The classification of hypokalemia can be broadly divided into four categories: acute hypokalemia (acute hypokalemia), chronic hypokalemia (chronic hypokalemia), metastatic hypokalemia, and dilutional hypokalemia. (a) Acute hypokalemia, referred to as acute hypokalemia. Due to the increase of potassium loss or combined with insufficient intake, the serum potassium ion concentration drops below the normal level within a short period of time, and the potassium content of the body decreases, making it easy to develop various types of cardiac arrhythmias or muscle weakness. 1. Causes Insufficient intake (1) fasting or anorexia Since both the general diet and the enteral nutrition diet contain more potassium (as mentioned above, most intracellular K+ concentrations are more than 30 times higher than extracellular ones) and the kidneys have a strong potassium retention capacity, the general reduction in diet is not prone to hypokalemia; however, it occurs when there is a serious lack of intake and a lack of potassium in intravenous rehydration, mainly seen in coma, post-surgery, and Patients who are unable to eat or are severely underfed due to digestive tract diseases, etc. Patients with chronic wasting disease, with little muscle tissue and low overall potassium stores, are also prone to hypokalemia when they do not eat enough. Cardiac insufficiency, liver cirrhosis, hematological diseases, tumor diseases, etc. are prone to severe underfeeding. (2) Individual patients with severe eccentricities may also develop hypokalemia. Increased loss is mainly seen in acute loss of various secretory fluids; or in patients with massive diuresis and inadequate potassium supplementation, when it often coexists with hyponatremia and hypochlorhydria. (1) Loss through the digestive tract because the concentration of potassium in all kinds of digestive fluids is almost always higher than that of plasma, and the secretion volume is larger, and the secretion volume is even higher when stimulated by inflammation and other pathological factors; once such diseases occur, the amount of food eaten is significantly reduced, or even completely fasted, so that diseases of the digestive tract are very prone to hypokalemia, and easily combined with other electrolyte ion disorders. The composition of the digestive juices varies from one part of the body to another, so the type of combined electrolyte disorders varies. For example, the gastric juice has a high content of Cl- and H+, so vomiting and gastric drainage can easily be combined with hypokalemia, hypochlorhydria and metabolic alkalosis. The concentration of HCO3- in intestinal fluid is high, so bile duct and pancreatic fluid drainage and diarrhea are easily combined with hyperchloremic acidosis. Hypokalemia can also occur in patients who use laxatives improperly. (2) Loss via the kidney Various primary or secondary renal tubular dysfunction can easily cause excessive potassium loss, and diseases or factors other than the kidney can also increase potassium excretion from the kidney, mainly the following problems. (1) Renal tubular impairment of various causes of proximal or distal tubular acidosis can lead to severe hypokalemia due to decreased reabsorption or increased secretion of potassium. Others such as aminoglycoside antimicrobials, immunosuppressants (especially routinely applied in organ transplant patients), antiviral drugs or chronic potassium or magnesium deficiency tend to impair renal tubular function and hypokalemia occurs. The renal function (creatinine) of these patients is mostly normal or even negative for urine protein, but may be combined with other electrolyte ion deficiencies, uremia, metabolic acidosis, etc. Therefore, it can be called “occult renal tubular impairment”, which is essentially an abnormality of renal tubular reabsorption or secretion function. (2) Hypokalemia occurs during the polyuric phase of renal insufficiency, which is accompanied by the loss of large amounts of electrolytes, such as sodium and potassium. (3) Increased levels or effects of adrenal glucocorticoids or salt corticosteroids have sodium and potassium retention functions, especially the latter, so hypokalemia is likely to occur when its concentration in the blood is increased. Increased secretion: Cortisol and aldosterone have certain similar stimulating factors and production sites (adrenal cortex), and in pathological states, they can be manifested as a separate increase in the level of one hormone or as a simultaneous increase in the level of both hormones. Increased secretion (increased