1. Disorders of potassium balance Zhao Chenghai Pathophysiology

2. Outline Potassium balance Disorders of potassium balance –Hypokalemia –Hyperkalemia

3. Potassium balance

4. Distribution of potassium Gains and losses of potassium Mechanisms of regulation Functions of potassium Potassium balance

5. Distribution of potassium The intracellular concentration of potassium ranges from 140 to 150 mmol/L. The extracellular concentration of potassium (3.5-5.0mmol/L) is considerable less.

6. Gains and losses Food is the main source of potassium intake. The kidneys are the main source of potassium elimination.

7. Mechanisms of regulation Renal regulation Transcellular shift between the intracellular and extracellular compartments

8. Renal regulation Secretion of potassium by distal and collecting tubules. Aldosterone --- a sodium-potassium exchange system. Sodium is transported back into blood. Potassium is secreted into tubular filtrate. Mineralocorticoid hormone Plasma potassium levels control aldosterone secretion by adrenal gland.

9. Transcellular shifts Sodium-potassium ATPase –Both insulin and epinephrine increase the activity of sodium-potassium pump. (An increase in potassium level stimulates insulin release. --- a feedback mechanism) Potassium channels –ECF osmolality↑→H 2 O leaves cell→ ICF K + ↑→ K + moves out of cell through K + channels →ECF K + –Exercise Potassium-hydrogen exchange to maintain electrical neutrality –In acidosis –In alkalosis

10. Functions of potassium Maintain the osmotic integrity of cells –Osmotic pressure in ICF Maintain acid-base balance –Through potassium-hydrogen exchange Contribute to the reactions that take place in cells –Transform carbohydrates into energy –Convert amino acid to protein –Change glucose into glycogen Play a critical role in the excitability of skeletal, cardiac, and smooth muscle.

11. Resting membrane potential (RMP) RMP≈-59.5lg[K + ] i /[K + ] e Excitability of muscle cells can be affected by the distance between RMP and threshold potential.

12. Hypokalemia Hypokalemia refers to a decrease in plasma potassium level below 3.5 mmol/L.

13. Causes of hypokalemia Inadequate intake –inability to obtain or ingest food –Diet deficient in potassium Excessive renal, gastrointestinal and skin losses –Diuretic therapy (thiazide and loop diuretics) –Increased aldosterone level (primary aldosteronism, stress-cortisol) –burn, sweating increase, vomiting and diarrhea Transcellular shift –Administration of insulin (to treat diabetic ketoacidosis) –β -adrenergic agonist----albuterol (bronchodilator) –Alkalosis

14. Manifestations of hypokalemia Neuromuscular manifestations –Muscle flabbiness, weakness and fatigue –Muscle cramps and tenderness –Paresthesia and paralysis Impaired kidney’s ability to concentrate the urine –polyuria, urine with low osmolality, polydipsia (ECF osmolality↑) Gastrointestinal manifestations –Anorexia, nausea, vomitting, –Constipation, abdominal distension, paralytic ileus Cardiovascular manifestations –Arrhythmias, increased sensitivity to digitalis toxicity Metabolic alkalosis

15. ECG changes in hypokalemia Depression of the ST segment Flattening of the T wave Appearance of a prominent U wave Prolongation of PR interval

16. Treatment of hypokalemia Increasing the intake of foods high in potassium content Oral potassium supplements Giving potassium intravenously when rapid replacement is needed. –Only if the renal function is adequate

17. Hyperkalemia Hyperkalemia refers to an increase in plasma levels of potassium in excess of 5.0mmol/L.

18. Causes of hyperkalemia Decreased renal elimination –Decreased renal function-renal failure –Treatment with potassium-sparing diuretics –Decreased aldosterone level Adrenal insufficiency (addison’s disease) Treatment with ACEI Angiotensin II receptor blocker Excessively rapid administration Movement of potassium from the intracellular to extracellular compartment –Tissue injury such as burns and crushing injuries –Extreme exercise or seizures –Acidosis

19. Manifestations of hyperkalemia Gastrointestinal manifestations –Anorexia, nausea, vomitting, intestinal cramps, diarrhea Cardiovascular manifestations –Ventricular fibrillation and cardiac arrest Neuromuscular manifestations –Paresthesias –Weakness –Muscle cramps

20. ECG changes in hyperkalemia Appearance a peaked T wave Widening of the QRS complex Prolongation of the PR interval Disappearance of the P wave

21. Treatment of hyperkalemia Decreasing intake or absorption of potasssium. Using calcium to antagonize the potassium. Using insulin and glucose Increasing potassium excretion –hemodialysis –peritoneal dialysis

22. Case1 A 40-year-old man with advanced acquired immunodeficiency syndrome (AIDS) presents with an acute chest infection. Investigation confirm a diagnosis of P.carinii pneumonia. Although he is treated appropriately, his serum sodium level is 118mmol/L. Tests of adrenal function are normal. What type of disorders happened to this man? What is the likely cause of this electrolyte disturbance?

23. Case 2 A 70-year-old woman who is taking furosemide (a loop diuretic) for congestive heart failure complains of weakness, fatigue, and cramping of the muscles in her legs. Her serum potassium is 2.0mmol/L, and her serum sodium is 140mmol/L. She also complains that she notices a “strange heart beat” at times. What is the likely cause of this woman’s symptoms? What would be the treatment for this woman?

24. Case 3 A 76-year-old woman was brought to the hospital because she was lethargic and refused to drink fluid. Her blood pressure is 100/60 mmHg. Serum sodium level is 170mmol/L, potassium level is 4.3mmol/L. What kind of electrolyte disturbance happened to this woman? What is the cause of this kind of disorder? What is the most severe outcome of this disorder?