A serum potassium concentration of less than 3.5 mmol/L (or mEq/L) is called hypokalemia. The decrease in serum potassium concentration is often accompanied by a decrease in total body potassium, in addition to those caused by abnormal distribution of potassium in the body.
(I) Causes and mechanisms of occurrence
The occurrence of hypokalemia includes three basic causes: insufficient potassium intake, excessive potassium loss and abnormal potassium distribution in the body (excessive entry of potassium into the cells).
1. Insufficient potassium intake
Meat, fruits and many vegetables are rich in potassium, so hypokalemia does not occur with a normal diet. In some disease cases, such as patients with esophageal cancer and gastric pyloric obstruction, the inability to eat or fasting, and the lack of attention to potassium supplementation during intravenous infusion can cause a decrease in blood potassium.
2.Loss of too much potassium
Potassium can be lost through the digestive tract, with urine or sweat. Among them, the most common and important clinical causes of potassium loss are through the digestive tract and kidney.
(1) Potassium loss through the gastrointestinal tract.
In cases of severe vomiting, diarrhea, intestinal fistula or gastrointestinal decompression, a large amount of digestive fluid is lost, which can cause potassium loss. At the same time, fluid loss can cause a decrease in blood volume and an increase in aldosterone secretion, so it may also increase renal potassium excretion (note: if the flow rate of the distal tubule is reduced, renal potassium excretion does not necessarily increase). In patients with vomiting or diarrhea, although there is a loss of potassium, the blood volume is reduced and the blood is concentrated, so the potassium may still be in the normal range for a while or the degree of hypokalemia is not yet serious.
When the blood is “diluted” after rehydration, the signs and symptoms of hypokalemia may be apparent, which is also known as “dilutional hypokalemia”.
(2) Transrenal potassium loss.
① Excessive renal potassium loss due to increased distal renal tubular flow.
1) High use of diuretics, such as mannitol, an osmotic diuretic, which increases the flow rate in the distal tubule; acetazolamide, a diuretic that inhibits the carbonic anhydrase activity of the proximal tubule, which decreases the production and excretion of H+ by the renal tubular epithelium and the reabsorption of Na+ by the proximal tubule, resulting in increased Na+ flow to the distal tubule and enhanced Na+-K+ exchange; and acetazolamide, a diuretic that inhibits the flow of Cl- and Na+ from the thick segment of the ascending branch of the medullary loop and the beginning of the distal tubule. The sodium-discharging diuretics tachykinuria, diuretic acid, or chlorothiazide diuretics, which inhibit the reabsorption of Cl- and Na+ at the beginning, increase both the distal flow rate and the Na+-K+ exchange in the distal renal unit.
2) Renal insufficiency: e.g., increased urea excretion during the polyuric phase of acute renal failure, causing osmotic diuresis and accelerated distal flow rate; interstitial renal disorders such as chronic nephritis or pyelonephritis, due to impaired sodium and water reabsorption by proximal tubules and medullary loops, resulting in accelerated distal flow rate and enhanced Na+ – K+ exchange.
(2) Increased aldosterone: Aldosterone is the main salt corticosteroid that promotes sodium reabsorption and potassium and hydrogen secretion, so primary or secondary aldosteronism, which can cause potassium loss. Increased secretion of other corticosteroids with similar effects, such as Cushing’s syndrome, congenital adrenal hyperplasia or patients with long-term heavy use of corticosteroids, can also lead to hypokalemia.
③ Potassium loss due to increased negative transmembrane potential in the renal tubules.
1) Heavy use of certain antimicrobial agents (gentamicin, carbenicillin, etc.) increases the negative ions that are not easily absorbed in the distal tubule and promotes potassium excretion.
2) In type II renal tubular acidosis, HCO3- reabsorption in the proximal tubule is impaired, and negative ions ( HCO3- ) in the distal tubule are increased, promoting the secretion and excretion of K+.
④ Potassium loss caused by hypomagnesemia: when the body is deficient in magnesium, the Na+-K+-ATP enzyme in the epithelial cells of the ascending branch of the medullary loop is inactivated, causing impaired potassium reabsorption and potassium loss. It is also believed that hypomagnesemia can promote potassium excretion by aldosterone secretion. If hypokalemia and hypocalcemia coexist, magnesium deficiency is often indicated.
(5) Other: In type I tubular acidosis, distal tubular H+ secretion is impaired, resulting in enhanced Na+ – K+ exchange and enhanced renal potassium excretion.
(3) Potassium loss through the skin: strong physical work in a hot environment causes a lot of sweating, which can cause low potassium if not supplemented with appropriate electrolytes.