renin secretion is described separately) is mainly seen in: adrenocortical hyperplasia and increased secretion due to hypothalamic and pituitary diseases, adrenocortical adenoma or cancer; stressful increase due to various acute and severe diseases, such as trauma, severe infection, surgery, etc. Exogenous increase: various diseases requiring extensive oral or intravenous application of glucocorticoid therapy. Hypokalemia may also occur in individual patients with inappropriate use of inhaled hormones. Decreased inactivation: seen in cirrhosis and right heart insufficiency. Increased function of the renin-angiotensin-aldosterone system is a relatively common endocrine disorder. Glycocorticoids and their derivatives: Because the receptor structures of salt corticosteroids and glucocorticoids in the distal renal tubule initiation and the cortical collecting duct are very similar, both hormones can bind to each other with both receptors, and the plasma concentration of glucocorticoids is much higher than that of salt corticosteroids and should have a stronger effect, but in fact this is not the case because there is a substance called 11β hydroxysteroid dehydrogenase in these sites that prevents glucocorticoids from Corticosteroids have limited effect on electrolyte metabolism because of the binding of glucocorticoids to the salt corticosteroid receptor, and glycoconjugates can block this binding, leading to a salt corticosteroid-like effect and producing hypokalemia. Diuretics: These include tab diuretics such as tachyphylaxis and thiazide diuretics such as dihydrocortisone, and osmotic diuretics such as mannitol and hypertonic glucose, all of which can lead to large excretion of urinary potassium. (5) Excessive anion in the renal tubule: it increases the negative charge in the tubular lumen and facilitates the secretion of K+, such as the application of high-dose penicillin, especially when combined with blood volume deficiency. ⑥Other: such as hypomagnesemia, Bartter syndrome, cotton phenol poisoning, etc. 2. Pathophysiology and clinical manifestations (1) Nerve-muscle system ① Skeletal muscle weakness and paralysis: hypokalemia, increased concentration difference of K+ inside and outside the cell, increased negative value of resting potential, increased value of trigger domain of action potential, decreased excitability and conductivity of nerve-muscle, and muscle weakness. Muscle weakness usually starts in the lower extremities, especially in the quadriceps, and manifests as difficulty walking and unstable standing; as hypokalemia increases, muscle weakness worsens and involves the trunk and upper extremity muscles until it affects the respiratory muscles and respiratory failure occurs. In general, muscle weakness can occur when the serum potassium concentration is below 3 mmol/L, and paralysis can occur when it is below 2.5 mmol/L. It is also easy to complicate respiratory failure. In patients with pulmonary insufficiency, hypokalemia leading to respiratory failure or aggravation of respiratory failure is more common, but is easily overlooked clinically. (2) Smooth muscle weakness and paralysis: manifested by abdominal distension, constipation, and in severe cases, paralytic intestinal obstruction, and also urinary retention. (2) Circulatory hypokalemia can lead to dysfunction of cardiac muscle cells and their conduction tissues, as well as multiple, small focal necrosis of the myocardium, mononuclear and lymphocyte infiltration, and finally scar formation. ① Arrhythmia: It is related to the abnormalities of excitability of autonomic cardiac cells and conduction tissue conduction, mainly manifested as decreased excitability of sinus node, slowed conduction of atrioventricular junctional zone, and increased excitability of ectopic rhythm cells, so a variety of arrhythmias can occur, including sinus bradycardia, premature atrial or ventricular beats, supraventricular tachycardia and atrial fibrillation, atrioventricular block, and even ventricular tachycardia and ventricular fibrillation. Susceptibility to digitalis toxicity. Electrocardiographic manifestations are valuable in the diagnosis of hypokalemia. As hypokalemia worsens, P-wave widening, QRS wave widening and the above-mentioned arrhythmias may appear. (ii) Cardiac insufficiency: Changes in myocardial function and structure caused by severe hypokalemia may directly induce or aggravate cardiac insufficiency, especially in patients with poor underlying cardiac function. (③) Hypotension: It may be related to vasodilatation due to phytonadic dysfunction. (3) In