Hypokalaemia

1. Hypokalaemia By Dr Nihal Abosaif Consultant acute physician UHCW

2. Outline • Physiology of K+ transport • Factors modifying transcellular K+ distribution • Causes of Hypokalaemia • Diseases associated with it • Management of Hypokalaemia

3. Introduction : Potassium • Most abundant cation in human body • Regulates intracellular enzyme function and helps to determine neuromuscular & cardiovascular tissue excitability. • 90 % of total body K+ : Intracellular ( predominantly in muscle ) • 10 % : Extracellular fluid • < 1 % : Plasma

4. Introduction : Potassium • Ratio of extracellular K+ to Intracellular K+ : determines the membrane potential • The acuity of changes in serum potassium concentration & membrane potential determines clinical symptoms and underlying signs • Plasma concentration varies from 3.5 to 5.3 mmol/l

5. Physiology Of Potassium Homeostasis • K+ uptake into cells : actively driven by Na+/K+/ATPase • Leak back into ECF : opposed by electrical gradient

7. Factors modifying transcellular K+ distribution • Acid base status • Pancreatic hormones : insulin , glucagon • Catecholamines • Aldosterone • Plasma Osmolality • Exercise • Cellular K+ content

8. Acid Base Status • Alkalosis promotes K+ uptake by cells • Acidosis diminishes K+ uptake by cells • Acute respiratory alkalosis, in contrast increase plasma K+ by 0.2 mmol/l per 0.1 pH unit due to increased adrenergic activity

9. Pancreatic Hormones • Insulin stimulates cellular uptake of K+ by activating Na+/K+/ATPase ( decreasing plasma K+ ) • Insulin affects K+ transport independently of glucose uptake • Glucagon increase plasma K+ independently of changes in plasma glucose / insulin

10. Catecholamines • Beta 2 adrenergic activity – hypokalaemia • Alpha adrenergic antagonists – hypokalaemia

11. Aldosterone • Invitro studies • Aldosterone stimulates Na+/K+/ATPase and thereby activating Na + influx

12. Osmolality • Hyperosmolality ( Mannitol infusion / hyperglycemia in DM ) : increase plasma K+ • Each 10 mOsm / Kg rise in plasma osmolality, increases plasma K+ by 0.6 mmol/l

13. Exercise • Recurrent contraction increases K+ egress from muscle • Modest exercise : high K+ in ECF in local environment produces vasodilatation & thereby increased regional blood flow • Severe exercise : increase plasma K+ modestly • Physical training increases Na+/K+/ATPase activity in skeletal muscle which helps skeletal muscle to take up K+ again

14. K+ Balance • Kidney is dominant in sustaining K+ balance • >90 % K+ : excreted in urine • Remainder through faeces • Decrease in GFR, K+ excretion via faeces increased • GI Loss : K+ secretion by proximal & distal colon

15. Renal Handling of K+ • Glomerulus: freely filtered • PCT, TAL, Loop of Henle : reabsorbed

16. Hypokalemia • Defined as plasma concentration of K+ < 3.5 mEq/L • Mild Hypokalemia : 3.0 – 3.5 mEq/L : asymptomatic • Hypokalemia < 3.0 mEq/L : symptomatic • Clinical manifestations of hypokalemia vary greatly between individual patients & their severity depends on degree of hypokalemia

17. Diagnosis • Clinical features • Investigations

18. Clinical Features • Mild hypokalemia : generally asymptomatic Increased risk of mortality for pts with cardiovascular disease – trigger ventricular tachycardia / ventricular fibrillation (decrease K+ : d/t sympathetic stimulation) Digitalis induced arrhythmias – can occur with normal drug levels if hypokalemia is present Diuretic induced hypokalemia & hypomagnesemia must be avoided in pts on drugs that prolong QT interval : as it predisposes to polymorphic VT / Torsade de pointes • Hypokalemia < 3 mEq/L : Symptomatic

