Potassium Balance and Potassium Imbalance

1. Potassium Balance and Potassium Imbalance

2. Part Ⅰ

3. Potassium Balance Ⅰ Content and Distribution of Potassium in the Body Ⅱ Intake and Excretion of Potassium

4. Dietary K intake Serum [K+] round 4.5mmol/L 70~100mmol/day ECF 2% ICF Total body K content • More ingested, more excreted • Less ingested, less excreted • Not ingested, excretion goes on K+ [K+] 160mmol/L Excretion 31~57mmol/Kg body weight 98% of the total body potassium Skin trivial normally Colon 10% Kidneys > 80% Content, distribution, intake and excretion of K

5. Ⅲ Maintenance of Potassium Homeostasis —Distribution of K+ across the cell membrane and Regulation of renal K+ excretion

6. Distribution of Potassium across the Cell Membrane The Na+/K+ATPase membrane pump and permeability of ion channels

7. K+ Na+/K+-ATPase Na+ Catecholamine Insulin K+ H+ Influencing Factors 1.Hormones — insulin, glucagon, catecholamines, thyroid hormone 2.Serum [K+] 3.pH of ECF and plasma osmolality 4.Others — rate of cell breakdown, hypoxia, hypothermia, exercise [K+]↑

8. Cl- Na+/K+ATPase H+-K+ ATPase Na+/K+ATPase(Mg2+ activated) The nephron and collecting tubule Regulation of Renal Potassium Excretion • Filtration, reabsorption and secretion of potassium

9. Regulation of Renal Potassium Excretion • Filtration, reabsorption and secretion of potassium • Secretion of potassium in the distal and collecting tubules principal cells, with Na+/K+ATPase membrane pump, for secretion of K+

10. Na+ Na+ Cl- K+ Cl- K+ K+ CO2 H+ HCO3- Cl- Cl- K+ lumen blood Principal Cell CO2 Intercalated Cell

11. Regulation of Renal Potassium Excretion • Filtration, reabsorption and secretion of potassium • Secretion of potassium in the distal and collecting tubules • Reabsorption of K in the distal and collecting tubules, intercalated cells, with H+/K+-ATPase (proton pump) for reabsorption of K+

12. Regulation of Renal Potassium Excretion • Filtration, reabsorption and secretion of potassium • Secretion of potassium in the distal and collecting tubules • Reabsorption of K in the distal and collecting tubules intercalated cells, with H+/K+-ATPase (proton pump) for reabsorption of K+ • Factors influencing excretion of K+ by the distal and collecting tubules

13. Factors Influencing Excretion of K+ by the Distal and Collecting Tubules • Aldosterone — activates Na+/K+ATPase, increase membrane permeability to K • [K+] in the ECF • Flow rate of tubular fluid in the distal tubule • pH of ECF —↓pH inhibits Na+/K+ATPase

14. Ald + + + + + + + + flow rate - Factors Influencing Excretion of K+ by the Distal and Collecting Tubules lumen blood Na+ Na+ Cl- K+ Cl- [K+ ]↑ K+ K+ ① Principal Cell ② ③ CO2 CO2 [H+ ]↑ HCO3- H+ Cl- Cl- K+ Intercalated Cell

15. Maintenance of Potassium Homeostasis • Distribution of potassium across the cell membrane • Regulation of renal potassium excretion • Excretion of K by the Colon also controlled by aldosterone

16. Function of Potassium in the Body Ⅳ Function of Potassium in the Body • The part K+ plays in metabolism • Maintenance of the resting membrane potential of excitable cells • Maintenance and regulation of osmotic pressure and acid-base balance both in ICF and ECF

17. Part Ⅱ

18. Potassium Imbalance ---abnormal changes in [K+] in ECF

19. Hypokalemia Serum [K+]<3.5mmol/L,may or may not be associated with K deficit

20. Etiology and Pathogenesis Dietary intake Serum [K+] < 3.5mmol/L Total body K content ECF 2% ICF Excessive losses [K+] may or may not be decreased shifting —decreased (K deficit) or —normal G.I losses---diarrhea, vomiting Renal losses---diuretics, some diseases of the kidney Losses from the skin---profuse sweating, burns Crude cotton seed oil poisoning

21. Etiology and Pathogenesis Ⅰ. Inadequate Intake Fasting, anorexia, inability to eat, prolonged IV alimentation without K supplementation, alcoholism Ⅱ. Excessive Losses 1.Gastrointestinal losses Diarrhea →extrusion of large amount of alkaline liquid stool with a high content of K→K depletion, acidosis, ECF volume contraction →↑secretion of aldosterone Vomiting →mainly increased renal excretion of K+ due to metabolic alkalosis caused by loss of gastric acid, contraction of ECF volume

22. Etiology and Pathogenesis Ⅰ. Inadequate Intake Ⅱ. Excessive Losses 1.Gastrointestinal losses 2.Excessive renal losses (1)Diuretics→increased flow rate and delivery of Na+,Cl- and water to the distal tubule → increased Na+-K+ exchange; volume contraction →increased aldosterone → renal K excretion↑

23. Cl- Na+/K+ATPase H+-K+ ATPase Na+/K+ATPase(Mg2+ activated) The nephron and collecting tubule Regulation of Renal Potassium Excretion

24. Etiology and Pathogenesis Ⅰ. Inadequate Intake Ⅱ. Excessive Losses 1.Gastrointestinal losses 2.Excessive renal losses (1) Diuretics (2) Some diseases of the kidney Renal tubular acidosis

25. Excessive Renal Losses (1) Diuretics (2) Some diseases of the kidney Renal tubular acidosis Diuretic recovery phase of acute renal failure (3) Antibiotics (4) Excess of adrenocortical hormones Aldosteronism, Cushing’s syndrome (5) Magnesium deficiency Diuretic recovery phase of acute renal failure