transverse myelolysis, under normal conditions, K+ is released from the transverse muscle during muscle contraction and the blood vessels dilate to accommodate the increased energy metabolism. In patients with severe hypokalemia, the above effects are diminished, muscle tissue is relatively ischemic and hypoxic, and rhabdomyolysis can occur, with a large amount of myosin entering the renal tubules, which can induce acute renal failure. When the serum potassium concentration is lower than 2.5 mmol/L, there is a possibility of rhabdomyolysis. (4) The main pathological changes of renal impairment are renal tubular hypofunction, epithelial cell degeneration, renal interstitial lymphocyte infiltration, and in severe cases, fibrous changes. Clinical manifestations are: (1) reduced sodium pump activity of renal tubular epithelial cells, reduced intracellular K+, increased hydrogen-sodium exchange, acidic urine, and metabolic alkalosis; increased intracellular Na+, reduced tubular fluid Na+ reabsorption, and hyponatremia. (ii) Decreased concentration function: polyuria, increased nocturia, low specific gravity urine, hypotonic urine, poor response to antidiuretic hormone. ③Increased ammonia production capacity, increased acid excretion, increased HCO-3 reabsorption, and metabolic alkalosis. (iv) Chronic hyperalgesia. It is more common in patients with chronic, long-term hypokalemia or hypomagnesemia. (5) Digestive system mainly leads to hypotonia of smooth muscle of gastrointestinal tract, prone to loss of appetite, nausea, vomiting, abdominal distension, constipation, and even intestinal paralysis. (6) In acid-base and other electrolyte disorders hypokalemia, sodium pump activity is weakened, active transport of ions inside and outside the cell is reduced (passive diffusion is relatively increased), hydrogen-sodium exchange ratio exceeds potassium-sodium exchange, and decreased serum Na+ concentration or hyponatremia, extracellular alkalosis, increased intracellular Na+ concentration and acidosis occur. As mentioned above, the sodium pump activity of renal tubular epithelial cells is weakened, aggravating alkalosis and hyponatremia; ammonia production capacity is increased, further metabolic alkalosis with a corresponding decrease in chlorine retention capacity, and lower blood chloride occurs. It should be emphasized that the effect of K+ on the body is also related to the lack of sodium. When sodium and potassium are lacking at the same time, the symptoms of potassium deficiency are mild; however, when potassium deficiency and sodium intake is normal, the symptoms of potassium deficiency are more obvious. If potassium is deficient while the sodium content of the body is normal, K+ transfers to the extracellular area and Na+ to the intracellular area, leading to intracellular ion disorder, which directly affects the metabolism of the body; Na+ transfers to the intracellular area, which can lead to intracellular edema; K+ and Na+ transfers in large amounts lead to a serious imbalance in the ratio of intra- and extracellular K+ and intra- and extracellular Na+, which directly affects the resting potential and action potential, resulting in obvious clinical symptoms. However, when Na+ and K+ are lacking at the same time, the intra- and extracellular ion transfer is not obvious, and the effect on cell metabolism and electrophysiology is not significant instead. Therefore, the sodium intake should be strictly controlled in severe hypokalemia. (1) Commonly used blood test indexes include decreased serum potassium concentration, less than 3.5mmol/L, blood pH at normal high limit or greater than 7.45, Na+ concentration at normal low limit or less than 135mmol/L. (2) Commonly used urine test indexes include decreased urinary potassium concentration (except for renal tubular impairment or “occult renal tubular impairment”) and urinary pH deviation. ” except), urinary pH is acidic, urinary sodium excretion is high. 4. Treatment (1) Principles Acute hypokalemia mostly has clear underlying disease or predisposing factors, especially more medical factors, so prevention should be the main focus. First of all, we should try to get rid of the causative factors and resume normal diet as soon as possible. Since food contains a large amount of potassium salts, as soon as the patient resumes a normal diet and tries to correct the large amount of potassium loss. In the case of temporary failure to correct a large amount of potassium loss, potassium should be appropriately supplemented and hypokalemia will be easily prevented and treated. (2) The