Hypokalemia - Approach and Management

Potassium - facts, Renal Handling.
Hypokalemia - Definition, causes, Approach to hypokalemia and its Management.

1. HYPOKALEMIA Dr. Adhiya.N.S.S M.D GENERAL MEDICINE First Year Post Graduate

2. POTASSIUM It is the most abundant cation in the Human Body. Total Body stores are approximately 3000 to 4000 mEq . It is a major intracellular cation . Intracellular K concentration : 130 -140 mEq /L Extracellular K concentration : 4 – 5 mEq /L It is found primarily in the muscles (70%), and to a lesser extent in bone, red blood cells, liver and skin.

3. FUNCTIONS OF POTASSIUM The normal ratio between extracellular and intracellular potassium concentration is important for the maintenance of the resting membrane potential and neuromuscular functioning. Intracellular Potassium: Cell growth and maintenance of cell volume DNA and Protein synthesis Acid –Base balance

4. POTASSIUM HOMEOSTASIS

5. HYPOKALEMIA It is an electrolyte disorder characterized by Serum Potassium concentrations less than 3.5 mEq /L. (Normal Range: 3.5 – 5.0 mEq /L). It is present in upto 20% of hospitalized patients and is associated with a ten-fold increase in in-hospital mortality. It may be asymptomatic or have dangerous complications such as arrthymias or paralysis.

6. CLINICAL MANIFESTATIONS OF HYPOKALEMIA CARDIOVASCULAR: Increased Blood Pressure. Increased sensitivity to Arrhythmias. Increased risk of Digitoxicity . SKELETAL MUSCLES: Weakness, Flaccid muscle paralysis, Rhabdomyolysis . SMOOTH MUSCLE: Constipation, Ileus and rarely bladder dysfunction. ENDOCRINE: Worsening of glucose control in diabetics.

7. RENAL: Polyurea due to Nephrogenic Diabetes Insipidus . It may lead to formation of Renal cysts. It may precipitate or worsen hepatic encephalopathy due to increased renal ammonia production. Increased ammonia production might also contribute to the development of metabolic alkalosis. Conversely metabolic alkalosis may increase renal potassium excretion and cause hypokalemia It may also cause Renal Failure as potassium depletion causes tubulointerstitial fibrosis which is characterised by vacuolization of PCT.

8. ECG CHANGES IN HYPOKALEMIA Flattening of T waves Prominent U waves Biphasic T waves (Dip and Rise pattern) ST depression QT prolongation/ QU prolongation (T-U fusion wave) P R prolongation Wide QRS Ventricular arrhythmias if associated with hypomagnesaemia

9. POTASSIUM LEVELS ECG CHANGES 3.5 – 4.0 NORMAL < 3.5 FLATTENING OF T WAVES PROMINENT U WAVES PROLONGED QT/ QU INTERVAL < 3 SAGGING/ DEPRESSION OF ST SEGMENT < 2.5 QRS WIDENING PR PROLONGATION

10. CAUSES OF HYPOKALEMIA PSEUDOHYPOKALEMIA: After phlebotomy, if the blood is stored for prolonged periods at room temperature, if large number of leucocytes are present, they might take up the potassium present in the serum. The most common cause is acute leukemia . Rapid separation of plasma and storage at 4 degree celcius is used to confirm this diagnosis.

11. CAUSES (Cont...) DECREASED INTAKE: Starvation or Dietary Deficiency Clay ingestion REDISTRIBUTION INTO CELLS: Acid-Base: Metabolic Alkalosis Hormonal: Insulin Increased Beta 2 adrenergic activity – Post MI or Head Injury Beta 2 adrenergic agonists – Bronchodilators and Tocolytics Alpha adrenergic agonists Thyrotoxic Periodic Paralysis Downstream stimulation of Na/K – ATPase : Theophylline , Caffeine

12. CAUSES (Cont...) C. Anabolic state: Vitamin B12 or Folic Acid administration leading to increased Red Blood Cell production. Granulocyte-Macrophage colony stimulating factor leading to White Blood Cell production. Total Parenteral Nutrition. D. Familial Hypokalemic Periodic Paralysis E. Hypothermia F. Barium Toxicity: Systemic inhibition of Potassium leak channels.

