§3. 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 Character of renal eliminating K + : The more ingestion, the more excretion; The less intake, the less exclusion; Not ingested, excretion goes on Regulative site: renal distal tubule Hormone of major regulated: Aldosterone(ADS)

Serum [K+]   ADS  Renal tubules conserve [Na+] and exclude [K+]  Serum [K+]   Restore normal

Only the potassium output remains equivalent to intake every 24 hours, then to ensure

Total body potassium 50-55mmol/kg B.W

Factors of affecting renal controlling potassium Aldosterone

Activates Na+-K+ ATPase   Sodium channels in the luminal membrane Na+reabsorption ;  Potassium channels in the luminal membrane

Intracellular potassium content  Urine flow rate 

 Secretion

Distal delivery of sodium 



 Secretion



 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 of 1 ATP→pumping 3 Na+ out off the cell 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

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 (3) Influence of hormone: Insulin----K+ into cell Aldosterone----increases excretion of K+ Catecholamines : -R net influx into the cells -R plasma K+  (4) Rate of cell breakdown: crush syndrome (5) Plasma osmolality:

Function of the Potassium The Intracellular and extracellular potassium gradient is of major importance in maintenance resting cell membrane potential ( Em ) The abundant pool of intracellular potassium is necessary for maintenance of osmolality and hence the volume of body cells. Essential 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 Serum potassium 3.5 mmol/L ( Potassium depletion: ICF or total potassium  )

Hypokalemia:

Hyperkalemia:

Serum potassium 5.5 mmol/L

Hypokalemia (1) Concept: Serum potassium5.5mmol/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, crush syndrome →rhabdomyolysis) c. Familial hyperkalemic periodic paralysis

(3) Effects on body : A. Effects on neuromuscular irritability a. mild serum [K+] ↑→ [K+]I/[K+]e↓→ |Em|↓( as partial depolarization)→ (Em- Et)↓→ irritability↑→ Excitation（ Diarrhea, intestinal colic, paresthesia) b. severe serum [K+]↑→ [K+]I/[K+]e↓↓→ |Em|↓↓→|Em|≤ |Et| → Na+channel inactive → irritability↓→ Depolarized block（weakness, paralysis, mental confusion and coma.）

b. Effect on heart a. Mild serum [K+] ↑→ [K+]i/[K+]e↓→ |Em|↓( as partial depolarization)→ (Em- Et)↓→ irritability↑ b. Severe serum [K+]↑→ [K+]i/[K+]e↓↓→ |Em|↓↓→|Em|≤ |Et| → 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↓→ |Em|↓ → inward of Na+ in 0 phase ↓ → decreased velocity and extent of depolarization → conductivity↓ Serum [K+] ↑ → depression Ca2+ 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

K+ ↑ H+

Somatic cell →Metabolic acidosis

↑K+ ↓H+

Na+↑ Na+↓

Renal cell→Paradoxical alkaline 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 (dialysis ,diuretics-spironolactone/ triamterene) e. Antagonizing the effects of hyperkalemia on heart (Ca2+ or NaHCO3）

Causes Hypokalemia inadequate intake excessive K+ losses intracellular shift

Hyperkalemia excess intake or gain decreased K+ losses extracellular shift

Effects on neuromuscular irritability Hypokalemia Irritability ↑

Hyperkalema Irritability↑→↓

Hyperpolarization

Depolarization

Hyperpolarized blocking

Partial depolarization ↓ Depolarization blocking

Manifestations of neuromuscle Hypokalemia Fatigue,weakness Muscle flabbiness paralysis Abdominal distention Paralytic ileus Shallow breathing

Hyperkalemia Paresthesia Muscle cramps Weakness, dizziness Diarrhea Intestinal colic Flabbiness paralysis

Effects on heart Hypokalemia irritability ↑ automaticity↑ conductivity ↓ contractivity↑→↓

hyperkalemia irritability↑→↓ automaticity↓ conductivity↓ contractivity↓

Effects on cardiovascular Hypokalemia

Hyperkalemia

postural hypotension cardiac arrhythmias Arrhythmias Cardiac arrest

Effects on ECG Hypokalemia

Hyperkalemia

Depressed S-T segment Flattening T wave Prolonged QRS complex High U wave

Peaked T wave Prolonged P-R interval Widening of QRS complex

Effects on acid-base balance and the kidney Hypokalemia metabolic alkalosis paradoxical aciduria polyuria, nocturia, thirst

Hyperkalemia

metabolic acidosis abnormal alkaline urine

Metabolic Effects Hypokalemia

 Release of Insulin/Glucose Intolerance.  Secretion of Grownth hormone, Renin, Aldosterone.

Hyperkalemia

 Release of Insulin/Glucagon

 Secretion of Aldosterone Prostaglandin

Treatment Hypokalemia potassium salt supplement ( oral is safer than I.V )

K+-sparing diuretics

Hyperkalemia change threshold potential ( intravenous Ca2+ ) shift K+ into cells ( Insulin and G.W i.v ) promote K+ loss from body diuretics polystyrene sodium resin use dialysis

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).

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?