Potassium disorders-hypokalemia and hyperkalemia

Dr RAVEENA S, INTERN, DEPARTMENT OF GENERAL MEDICINE, AZEEZIA MEDICAL COLLEGE, KOLLAM

1. POTASSIUM DISORDERS RAVEENA SUDHAKARAN

2. Potassium is a major intracellular cation Total body k+ in a normal adult – 3000 – 4000mEq 98% intracellular , 2% in ECF Normal homeostatis mechanisms maintain serum K level 3-5 – 5.0 mEq /L Primary mechanism in maintaining this balance are buffering of ECF potassium against a large ICF potassium pool ( via the Na – K pump) Na – K ATPase pump actively transports Na + out of cell and K+ into cell ina 3:2 ratio.

3. Renal excretion – major route of excess K+ elimination Approx 90 % K+ excretion occur in urine. Less than 10% excreted through sweat or stool. In kidney K+ excretion occur mostly in principal cells of cortical collecting duct. Urinary excretion depends on 1. luminal Na+ delivery to DCT and CCD 2.Effect of aldosterone and other adrenal corticosteroids with mineralocorticoid activity

4. HYPOKALEMIA plasma K+ concentration of < 3.5mM

5. CAUSES I. Decreased intake Starvation Clay ingestion II. Redistribution into cells A.Metabolic alkalosis B. Hormonal Insulin Increased β2-adrenergic sympathetic activity: post–myocardial infarction, head injury β2-Adrenergic agonists—bronchodilators, tocolytics α-Adrenergic antagonists Hyperthyroidism - Thyrotoxic periodic paralysis ( hypokalemic paralysis Downstream stimulation of Na+/K+-ATPase: theophylline, caffeine

6. C. Anabolic state Vitamin B12 or folic acid administration (red blood cell production) Granulocyte-macrophage colony-stimulating factor (white blood cell production Total parenteral nutrition D. Other Pseudohypokalemia Hypothermia Familial hypokalemic periodic paralysis Barium toxicity: systemic inhibition of “leak” K+ channels

7. III. Increased loss Nonrenal Gastrointestinal loss (diarrhea) Integumentary loss (sweat) B. Renal Increased distal flow and distal Na+ delivery: diuretics, osmotic diuresis, salt-wasting nephropathies Increased secretion of potassium a. Mineralocorticoid excess: hyperaldosteronism , Cushing’s syndrome b. Apparent mineralocorticoid excess: genetic deficiency of 11β-dehydrogenase-2 , inhibition of 11β-dehydrogenase-2 c. Distal delivery of nonreabsorbed anions - vomiting, nasogastric suction, proximal renal tubular acidosis, diabetic ketoacidosis Magnesium deficiency

8. CILICAL FEATURES Prominent effects on cardiac, skeletal, and intestinal muscle cells Major risk factor for both ventricular and atrial arrhythmias. ECG changes broad flat T waves ST depression QT prolongation serum K+ is <2.7 mmol/L. Hyperpolarization of skeletal muscle - weakness and even paralysis Intestinal ileus, constipation , bladder dysfunction

9. The functional effects of hypokalemia on the kidney Na+-Cl– and HCO3– retention  metabolic alkalosis polyuria, phosphaturia, hypocitraturia activation of renal ammoniagenesis . Structural changes in the kidney - injury to proximal tubular cells, interstitial nephritis, and renal cysts Implicated in the pathophysiology and progression of hypertension, heart failure, and stroke

10. DIAGNOSTIC APPROACH History - medications (laxatives, diuretics, antibiotics), diet and dietary habits or symptoms that suggest a particular cause (e.g., periodic weakness, diarrhea). Physical examination - blood pressure, volume status, and signs suggestive of specific hypokalemic disorders (hyperthyroidism and Cushing’s syndrome). Initial laboratory evaluation electrolytes, BUN, creatinine, serum osmolality, Mg2+, Ca2+ complete blood count urinary pH, osmolality, creatinine, and electrolytes

11. TREATMENT GOALS Prevent life-threatening and/or serious chronic consequence Replace the associated K+ deficit Correct the underlying cause The urgency of therapy depends on the severity of hypokalemia , associated clinical factors (e.g., cardiac disease, digoxin therapy), and the rate of decline in serum K+. Excessive activity of the sympathetic nervous system- high-dose propranolol (3 mg/kg) should be considered

12. Oral replacement with K+-Cl– mainstay of therapy Potassium phosphate, oral or IV - combined hypokalemia and hypophosphatemia Potassium bicarbonate or potassium citrate - metabolic acidosis.

13. Intravenous K+-Cl– should always be administered in saline solutions, rather than dextrose, because the dextrose-induced increase in insulin can acutely exacerbate hypokalemia . Intravenous dose is usually 20–40 mmol of K+-Cl– per liter higher concentrations - localized pain from chemical phlebitis, irritation, and sclerosis. Severe and/or critically symptomatic - intravenous K+-Cl– through central vein with cardiac monitoring in an intensive care setting, at rates of 10–20 mmol/h. Femoral veins are preferable, because infusion through internal jugular or subclavian central lines can acutely increase the local concentration of K+ and affect cardiac conduction

14. Strategies to minimize K+ losses minimizing the dose of non-K+-sparing diuretics restricting Na+ intake clinically appropriate combinations of non-K+-sparing and K+-sparing medications (e.g., loop diuretics with ACE inhibitors).

