 21-OH-lase deficiency Heparin ACE Ɵ, ARBs (selective unresposivensess to angiotensin II) ↓Aldosterone, ↓PRA (Hyporeninemic Hypoaldosteronism) NSAIDS Chronic TIN, Diabetic Nephropathy, Mild renal failure

3. Chronic Hyperkalemia ↓Aldosterone, ↓PRA, ↑BP, (Cl- shunt/reabsorption in distal tubule) PHA-II (Gordon’s syndrome) Cyclosporine Distal Type 4 RTA ↑Aldo, ↑PRA, ↓BP (Mineralocorticoid Resistant Hyperkalemia), Impaired distal Na+ reabsorption PHA-I Potassium sparing diuretics - Spironolactone, Eplerenone, Triamterene, Amiloride Trimethoprim Pentamidine

↓Aldosterone, ↓PRA (Hypoaldosteronism) NSAIDS Chronic TIN Mild renal failure Cl- shunt/reabsorption in distal tubule (↑BP) Cyclosporine Type 4 RTA Gordon syndrome (PHA-II)

↑Aldosterone, ↑PRA (Mineralocorticoid Resistant Hyperkalemia) PHA-I Potassium sparing diuretics Spironolactone, Eplerenone Triamterene, Amiloride Trimethoprim Pentamidine ↓BP Impaired distal Na+ reabsorption

CVS - ECG Tall peaked (tented) T waves (earliest change) Short QT interval Wide QRS, PR interval prolongs → 20 or 30 AV block ↓ P wave amplitude → complete loss of P waves with associated junctional rhythm QRS widens → sine wave (ventr. flutter-like) pattern Eventual asystole

Treatment Restrict K intake to <40 mmol/day Stop K supplements Stop K sparing diuretics

Treatment Ca gluconate (10%) 10 ml over 1 -3 min IV Repeat if no change in ECG after 5-10 min 10-20 U regular insulin + 25-50g glucose IVI NaHCO3 3 amp (50-150mmol) in 1L of 5%D Nebulized β2agonist (albuterol 20mg in 4ml NS)

Treatment Diuretics – furosemide 60-80 mg/day Resins (sodium polysterene sulfonate) 25-50g in 100ml of 20% sorbitol Retention enema 50g in 50ml of 70% sorbitol in 150ml tap water Dialysis For patients with renal failure Severe life-threatening hyperkalemia unresponsive to conservative treatment Hemodialysis – most rapid and effective way Peritoneal dialysis – only 15-20% as effective as hemodialysis

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