13. CAUSES (Cont...) NON-RENAL LOSS: Gastrointestinal loss: Upper GI loss – Vomiting, Nasogastric aspiration: Associated with metabolic alkalosis. Lower GI loss – Diarrhoea, Laxative abuse, Villous adenoma, Bowel obstruction/ fistula, Ureterosigmoidostomy Integumentary loss: Sweat – In extremes of physical exertion.

14. CAUSES (Cont...) RENAL LOSS: Increased Tubular Flow: Diuretics Osmotic diuresis Salt-wasting Nephropathies Increased secretion of Potassium: Mineralocorticoid excess: Primary hyperaldosteronism Secondary hyperaldosteronism Genetic hyperaldosteronism Cushing’s Syndrome Bartter’s Syndrome Gitelman’s Syndrome

15. RENAL LOSS: (Cont...) Apparent mineralocorticoid excess: Genetic deficiency of 11 Beta dehydrogenase 2 Inhibition of 11 Beta hydrogenase 2 ( Carbenoxolone , licorice ) Liddle’s syndrome Distal delivery of non reabsorbed anions: Renal Tubular Acidosis Diabetic Ketoacidosis Penicillin derivatives Toluene Abuse (Glue sniffing) Magnesium deficiency

16. APPROACH TO HYPOKALEMIA

17. TRANSTUBULAR POTASSIUM GRADIENT TTKG is the ratio of potassium concentration in the lumen of cortical collecting duct to that in the peritubular capillaries. TTKG = Urine Potassium x Serum osmolality / Serum Potassium x Urine osmolality During hypokalemia , TTKG should fall below 3 indicating an appropriately reduced urinary excretion of potassium. TTKG greater than 4 indicates renal potassium loss due to increased distal potassium secretion.

18. TREATMENT OF HYPOKALEMIA The goals of therapy are To prevent life-threatening or serious consequences To replace the potassium deficit To correct the underlying cause Urgency of therapy depends on severity of hypokalemia , rate of decline and associated clinical factors. Serum potassium drops by 0.27 mmol for every 100 mmol reduction in body stores.

19. REPLACEMENT OF POTASSIUM DEFICIT Oral correction is the preferred route of treatment. Potassium Chloride is the mainstay of therapy because increase in extracellular potassium is fast compared with other salts. Potassium phosphate is appropriate in patients with combined hypokalemia and hypophosphatemia . Potassium citrate should be considered in patients with concomitant metabolic acidosis.

20. REPLACEMENT OF POTASSIUM DEFICIT (Continued..) IV administration should be limited to patients unable to use enteral route or in the setting of severe complications. IV KCl is preferred. It should be administered in saline solutions, rather than dextrose , because the dextrose induced increase in insulin can acutely exacerbate hypokalemia .

21. REPLACEMENT OF POTASSIUM DEFICIT (Continued..) The peripheral intravenous dose is 20-40 mEq /L. Higher concentrations can cause chemical phlebitis, irritation and sclerosis. If severe hypokalemia (<2.5 mEq /L) is present or if the patient is critically symptoatic , IV KCl should be administered through a central line at the rates of 10-20 mEq /hr. 1 ampule of KCl is equal to 10ml. 1 ml is equal to 2 mEq . So 1 ampule has 20 mEq . And 20 mEq increases potassium by 0.25 mEq /L.

22. REFERENCES HARRISON’S PRINCIPLES OF INTERNAL MEDICINE – 20 TH EDITION Comprehensive Clinical Nephrology by Richard J. Johnson Hypokalemia : a clinical update Efstratios Kardalas , Stavroula A Paschou ,   Panagiotis Anagnostis ,   Giovanna Muscogiuri ,   Gerasimos Siasos ,  and  Andromachi Vryonidou

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