Potassium Imbalance

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Potassium Imbalance

  1. 1. Disorders of potassium metabolism Yu-Hong Jia, Ph.D Department of pathophysiology Dalian medical university
  2. 2. Potassium function <ul><li>Participates in many metabolic processes, e.g. regulation of protein and glycogen synthesis. </li></ul><ul><li>Maintain osmotic and acid-base balance between intra- and extra- cell. </li></ul><ul><li>Maintain resting membrane potential (RMP) of cellular membrane. </li></ul>
  3. 3. Ⅰ . Normal potassium metabolism
  4. 4. K + Na + ATPase K + H + K + channel 140-160 mmol/L 4.2±0.3mmol/L 50-200mmol/day K + ingestion Kidney colon skin (90%) insulin β-adrenergic agonist ECF [K + ] K + : 50-55mmol/kg B.W toxin (Ba) acid-base state Pump-leak
  5. 5. ① free filtration ② reabsorption (90% of filtered potassium) ③ secretion or reabsorption (in normal diet, secretion is major) K + K + K + Proximal tubule &Henle’s loop Distal tubule & Collecting duct
  6. 6. Three elements for achieving potassium secretion: 1. Na + -K + -ATPase on basolateral membrane 2. Permeability of luminal membrane to K+ 3. Electrochemical gradient from blood to tubular lumen ATPase Na + K + K + channel K + Principal cell Basolateral membrane luminal membrane peritubular interstitial tubular lumen K +
  7. 7. factors affecting renal secretion of K + <ul><li>↑ the activity of Na + -K + -ATPase in principle cells; </li></ul><ul><li>↑ luminal membrane permeability to K + </li></ul><ul><li>↑ the activity of Na + -K + -ATPase </li></ul><ul><li>↑ luminal membrane permeability to potassium </li></ul><ul><li>↓ K + concentration gradient between interstitial fluid and tubular cell ->↓K + counterflow into the interstitial fluid </li></ul><ul><li>↑ urinary flow rate-> rapidly remove the K + secrected by tubular cells->↓ the K + concentration in tubular lunmen->↑K + concentration gradient across luminal membrane->↑ K + secretion </li></ul><ul><li>Increased H + concentration inhibits Na + -K + -ATPase in principle cells ->↓ K + secretion, on the contrary, ↓H + concentration->↑K + secretion </li></ul><ul><li>aldosterone ( ADS ) </li></ul><ul><li>Extracellular K + concentration </li></ul><ul><li>Urinary flow rate </li></ul><ul><li>Acid-base state </li></ul>↑ ↑ ↑ K + secretion ↑ K + secretion ↑ K + secretion
  8. 8. K + Na + ATPase K + H + K + channel 140-160 mmol/L 4.2±0.3mmol/L 50-200mmol K + ingestion Kidney colon skin (90%) insulin β-adrenergic agonist ECF [K + ] 50-55mmol/kg B.W ADS ECF K + concentration Urinary flow rate acid-base state toxin drug acid-base state
  9. 9. Ⅱ . Disorders of potassium metabolism
  10. 10. Classification of Disorders of potassium metabolism: <ul><li>Hypokalemia </li></ul><ul><ul><li>Serum potassium concentration <3.5mmol/L </li></ul></ul><ul><li>Etiology and pathogenesis </li></ul><ul><li>(1). ↓ Potassium intake </li></ul><ul><li>(2). Potassium shift from extracellular to intracellular fluid </li></ul><ul><li>(3). ↑potassium excretion </li></ul><ul><li>Hyperkalemia </li></ul><ul><ul><li>Serum potassium concentration >5.5mmol/L </li></ul></ul><ul><li>1. Etiology and pathogenesei </li></ul><ul><li>(1). ↑ Potassium intake </li></ul><ul><li>(2). Potassium shift from intracellular to extracellular fluid </li></ul><ul><li>(3). ↓ potassium excretion </li></ul>hypokalemia, hyperkalemia Potassium deficit Hypokalemia, normal serum potassium
  11. 11. Hypokalemia: etiology and pathogenesis (3). ↑K + excretion <ul><li>Unable to eat, i.e. coma, digestive tract obstruction </li></ul><ul><li>Fasting, i.e. after operation of digestive tract </li></ul>(1). ↓K + intake (2). ↑K+ shift from ECF to ICF <ul><li>Use of some drug, i.e. insulin, β -adrenergic agonist </li></ul><ul><li>Toxin poisoning, i.e. barium </li></ul><ul><li>Alkalosis </li></ul><ul><li>Familial hypokalemic periodic paralysis </li></ul><ul><li>Via kidney </li></ul><ul><li>Via gastrointestinal tract </li></ul><ul><li>Via skin </li></ul>