19. Cardiac • Digitalis Intoxication : ventricular extrasystoles ventricular tachycardia ventricular fibrillation partial-complete AV block bradycardia atrial flutter atrial fibrillation • Ventricular arrhythmias : tachycardia / fibrillation

20. Neuro-muscular • Fatigue • Myalgia • Muscular weakness involving lower limbs Severe Hypokalemia : • Paralysis ( extremities ) • Weakness of respiratory muscles ( dyspnea ) • Rhabdomyolysis (exercise induced)

21. Gastro-intestinal • Constipation • Paralytic ileus

22. Renal • Chronic interstitial nephritis due to functional decrease in renal blood flow – decreased GFR • Chronic renal failure • Renal Cysts

23. Fluid – Electrolyte • Polyuria ( nephrogenic diabetes insipidus ) • Polydipsia ( nephrogenic diabetes insipidus ) • Increased ammonia production ( intracellular acidosis ) precipitate hepatic coma in pts with advanced liver ds • Edema • Chloride wasting • Metabolic alkalosis • Hypercalciuria • Phosphaturia

24. Endocrine • Glucose intolerance ( decreased insulin secretion ) • Growth retardation ( Reduced Growth hormone receptors, Reduced IGF-1 ) • Hypertension ( increased renin secretion )

25. Basic Investigations • ECG : Initially : flattening of t wave depression of ST Segment development of prominent u waves Severe hypokalemia : increased amplitude of p wave increased QRS duration • S.Potassium

26. Investigations – Causes • Urinary K+ • TTKG • Urinary Chloride • CBC • Peripheral Smear • ABG • Echocardiogram • Cardiac Enzymes • Serum aldosterone • Serum renin • USG Abdomen • CT / MRI Abdomen • FBS / PPBS / Urine Ketones • TSH / free T3 / free T4 • Colonoscopy / OGDscopy

27. Causes of hypokalaemia • Decreased net intake • Shift into cells • Increased net loss

30. Spurious Hypokalemia • Occurs in patients with extreme leukocytosis eg : in myeloproliferative disorders • Invitro WBC uptake potassium within the test tube

31. Decreased Intake or increased loss • Starvation • Clay ingestion ( binds to dietary K+ & Iron ) • Diarrhoea and vomiting

32. Transcellular shifts • Acid – Base Status : Metabolic Alkalosis • Hormonal : Increased Insulin Increased Beta 2 Adrenergic activity • Drugs : Beta 2 agonists Theophylline Barium Intoxication Chloroquine Calcium Channel Blockers

33. Transcellular shift • Catecholamine release associated with : • Asthma • COPD – exacerbations • Heart failure • Myocardial infarction / angina • Drug withdrawal syndrome – alcohol / narcotics / barbiturates

34. Transcellular shift • Insulin administration – for treatment of DKA • Refeeding Syndrome • Hypokalemic Periodic Paralysis • Thyrotoxic Periodic Paralysis • Treatment of anemia : Vit B12 / Folic acid deficiency • Use of GM – CSF in patients with Neutropenia

35. Renal Vs Extra renal loss • Urinary K+: > 20 mEq/L – Renal loss • Urinary K + : < 20 mEq/L – Extrarenal loss • TTKG : Transtubular Potassium Gradient ( Urine K+ / Plasma K+ ) ( Urine Osm / Plasma Osm ) • TTKG : Renal loss : > 4 Extra renal loss : < 4

36. Algorithm for diagnosis of Extra Renal Loss

37. Renal Loss

38. Renal Loss + Metabolic Alkalosis

39. Renal loss +Urine Cl > 20 mEq/L

40. Renal loss - Drugs • Amphotericin B : tubular damage increased excretion of K+ • Aminoglycosides : renal wasting of K+ • Thiazides, Furosemide, Acetazolamide : renal loss K+ • Cisplatin • HYPOMAGNESEMIA : Significant renal K+ wasting

41. Management of Hypokalaemia • If mild asymptomatic • Oral KCl • If severe or symptomatic hypokalemia • IV KCl supplement

42. IV infusion rate for severe or symptomatic hypokalemia .

43. THANK YOU