3. Potassium transfer to the cells
(1) Alkalosis: In alkalosis, as a compensatory mechanism for the disturbance of acid-base balance, H+ is transferred from intracellular to extracellular, and K+ enters intracellular, so that the blood potassium decreases; at this time, the renal tubular Na+-H+ exchange is weakened and Na+-K+ is enhanced, so the renal potassium excretion also increases.
(2) Use of insulin: In diabetes mellitus, cellular utilization of glucose is impaired, glycogen synthesis is reduced and glycogen isogenesis is enhanced, intracellular macromolecules are broken down and potassium is transferred to extracellular fluid, and potassium loss is increased through diabetic diuresis, and the body is in a state of reduced total potassium, at this time insulin is used for treatment, which can make cells use glucose to synthesize glycogen and make extracellular potassium enter into cells; at the same time, insulin has the function of enhancing Na+-K+ exchange and the function of enhancing Na+-K+ exchange. At the same time, insulin can strengthen the activity of Na+-K+-ATP enzyme and promote the entry of potassium into the cell. If potassium is not taken care of, hypokalemia can be caused.
(3) Hypokalemic periodic paralysis: Potassium transfer into the cells is thought to be the mechanism of this disorder. Patients may experience transient limb paralysis, lower blood potassium and reduced urinary potassium during episodes. Factors that promote the entry of potassium into the cells (e.g., post-exercise, high-sugar diet, stressful conditions causing adrenaline release, etc.) can induce periodic paralysis.
(4) Barium poisoning: such as barium chloride, barium carbonate, barium hydroxide, etc. poisoning. When barium poisoning, Na+ -K+ -ATP enzyme activity is enhanced, and potassium continuously enters the cell, plus blocking the potassium channels on the cell membrane from intracellular to extracellular, so that the serum potassium is reduced.
(b) The effect of hypokalemia on the organism
The functional and metabolic changes caused by hypokalemia and their severity are related to the speed, magnitude and duration of the decrease in blood potassium. The faster the blood potassium decreases, the lower the blood potassium concentration and the greater the impact on the body. The more pronounced clinical manifestations are usually seen when serum potassium falls below 3.0 mmol/L or 2.5 mmol/L. In chronic potassium loss, the clinical symptoms are less pronounced, despite the lower potassium concentration. However, this effect varies considerably between individuals.
The clinical symptoms of hypokalemia are mainly neuromuscular and cardiac. The main neuromuscular symptoms are muscle weakness, muscle paralysis, abdominal distention and paralytic intestinal obstruction. Cardiac symptoms include arrhythmia, digitalis toxicity, and electrocardiogram abnormalities. In addition, hypokalemia can also cause disorders of acid-base balance, kidney damage and cellular metabolism disorders.
1. Effects on nerve and muscle
Hypokalemia has a significant effect on the excitability and conductivity of nerve and muscle tissue. In acute hypokalemia, the extracellular fluid potassium concentration ([K+]e) decreases and the intracellular fluid potassium concentration ([K+]i) remains unchanged, as a result, the [K+]i/[K+]e ratio increases, the intracellular potassium outflow increases, the absolute value of membrane resting potential ( Em ) increases, and the distance between it and the threshold potential ( Et ) increases ( Em – Et ), so that the stimulation threshold of excitation must also increase, thus causing the excitability of neuromuscular cells to decrease. The excitability of neuromuscular cells decreases, and in severe cases, excitability even disappears, which is also called hyperpolarization block.
At the same time, the slope of the 0-phase depolarization curve becomes larger and the frontal potential decreases because the Em-Et distance decreases and the potential change before the action potential is smaller than normal, so the neuromuscular conductance is also reduced.
The most prominent manifestation of hypokalemia is skeletal muscle relaxation and weakness, even causing flaccid paralysis. In general, when serum potassium is below 3.0 mmol/L, symptoms of limb weakness can be observed, often involving the lower extremities first, and later affecting the upper extremities and trunk muscles. Below 2.5 mmol/L, flaccid paralysis may occur, and in severe cases, death may result from respiratory muscle paralysis.
Smooth muscle weakness is manifested by decreased gastrointestinal motility, decreased or absent bowel sounds, abdominal distention (flatulence), and even paralytic intestinal obstruction.
Neurological involvement is manifested by muscle aches and pains or abnormal sensation, reduced muscle tone, and diminished or absent tendon reflexes. A few patients may develop central nervous system signs and symptoms such as mental depression, unresponsiveness, disorientation, drowsiness or even coma.
