Presentation on theme: "Chapter4(2) Potassium Disorders 1.Normal potassium metabolism: (1) Balance of potassium intake and excretion: K + intake : 50-200mmol/day from vegetable."— Presentation transcript:
Chapter4(2) Potassium Disorders 1.Normal potassium metabolism: (1) Balance of potassium intake and excretion: K + intake : 50-200mmol/day from vegetable and fruit K + excretion: kidney:approximately 90% of dietary potassium GI tract: only about 10 %
Major organ of excretion potassium: kidney Regulative site: renal distal tubule Hormone of major regulated: ADS Only the potassium output remains equivalent to intake every 24 hours, then to ensure Total body potassium 50-55mmol/kg B.W
Distal and collecting tubule secretion (Principal cells) (Principal cells) Regulated by: Regulated by: 1 Na + -K + ATPase 2 Electrochemical gradient of across the apical membrane 3 permeability of the apical membrane
Factors of affecting renal handling potassium Aldosterone Activates Na + -K + ATPase Sodium channels in the luminal membrane Na + reabsorption Aldosterone Activates Na + -K + ATPase Sodium channels in the luminal membrane Na + reabsorption Potassium channels in the luminal membrane Potassium channels in the luminal membrane Intracellular potassium content Secretion Intracellular potassium content Secretion Urine flow rate Secretion Urine flow rate Secretion Distal delivery of sodium Secretion Acid-base balance Secretion Acid-base balance: Acute acidosis Secretion
(2) Balance of potassium distribution: It is depended Na + —K + —ATPase on the cellular membrane(pump leak). consumption of1 ATP→pumping 3 Na + out off and 2 K + into the cell consumption of 1 ATP→pumping 3 Na + out off and 2 K + into the cell Total body potassium approximately 98% in ICF 50-55mmol/kg B.W approximately 2% in ECF ICF (3500mmol ): 150-160mmol/L ECF (70 mmol ): serum potassium 3.5-5.5mmol/L
Na + -K + ATPase ↓ [K + ]e : Na + -K + ATPase ↑ Influence factor of potassium distribution between ICF and ECF ( 1)Function of the Na + -K + pump: anoxia → Na + -K + ATPase ↓ [K + ]e : Na + -K + ATPase ↑ (2)Influence of acid-base balance: H + -K + exchanges across the cellular menbrane Acidosis company with hyperkalemia Alkalosis company with hypokalemia + Catecholamines : -R net influx into the cells (3) Influence of hormone: Insulin----K + into cell Aldosterone----increases excretion of K + Catecholamines : -R net influx into the cells -R plasma K + -R plasma K + (4) Rate of cell breakdown: crush syndrome (5) Plasma osmolality :
Function of the Potassium lThe Intracellular and extracellular potassium gradient is of major importance in maintenance resting cell membrane potential(Em) lThe abundant pool of intracellular potassium is necessary for maintenance of osmolality and hence the volume of body cells. lEssential for enzymatic reactions that regulate protein synthesis,growth,and metabolic processes
The relationship between serum potassium and total body potassium The clinical signs and symptoms are major depended on concentration of serum potassium.
Disorders of potassium homeostasis Disorders of potassium homeostasis Hypokalemia : Serum potassium 3.5 mmol/L ( Potassium depletion: ICF or total potassium ) l Hyperkalemia: Serum potassium 5.5 mmol/L
(2) Causes: a. Inadequate intake: Inability to eat; Fast and anorexia; Administration of K + -free parenteral solutions b. Excessive losses: Gastrointestinal losses – Vomiting; Diarrhea; suction; Fistula. Renal losses – Polyurine phase of acute renal failure,Diuretic therapy (except triamterene and spironolactone). Increased mineralocorticoid levels – primary and second aldosteronism Cushing’s syndrome Treatment with glucocorticoid hormones c. Intracellular shift: Alkalosis Insulin treatment Familial hypokalemic periodic paralysis Barium poisoning
(3) Effect on body: a. Effect on neuromuscular irritability Acute Hypokalemia: [K + ] I /[K + ] e → | Em |↑ (more negative) → ( E m -E r )↑→ Irritability↓→ Hyperpolarized block Nerve system manifestation: Depression, apathy, coma. Muscle system manifestation: striated muscle----Fatigue,weakness, flaccid paralysis smooth muscle----vessel dilation; decreased intestinal motion, abnormal distension,constipation and paralytic ileus. Chronic hypokalemia: The intracellular K + moves into ECF to maintain nearly normal RMP. So it has no above mentioned manifestation.