  12. 12. Familial hypokalemic periodic paralysis <ul><li>A rare inherited disorder with autosomal dominant trait. </li></ul><ul><li>Characteristic feature: recurrent episodes of muscle weakness accompanied with hypokalemia, automatically relieved without treatment. </li></ul><ul><li>Mechanism: related with mutation of genes coding for skeletal muscle L-type calcium channel, sodium channel α subuint, or potassium channel accessory subunit. </li></ul>
  13. 13. Excessive renal loss of potassium <ul><li>Use of certain diuretic agents i.e. acetazolamide and furosemide. </li></ul><ul><li>Primary and secondary aldosteronism </li></ul><ul><li>Alkalosis </li></ul><ul><li>Renal tubular acidosis </li></ul><ul><li>Magnesium deficit </li></ul>K + H + alkalosis ↑ Urinary flow rate ↓ ECF volume-> secondary ADS increase
  14. 14. Renal tubular acidosis (RTA) <ul><li>Acidosis caused by renal tubular dysfunction. </li></ul><ul><ul><li>Type ⅠRTA: distal renal tubular acidosis, caused by reduced H + secretion in the distal nephron </li></ul></ul><ul><ul><li>Type ⅡRTA: proximal renal tubular acidosis, caused by impaired reabsorption of HCO 3 - in the proximal tubule. </li></ul></ul>
  15. 15. Hypokalemia: etiology and pathogenesis (3). ↑K + excretion <ul><li>Unable to eat, i.e. coma, digestive tract obstruction </li></ul><ul><li>Fasting, i.e. after operation of digestive tract </li></ul>(1). ↓K + intake (2). ↑K+ shift from ECF to ICF <ul><li>Use of some drug, i.e. insulin, β -adrenergic agonist </li></ul><ul><li>Toxin poisoning, i.e. barium </li></ul><ul><li>Alkalosis </li></ul><ul><li>Familial hypokalemic periodic paralysis </li></ul><ul><li>Via kidney </li></ul><ul><li>Via gastrointestinal tract </li></ul><ul><li>Via skin </li></ul>Use of certain diuretic agents, Primary and secondary aldosteronism Alkalosis, Renal tubular acidosis, Magnesium deficit
  16. 16. Excessive gastrointestinal loss of K + — vomit, diarrhea, gastric suction <ul><li>Direct K + loss through gastrointestinal juice </li></ul><ul><li>Gastrointestinal juice loss-> extracellular fluid volume decrease-> ADS secretion increase-> renal excretion of K + increase </li></ul><ul><li>vomiting-> gastric acid (HCl) loss -> alkalosis is resulted in ->K + shift into cells via H + -K + exchange and increased renal excretion of K + </li></ul>
  17. 17. Hypokalemia: etiology and pathogenesis (3). ↑K + excretion <ul><li>Unable to eat, i.e. coma, digestive tract obstruction </li></ul><ul><li>Fasting, i.e. after operation of digestive tract </li></ul>(1). ↓K + intake (2). ↑K+ shift from ECF to ICF <ul><li>Use of some drug, i.e. insulin, β -adrenergic agonist </li></ul><ul><li>Toxin poisoning, i.e. barium </li></ul><ul><li>Alkalosis </li></ul><ul><li>Familial hypokalemic periodic paralysis </li></ul><ul><li>Via kidney </li></ul><ul><li>Via gastrointestinal tract </li></ul><ul><li>Via skin </li></ul>Use of certain diuretic agents, Primary and secondary aldosteronism Alkalosis, Renal tubular acidosis, Magnesium deficit Vomit, dirrhea, gastric suction Heavy sweat in hot environment
  18. 18. Hyperkalemia: etiology and pathogenesis (3). ↓ K + excretion <ul><li>Rapid intravenous infusion of KCl or potassium salt of penicillin </li></ul>(1). ↑ K + intake (2). ↑K+ shift from ICF to ECF <ul><li>Deficiency of insulin, i.e. diabetes mellitus </li></ul><ul><li>β -adrenergic antagonist </li></ul><ul><li>acidosis </li></ul><ul><li>Cell injury, i.e. trauma, hemolysis </li></ul><ul><li>Familial hyperkalemic periodic paralysis </li></ul><ul><li>Glomerular filtration rate decrease, i.e. oliguric stage of renal failure </li></ul><ul><li>Renal tubular secretion of K + decrease </li></ul><ul><ul><li>↓ ADS, i.e. adrenal cortical insufficiency ( Addison disease) </li></ul></ul><ul><ul><li>acidosis </li></ul></ul>