15. HYPERKALEMIA plasma potassium level of >5.5 mEq /L Severe hyperkalemia - serum potassium Levels are >6.0meq/L

16. CAUSES PSEUDOHYPERKALEMIA Artifactual increase in serum potassium during or after venipuncture Mainly occur due to marked increase in muscle activity during venipuncture Marked increase in cellular elements (thrombocytosis, erythrocytosis, leukocytosis) Cooling of blood following venipuncture genetic subtypes caused by – increases in potassium permeability of erythrocytes

17. INTRA- TO EXTRACELLULAR SHIFT Acidosis – cellular uptake of H+ Hyperosmolality - hypertonic dextrose, mannitol – solvent drag effect β2-Adrenergic antagonists ( noncardioselective agents) suppresses catecholamines stimulated renin release – in turn aldosterone synthesis Digoxin and related glycosides – inhibits Na – K ATPase Hyperkalemic periodic paralysis Lysine, arginine, and ε-aminocaproic acid (structurally similar, positively charged) Succinylcholine – depolarizes muscle cells  efflux of K+ through AChRs C/I - thermal trauma, neuromuscular injury, disuse atrophy, mucositis, or prolonged immobilization Rhabdomyolysis

18. INADEQUATE EXCRETION A. Inhibition of the renin-angiotensin-aldosterone axis ↑ risk of hyperkalemia when used in combination Angiotensin-converting enzyme (ACE) inhibitors Renin inhibitors; aliskiren Angiotensin receptor blockers (ARBs) Blockade of the mineralocorticoid receptor: spironolactone, eplerenone Blockade of the epithelial sodium channel (ENaC): amiloride, triamterene, trimethoprim, pentamidine B. Decreased distal delivery Congestive heart failure Volume depletion

19. C. Hyporeninemic hypoaldosteronism Tubulointerstitial diseases: SLE , sickle cell anemia, obstructive uropathy Diabetes, diabetic nephropathy Drugs: NSAIDs, COX2 inhibitors, β-blockers, cyclosporine, tacrolimus Chronic kidney disease, advanced age Pseudohypoaldosteronism type II D. Renal resistance to mineralocorticoid Tubulointerstitial diseases: SLE, amyloidosis, sickle cell anemia, obstructive uropathy, post–acute tubular necrosis Hereditary: pseudohypoaldosteronism type I; defects in the mineralocorticoid receptor or the epithelial sodium channel (ENaC)

20. E. Advanced renal insufficiency Chronic kidney disease End-stage renal disease Acute oliguric kidney injury F. Primary adrenal insufficiency Autoimmune: Addison’s disease Infectious: HIV, cytomegalovirus, tuberculosis, disseminated fungal infection Infiltrative: amyloidosis, malignancy, metastatic cancer Drug-associated: heparin, low-molecular-weight heparin Hereditary: adrenal hypoplasia congenita, aldosterone synthase deficiency

21. CLINICAL FEATURES Mostly asymptomatic If present – are non specific and predominantly related to muscular or cardiac functions Most common – weakness and fatigue CARDIAC ARRHYTHMIAS – sinus bradycardia, ventricular tachycardia, ventricular fibrillation, asystole

22. ECG CHANGES S.Potassium ECG 6-7 Tall peaked T waves 7-8 Prolonged PR interval Depressed ST segment Flattened P wave 8-9 Prolonged QRS >9 Sine wave pattern

23. DIAGNOSTIC APPROACH History on medications, diet, risk factors for kidney failure, reduction in urine output, blood pressure, volume status BUN , creatinine, serum osmolality Serum electrolytes – Mg, Ca Urine potassium, sodium , osmolality Complete blood count ECG

24. TREATMENT 3 main approaches to the treatment of hyperkalemia : Immediate antagonism of the cardiac effects of hyperkalemia Rapid reduction in plasma K+ concentration by redistribution into cells Removing excess potassium from the body

25. Immediate antagonism of the cardiac effects of hyperkalemia 10 mL of 10% calcium gluconate, infused intravenously over 2–3 min with cardiac monitoring The effect of infusion strats after 1to 3 min and lasts for 30 to 60 min Dose should be repeated if there is no change in ECG findings and they recur after intial improvement

26. Rapid reduction in plasma K+ concentration by redistribution into cells . Insulin lowers plasma K+ concentration by shifting K+in to cell 10 units of intravenous regular insulin followed by 50ml of 50% dextrose Effect begin in 10-20 minutes, peak in 30-60 minutes, last for 4-6h In hyperkalemic patients with glucose concentrations>200mg/dl insulin should be given without glucose with blood glucose monitering

27. Salbutamol nebulization 10-20 mg Adjuvant therapy Act in 30 mins, last for 2-4 hrs

28. Removal of potassium cation exchange resins, Diuretics, and/or Hemodialysis. Cation Exchange Resins sodium polystyrene sulfonate (SPS) exchanges Na+ for K+ in the gastrointestinal tract and increases the fecal excretion of K+ Dose of SPS is 15–30 g of powder,given in a premade suspension with 33% sorbitol. The effect of SPS on plasma K+ concentration is slow; the full effect may take up to 24 h and usually requires repeated doses every 4–6 h. Interstitial necrosis – complication

29. Intravenous saline - beneficial in hypovolemic patients with oliguria with decresed delivery of Na to distal collecting ducts Loop and Thiazide diuretics can be used to reduce plasma K+ concentration in volume- replete or hypervolemic patients with sufficient renal function for diuretic response usually combined with iv saline or isotonic bicarbonate to achieve or maintain euvolemia

30. Hemodialysis most effective and reliable method The amount of K+ removed during hemodialysis depends on - The relative distribution of K+ between ICF and ECF, The type and surface area of the dialyzer used, dialysate and blood flow rates, dialysate flow rate, dialysis duration, and the plasma-to- dialysate K+ gradient.

31. THANK YOU