In chronic hypokalemia, the [K+]i/[K+]e ratio changes less because the extracellular fluid potassium concentration decreases slowly and extracellular potassium can be replenished by intracellular potassium escape, so the clinical symptoms of reduced muscle excitability are not obvious. Chronic hypokalemia causes a significant intracellular potassium deficiency, resulting in impaired cellular metabolism and swelling of muscle cells.
During exercise, the increased release of potassium from skeletal muscle involved in exercise increases the local vascular potassium concentration, which stimulates local vasodilation and increased blood flow as a normal physiological response. In patients with hypokalemia, the release of potassium from exercising skeletal muscle decreases, and local vasodilation and increased blood flow are inadequate, thus causing pathological changes such as muscle contracture and ischemic necrosis and rhabdomyolysis.
It is worth noting that, in addition to [K+]e, changes in extracellular fluid [Ca2+] and [H+] have a significant impact on neuromuscular excitability. An increase in extracellular fluid [Ca2+] inhibits the phase 0 Na+ inward flow, i.e., it affects the depolarization process, thus increasing Et (decreasing the negative value).
The result is similar to that of hypokalemia, as the Em – Et distance increases, causing a decrease in muscle excitability. The decrease in blood [Ca2+] depresses the Et value (negative value increases), and the smaller stimulus can depolarize the myocyte membrane to reach Et and generate action potential, so the muscle excitability increases, and clinically there are symptoms such as hand and foot twitching.
2. Effects on the heart
The main effect of hypokalemia on the heart is to cause arrhythmia, and in serious cases, ventricular fibrillation, leading to heart failure. This is related to the abnormal changes in myocardial electrophysiology caused by a significant decrease in blood potassium.
The effects of changes in blood potassium concentration on myocardial electrophysiology.
① Membrane potential: According to the Nernst equation, the membrane resting potential should be: Em = -59.5 log([K+]i/[K+]e), so abnormal blood potassium can cause Em to change.
② Permeability of the cardiomyocyte membrane to K+: The membrane permeability to potassium is greatest when the cardiomyocyte membrane is at normal resting potential.
If [K+]e decreases, although the concentration difference between intracellular and extracellular potassium ions increases, i.e., the concentration gradient increases, which facilitates the outflow of potassium and may cause the absolute value of Em and the distance between Em and Et to increase, but because the membrane permeability to potassium decreases more obviously, the outflow of potassium actually slows down in the repolarization phase 3 due to the decrease of potassium permeability. Therefore, the Em-Et interval decreases and myocardial excitability increases.
(iii) Effect of [K+]e on Ca2+ inward flow: [K+]e and Ca2+ are thought to compete in the passage through the cell membrane, and it is also thought that a decrease in [K+]e in hypokalemia accelerates repolarization phase 2 Ca2+ inward flow and shortens or eliminates the phase 2 plateau in normal conditions. The accelerated Ca2+ inward flow results in a rapid increase in intracellular calcium concentration ([Ca2+]i ), which increases myocardial contractility via excitation-systole coupling. In hyperkalemia, [K+]e is increased, which slows down the repolarization phase 2 Ca2+ inflow, so the phase 2 plateau can be prolonged. [ Ca2+ ] i does not tend to rise more rapidly, resulting in reduced myocardial contractility.
It is now believed that the rapid and transient repolarization phase 1 is caused mainly by K+ outflow rather than Cl- inward flow. The repolarization phase 2 plateau is caused by an inward flow of Ca2+ and an outward flow of K+ with comparable exchange charges inside and outside the membrane, followed by a faster voltage drop in repolarization phase 3 due to the inactivation of Ca2+ channels mainly forming outward potassium ion flow. As mentioned earlier, the level of [K+]e in repolarization phases 2 and 3 also plays a role in the permeability of the cell membrane to K+.
In hypokalemia, the outflow of potassium is slowed and the inward flow of Ca2+ is accelerated, so the phase 2 plateau is shortened or disappeared, and the phase 3 is prolonged under the condition of slowed potassium outflow.
(1) Characteristics of myocardial electrophysiological changes in hypokalemia.
(1) Autoregulation: Autoregulation depends on the speed of automatic depolarization of autoregulatory cells in phase 4. The decrease in [K+]e in hypokalemia decreases the permeability of the myocardial cell membrane to potassium and reduces the outflow of K+ and increases the inward flow of Na+ or Ca2+ during the phase 4 automatic depolarization of the autoregulatory cells, which accelerates the depolarization and causes an increase in autoregulation.
② Excitability: According to the Nernst equation, in acute hypokalemia, the [K+]i/[K+]e ratio increases and the absolute value of Em should increase. However, as [K+]e decreases, the permeability of the myocardial cell membrane to potassium decreases and the intracellular potassium outflow decreases, resulting in a decrease in the absolute value of Em and a decrease in the Em-Et interval, thus increasing the excitability of the myocardial cells.