b. Effect on heart serum [K + ]↓→ reducing potassium conductance↓→ |E m |↓→ (E m -E r )↓→ irritability↑ serum [K + ]↓→ reducing potassium conductance↓→ decrease K + outward and accelerating Na + inward in 4 phase → automaticity ↑ serum [K + ]↓→ |E m |↓→ inward of Na + in phase 0 ↓ → conductivity↓ early stage or mild serum [K + ]↓→ accelerating of Ca 2+ inward in phase2 → contractivity↑ severe serum [K + ]↓→ Ca 2+ transport disorder ; ATP decreased; myocardium degeneration → contractivity↓ ECG: low T wave ; high U wave ; prolonged Q-T interval ; fallen S-T segment
c. Effects on kidney Hypokalemia → damage of renal tubules → inability to concentrate urine refractoriness to ADH polyuria, nocturia, low specific gravity urine,thirst prolonged severe hypokalemia: oliguria
d. Effects on acid-base balance Hypokalemia: more K + move out of cells metabolic alkalasis more H + and Na + of ECF move into cells H + of ECF↓→ with more H + are secreted from kidney abnormal acidic urine
(4) Principle of treatment a. In mild hypokalemia: replenishment of KCl by the oral route is preferable because it is safer than I.V. administration. b. In severe hypokalemia: adding KCl to glucose water intravenously at a final concentration of 40 mmol/L, and infusing KCl at a rate of 10-20 mmol/h, since KCl is an irritating substance. Usually the repair of hypokalemia needs several days. Never give KCl solution by direct intravenous injection to patients.
Hyperkalemia (1)Concept : Hyperkalemia is defined as a serum K + level greater than 5.5 mmol per liter. ( serum potassium >5.5mmol/L )
(2) Causes: A. Diminished renal excretion a. reduced GFR: oliguria phase of acute renal failure terminal phase of chronic renal failure b. reduced tubular secretion of K + addison’s disease; hypoaldosteronism application of potassium sparing diuretic(spironolactone, triamterene). B. Increased input of potassium excessive or rapid parenteral infusion of KCl solution C. Extracellular shifts a. acidosis b. cell destruction(trauma, burns, hemolysis, tumor lysis, rhabdomyolysis c. Familial hyperkalemic periodic paralysis
(3) Effects on body : A. Effects on neuromuscular irritability a. mild serum [K + ] ↑→ [K + ] I /[K + ] e ↓→ |E m |↓( as partial depolarization)→ (E m - E r )↓→ irritability↑→ Excitation （ Diarrhea,intestinal colic,paresthesia) b. severe serum [K + ]↑→ [K + ] I /[K + ] e ↓↓→ |E m |↓↓→|E m |≤ |E t | → Na + channel inactive → irritability↓→ Depolarized block （ weakness, paralysis, mental confusion and coma 。）
b. Effect on heart a. Mild serum [K + ] ↑→ [K + ] I /[K + ] e ↓→ |E m |↓( as partial depolarization)→ (E m - E r )↓→ irritability↑ b. Severe serum [K + ]↑→ [K + ] I /[K + ] e ↓↓→ |E m |↓↓→|E m |≤ |E t | → Na + channel inactive → irritability↓ Serum [K + ] ↑ →increased potassium conductance → accelerating K + outward and decreased Na + inward in 4 phase → autodepolarization ↓ → automaticity ↓ Serum [K + ] ↑ → [K + ] I /[K + ] e ↓→ |E m |↓ → inward of Na + in 0 phase ↓ → decreased velocity and extent of depolarization → conductivity↓ Serum [K + ] ↑ → depression Ca 2+ inward in 2 phase → contractivity↓ clinic signs and symptom :sinus bradycardia, heart block, asystole and heart arrest.
ECG : tall peaked and tent-shaped T wave; disappearance of P wave ; prolonged P-R interval; widening of QRS complex
c. effect on acid-base balance serum K + ↑→ K + of ECF move into cells and H + of ICF move out of cell; decreased secretion of H + due to intensive exchange between Na + and K + by distal tubules → metabolic acidosis with abnormal alkali urine
(4) Principles of treatment a. Treating primary disease b. Restriction of potassium intake c. Shift of K + from ECF into cell (insulin+glucose) d. Increased in K + excretion from body (furosemide, ethacrynic acid) e. Antagonizing the effects of hyperkalemia on heart (Ca 2+ or NaHCO 3 ）