  19. 19. Familial hyperkalemia periodic paralysis <ul><li>A rare inherited disorder with autosomal dominant trait. </li></ul><ul><li>A sudden increase in serum potassium concentration and muscle paralysis </li></ul>
  20. 20. 2. Alterations of metabolism and function <ul><ul><li>Dysfunction related with abnormal resting membrane potential </li></ul></ul><ul><ul><li>Damage related with cellular metabolism dysfunction </li></ul></ul><ul><ul><li>Effect on acid-base balance </li></ul></ul>
  21. 21. <ul><li>Permeability RMP negative value </li></ul><ul><ul><ul><li>↓ -> ↓ i.e. normal -90mv -> -70mv </li></ul></ul></ul><ul><li>Extracellular K + concentration [K + ] e RMP negative value </li></ul><ul><li>↓ -> ↑ </li></ul><ul><li>↑ -> ↓ </li></ul>Electrical gradient Chemical gradient K + 140-160mmmol/L 4.2±0.3mmol/L Resting membrane potential (RMP) Excitable cell <ul><li>Cell membrane permeability to K + </li></ul><ul><li>K + transmembrane concentration gradient </li></ul>- - - - - + + + + + Na + ATPase RMP ≈ ﹣ 59.5lg Intracellular K + concentration extracellular K + concentration
  22. 22. <ul><li>Action potential </li></ul>is a wave of depolarization and repolarization that moves across a cell membrane <ul><li>Threshold potential </li></ul>The critical value of depolarization that can provoke action potential.
  23. 24. hypokalemia <ul><li>(1). Effects on neuromuscular irritability: ↓ </li></ul><ul><ul><li>skeletal muscle: flabbiness, weakness and even paralysis </li></ul></ul><ul><ul><li>smooth muscle: abdominal distention, vomit, even paralytic ileus. </li></ul></ul><ul><li>(1). Effects on neuromuscular irritability: ↑->↓ </li></ul><ul><ul><li>skeletal muscle: prick, sting, abnormal sense-> weakness, paralysis </li></ul></ul>hyperkalemia
  24. 25. Irritability (excitability) <ul><li>the ability to produce action potential </li></ul><ul><li>determined by the difference between RMP and the threshold potental, and state of sodium channel </li></ul><ul><ul><li>Difference increase -> irritability ↓ </li></ul></ul><ul><ul><li>Difference diminish -> irritability↑ </li></ul></ul><ul><ul><li>Difference overly diminish->irritability↓ </li></ul></ul>↑ -> ↓ ↓ ↓ hyperkalemia ↓ ↑ ↑ hypokalemia irritability Difference (between RMP and threshold potential) RMP (negtive value) Neuromuscular cell
  25. 26. hypokalemia <ul><li>(2). Effects on the heart </li></ul><ul><li>alterations of myocardial electrophysiology </li></ul><ul><ul><li>Irritability: ↑ </li></ul></ul><ul><ul><li>Conductivity: ↓ </li></ul></ul><ul><ul><li>Contractility: ↑ </li></ul></ul><ul><ul><li>Automaticity : ↑ </li></ul></ul><ul><li>Alterations of electrocardiogram </li></ul><ul><ul><li>prolonged P-R interval, widen QRS wave </li></ul></ul><ul><ul><li>Depressed S-T segment </li></ul></ul><ul><ul><li>Flattened T wave </li></ul></ul><ul><li>Arrhythmia </li></ul><ul><ul><li>i.e. sinus tachycardia </li></ul></ul><ul><li>(2). Effects on the heart </li></ul><ul><li>alterations of myocardial electrophysiology </li></ul><ul><ul><li>Irritability: ↑->↓ </li></ul></ul><ul><ul><li>Conductivity: ↓ </li></ul></ul><ul><ul><li>Contractility: ↓ </li></ul></ul><ul><ul><li>Automaticity: ↓ </li></ul></ul><ul><li>Alterations of electrocardiogram </li></ul><ul><ul><li>prolonged P-R interval, widen QRS wave </li></ul></ul><ul><ul><li>Peaking of T wave </li></ul></ul><ul><li>Arrhythmia </li></ul><ul><ul><li>i.e. sinus bradycardia </li></ul></ul>hyperkalemia