26. Cl- Na+/K+ATPase H+-K+ ATPase Na+/K+ATPase(Mg2+ activated) The nephron and collecting tubule Regulation of Renal Potassium Excretion

27. Case Report A female patient, 42 years old, was admitted to the affiliated hospital of the Sichuan Med.College as an emergency case on April 4 1978, with a chief complaint of decreased food intake, nausea and frequent vomiting for 20 days. She had a history of diabetes mellitus for 3 years. Diagnosis: Diabetic ketoacidosis, which is a medical emergency. She was treated with insulin, with success. She was also found to have infection of the urinary tract as well as severe hypokalemia (the serum [K+] was around 2mmol/L). Therefore she was given large doses of gentamycin for 33 days. KCl was also administered, both by mouth and IV instillation, in large doses, for 41 days. However, hypokalemia persisted (2.55mmol/L).

28. To the surprise of the doctor, the patient suddenly developed spastic rigidity of the limbs. It was until then, 41days after admission, the doctor examined the serum [Mg2+], it was very low:0.2mmol/L!(The normal range of serum [Mg2+] being 1.5~2.5mmol/L). IV MgSO4 was immediately given, and also for several days, with complete success! The doses of KCl was reduced, however, the serum [K+] rose to normal levels within 3 days! Serum [Mg2+] also turned normal. No adverse reactions.(《中华内科杂志》1980年1月) Questions:1. What is the cause or what are the causes of hypokalemia and hypomagnesemia in this patient? 2. Why did the doctor fail to diagnose hypomagnesemia earlier?

29. Excessive Renal Losses (1) Diuretics (2) Some diseases of the kidney Renal tubular acidosis Diuretic recovery phase of acute renal failure (3) Antibiotics (4) Excess of adrenocortical hormones Aldosteronism, Cushing’s syndrome (5) Magnesium deficiency (6) Alkalosis

30. Etiology and Pathogenesis Ⅰ.Inadequate Intake Ⅱ.Excessive Losses 1. Gastrointestinal losses 2. Excessive renal losses 3. Excessive losses from the skin Profuse sweatings, burns or scalds

31. K+ Na+/K+-ATPase Na+ Albuterol Insulin K+ H+ Etiology and Pathogenesis Ⅰ.Inadequate Intake Ⅱ.Excessive Losses Ⅲ.Shifting of K+ from the ECF to ICF 1.Overdose of insulin 2.-adrenergic agonist overdose

32. K+ Na+/K+-ATPase Na+ Albuterol Insulin K+ H+ Etiology and Pathogenesis Ⅰ.Inadequate Intake Ⅱ.Excessive Losses Ⅲ.Shifting of K+ from the ECF to ICF 1.Overdose of insulin 2.-adrenergic agonist overdose 3.Alkalosis 4.Barium poisoning 5.Familial hypokalemic periodic paralysis

33. Etiology and Pathogenesis Ⅰ.Inadequate Intake Ⅱ.Excessive Losses Ⅲ.Shifting of K+ from the ECF to ICF Crude Cotton Seed Oil poisoning

34. Effects on the Body — factors influencing the effects: the underlying diseases, the degree of hypokalemia and rapidity of its development, the ratio of [K+]i / [K+] e

35. +35 0 Millivolts -60 Threshold -90 Milliseconds Effects on Neuromuscular Excitability Nernst equation Em= -60lg[K+]icf / [K+]ecf (mv) The Resting Membrane Potential (RMP) and Action Potential (AP) of a skeletal muscle cell in the normal state

36. RMP more negative than normal [K+]i / [K+]e ↑ Acute Hypokalemia hyperdepolarization block, excitability↓ muscle weakness, flaccid paralysis, smooth muscle symptoms

37. 30 Action potential (AP) 0 -30 -60 TMP RMP -90 -120 Normal Low [K+] High [K+] mv The effects of serum K+ concentration on cellular membrane excitability

38. Chronic Hypokalemia ratio of [K+]ito[K+]e may be normal, RMP and excitability unchanged, interfering with cellular metabolism and vasodilation of muscles during exercise

39. Effects on the Heart A Brief Review of the Bioelectric Phenomena of the Heart

40. a: effective refractory period; b: relative refractory period c: supranormal period RMP and AP of a Ventricular Muscle Cell of the Heart

41. The Membrane Potential of Atrial Muscle, and Purkinje’s Fiber Atrial muscle Purkinje’s fiber 40 1 1 +20 2 2 0 -20 3 3 0 0 40 60 4 4 80 4 4 100 RMP max.diast.potential

42. 1.Effects on excitability RMP<-90mv, excitability Ca2+ inflow plateau, ERP shortened Phase 3, SNP prolonged AP prolonged

43. normal low [K+]e a.mus. v.mus. Threshold potential repolarization normal prolonged Effects of low serum [K+] on the action potential of the myocardial cell

44. 2. Effects on autorhythmicity K channel conductance of the cell membrane of the fast response autonomic cells acceleration of spontaneous diastolic depolarization, autorhythmicity

45. The Membrane Potential of Purkinje’s Fiber 1 2 normal 0 3 hypokalemia 4 4 max.diast.potential

46. 3. Effects on conductivity Amplitude and rapidity of phase 0 depolarization smaller than normal conductivity

47. Cardiac arrhythmias due to increased excitability, shortened ERP, prolonged SNP, increased autorhythmicity and decreased conductivity

48. The conducting system of the heart

49. a: effective refractory period; b: relative refractory period c: supranormal period RMP and AP of a Ventricular Muscle Cell of the Heart

50. conductivity and cardiac arrhythmias —— reentry of excitation