(3) Conductivity: The decrease in the absolute value of Em and Em-Et distance in cardiomyocytes slowed down the depolarization speed and magnitude of phase 0, reduced the potential difference between the excitation site and the periphery, and slowed down the spread of excitation, resulting in a decrease in conductivity.
④ Contractility: The contractility of cardiomyocytes is related to the rate of Ca2+ inward flow during phase 2 of the action potential. In hypokalemia, [K+]e decreases and its inhibitory effect on repolarization phase 2 Ca2+ inward flow is reduced, and repolarization phase 2 Ca2+ inward flow is accelerated, resulting in a faster increase in [Ca2+]i and a stronger excitation-contraction coupling process in the myocardium, resulting in higher contractility of the myocardium. However, in severe or chronic hypokalemia, myocardial contractility decreases due to intracellular potassium deficiency, which affects cellular metabolism and causes structural damage to the myocardium.
(2) Electrocardiogram ( ECG ) changes.
① Decreased conduction can cause prolongation of ECG P-R interval and widening of QRS complex waves, reflecting atrioventricular and intraventricular conduction block, respectively.
(2) Accelerated phase 2 Ca2+ inflow promotes transient K+ outflow, causing accelerated repolarization in phase 2, which is manifested as S-T segment depression on ECG.
(3) In phase 3, potassium outflow slows down, which prolongs repolarization phase 3 and prolongs myocardial hyperactivity, causing ECG changes such as T-wave depression, widening and inversion, pronounced U-wave and prolonged Q-T interval.
Among the above ECG changes, depression of the S-T segment and the presence of a distinct U wave after the T wave are the characteristic changes of hypokalemia.
(3) Arrhythmia in hypokalemia.
In hypokalemia, myocardial excitability is increased, the supernormal period is prolonged, and the autoregulation of the ectopic pacing point is increased, while the conduction is slowed and the effective induction period is shortened, which can easily cause excitation folding. Therefore, hypokalemia is prone to premature beats, atrioventricular block, ventricular fibrillation and other arrhythmias.
3. Effects on acid-base balance
Hypokalemia can cause alkalosis by the following mechanisms.
① In addition to hypokalemia caused by abnormal potassium distribution, hypokalemia causes intracellular acidosis and extracellular alkalosis due to intra- and extracellular K+-H+ exchange;
② When blood potassium decreases, intracellular [ K+ ] in the renal tubular epithelium decreases, secretion of K+ decreases, and H+ – Na+ exchange is enhanced. At the same time, ammonia secretion by the renal tubules increases, and is excreted with H+ in the form of NH4+ in urine; potassium deficiency can also reduce chlorine reabsorption by the distal tubule, causing chlorine deficiency in the body, both of which can increase HCO3- reabsorption. In alkalosis caused by hypokalemia, the urine is acidic due to the increase of urine [H+], which is different from the alkaline urine in general alkalosis, so it is also called “paradoxical acidic urine”.
4. Effects on blood vessels
A decrease in potassium may directly cause diastole of small arteries, and may also increase PGE, a vasodilating substance, which may reduce peripheral vascular resistance. Therefore, patients with hypokalemia are prone to vertigo and hypotension.
5. Effects on the kidneys
Chronic hypokalemia can cause a decrease in renal blood flow and glomerular filtration rate, as well as structural and functional changes in various renal tubular segments, such as reduced responsiveness to ADH, impaired NaCl reabsorption in the thick segment of the ascending branch of the medullary loop, and impaired renal concentration, resulting in polyuria, nocturia, and even nephrogenic uremia; increased ammonia production and HCO3- reabsorption in the renal tubules, which is conducive to alkalosis; it may also lead to the occurrence of the so-called “potassium deficiency nephrosis”. The so-called “nephropathy of potassium depletion”, with obvious tubular damage and interstitial fibrosis.
6. Other aspects of the body
In addition to the increase of blood glucose due to the decrease of insulin secretion, the protein synthesis of tissue cells is reduced in hypokalemia. Depending on the degree of potassium reduction, there may be different central nervous system symptoms such as mental ineptness, apathy, unresponsiveness, drowsiness or coma. This is related to factors such as reduced excitability of nerve cells, impaired glucose metabolism, and cell membrane sodium pump dysfunction.
(c) The principles of prevention and treatment of hypokalemia
1.Orally first and then intravenously
2.See urine for potassium supplementation
3, control the amount and speed, intravenous injection is strictly prohibited.