  26. 27. <ul><li>Irritability (excitability) </li></ul><ul><li>determined by the difference between RMP and the threshold potental, and state of sodium channel </li></ul><ul><ul><li>Difference increase -> irritability ↓ </li></ul></ul><ul><ul><li>Difference diminish -> irritability↑ </li></ul></ul><ul><ul><li>Difference overly diminish->irritability↓ </li></ul></ul><ul><li>A special point about the effect of hypokalemia on the heart : </li></ul><ul><ul><li>Hypokalemia reduces the permeability of cardiac cell membrane to K + , but not the permeability of neuromuscular cells membrane to K + . </li></ul></ul>↑ -> ↓ ↓ ↓ hyperkalemia ↑ ↓ ↓ hypokalemia irritability Difference (between RMP and threshold potential) RMP (negtive value) heart
  27. 28. <ul><li>conductivity </li></ul><ul><li>Determined by the depolarization velocity and amplitude of phase 0 of action potential, and the depolarization velocity is determined by the difference between RMP and threshold potential. </li></ul><ul><ul><li>Difference increase -> conductivity ↑ </li></ul></ul><ul><ul><li>Difference diminish -> conductivity ↓ </li></ul></ul>↓ ↓ ↓ hyperkalemia ↓ ↓ ↓ hypokalemia conductivity Difference (between RMP and threshold potential) RMP (negtive value) heart
  28. 29. <ul><li>contractility </li></ul><ul><li>Determined by Ca 2+ inward flow which is inhibited by K + in the extracellular fluid. </li></ul>↓ ↓ hyperkalemia ↑ ↑ hypokalemia contractility Ca 2+ inward flow heart
  29. 30. <ul><li>automaticity </li></ul><ul><li>Attributed to the automatic depolarization of cardiac rhythmic cell at the phase 4 of action potential. </li></ul><ul><li>The automatic depolarization is caused by a net inward current which make membrane depolarization till threshold. </li></ul><ul><li>The net inward current is mainly composed of degressive outward potassium current and progressive inward sodium current. </li></ul>↓ ↓ ↑ hyperkalemia ↑ ↑ ↓ hypokalemia automaticity Net inward current Membrane Permeability to K + heart
  30. 31. <ul><li>P wave – atria depolarize </li></ul><ul><li>QRS wave – ventricles depolarize phase 0 </li></ul><ul><li>T wave — ventricles repolarize phase 3 </li></ul><ul><ul><li>Outward K + current </li></ul></ul><ul><li>S-T segment — ventricles repolarize phase 2 </li></ul><ul><ul><li>Inward Ca 2+ current </li></ul></ul><ul><ul><li>Outward K + current </li></ul></ul><ul><li>P–R interval — from start of atria depolarization to start of QRS complex </li></ul>Comparation between action potential and normal electrocardiogram <ul><li>A— atria action potential </li></ul><ul><li>V— ventricle action potential </li></ul>
  31. 32. <ul><li>Hypokalemia: </li></ul><ul><ul><li>↓ conductivity-> prolonged P-R interval, widen QRS wave </li></ul></ul><ul><ul><li>↓ Membrane permeability to K+ </li></ul></ul><ul><li>Hyperkalemia: </li></ul><ul><ul><li>↓ conductivity-> prolonged P-R interval, widen QRS wave </li></ul></ul><ul><ul><li>↑ Membrane permeability to K+ </li></ul></ul>ventricles repolarize phase 3 accelerate Peaking of T wave ventricles repolarize phase 3 prolong ventricles repolarize phase 2 inward calcium current accelerate Depressed S-T segment Flattened T wave
  32. 33. hypokalemia <ul><li>(3). Effects on acid-base balance </li></ul><ul><ul><li>alkalosis </li></ul></ul><ul><ul><li>Paradoxical aciduria </li></ul></ul><ul><li>(3). Effects on acid-base balance </li></ul><ul><ul><li>acidosis </li></ul></ul><ul><ul><li>Paradoxical alkaline urine </li></ul></ul>hyperkalemia ↓[K + ] ECF H + -K + exchange ↓[H + ] ECF ↑[H + ] ICF ↑Renal excretion of H + aciduria K + shift out of cells H + shift into cells alkalosis (Paradoxical aciduria) ↑[K + ] ECF H + -K + exchange ↑[H + ] ECF ↓[H + ] ICF ↓Renal excretion of H + Alkaline urine K + shift into cells H + shift out of cells acidosis (Paradoxical alkaline urine)
  33. 34. hypokalemia <ul><li>(4). Damage related with metabolism dysfunction </li></ul><ul><ul><li>polyuria </li></ul></ul><ul><ul><li>Renal tubulointerstitial damage </li></ul></ul>

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