amount of supplementation Once acute hypokalemia occurs, rehydration in proportion to the body fluid electrolytes is sufficient. The amount of potassium supplementation (mmol) = (4.2 – measured value) x body weight (kg) x 0.6 + continued loss + physiological requirements. Since it takes about 15h for the exchange of potassium inside and outside the cells to reach equilibrium, the general rule is to replenish 2/3 on the first day and 1/3 on the next day, and the speed of replenishment should be controlled, faster at the beginning and slower thereafter, so that the fluid is inputted more evenly within 24h, and reviewed once in 2 to 6h if necessary. Generally choose potassium chloride solution. After the blood K+ concentration is normalized, it is still necessary to supplement potassium chloride solution for several days. (3) Precautions As mentioned before, after giving glucose rehydration solution, because it can stimulate the secretion of insulin, accompanied by the allogenic effect of glycogen (bound potassium), it can lower the serum potassium concentration; when giving saline or sodium bicarbonate rehydration solution, the sodium concentration of both extracellular and intracellular fluid increases, activating Na+-K+-ATPase, which causes potassium to be transported into the cells and lowering the blood potassium. Therefore, in the treatment of hypokalemia, if potassium salts are given intravenously in 5% or 10% glucose solution (sugar concentration is significantly higher than blood glucose concentration) or saline (sodium concentration is higher than blood sodium concentration), the potassium concentration may be temporarily lowered if the infusion is too fast. 5% sugar saline as a common rehydration solution may worsen the hypokalemia through the dual transport of K+ by glucose and Na+. Special attention is needed. In patients with oliguria or anuria, potassium supplementation is generally not indicated, except in severe hypokalemia, because serum potassium concentration can increase by 0.3 mmol/L after 1 day of anuria. (4) Oral potassium-preserving diuretics such as anisodone or aminoglutethimide can help recovery from hypokalemia. (5) Oral ACE inhibitors such as Kepone preserve potassium by inhibiting the production of aldosterone. In general, the application of ACE inhibitors has a major difference in the regulatory effect on the kidneys and the systemic hypotensive effect, with the former requiring significantly smaller doses than the latter. The combination of potassium-preserving diuretics, ACE inhibitors and potassium is the strongest theoretical combination to raise blood potassium and has a certain regulatory effect on renal function, which has a high promotion value, but attention should be paid to regular rechecking of blood potassium to avoid hyperkalemia. (6) Potassium supplementation In patients with mild hypokalemia, oral potassium chloride solution should be the mainstay, about 3g per day, and the same dose can be given for intravenous application if it cannot be taken orally. In patients with moderate hypokalemia, both oral and intravenous applications should be given, about 6 g/day. in severe patients, both potassium chloride and potassium glutamate should be given, about 9 g/day. If the serum K+ concentration is at the low limit of normal (3.5 to 4.0 mmol/L) and the dynamic follow-up shows a decreasing trend, it often means that the body is potassium deficient, especially in the elderly or in patients treated with digitalis, and must be supplemented with potassium. (7) Treatment of severe hypokalemia Our treatment experience is to add 15ml of 10% potassium chloride to 500ml of 5% glucose solution intravenously, 1000-1500ml daily; 20-40ml of 31.5% potassium glutamate to 500ml of 5% glucose solution, 500-1000ml daily; 30-40ml of oral potassium chloride daily, divided into 3-4 times Orally, the blood potassium is rechecked once around 2h, with an increase of 0.1~0.3mmol/L each time until normal. Patients who need to strictly control the amount of fluid intake can choose deep vein placement to increase the concentration, reduce the amount of water intake and use micro-pump. If the blood K+ concentration continues not to rise or even decreases, an indwelling intravenous catheter is also an option to increase the potassium concentration and to monitor the electrocardiogram. Patients in this category also need to apply potassium-protective diuretics and ACE inhibitors at the same time, avoid Na+ input or intake, and avoid the simultaneous application of large amounts of glucose, amino acids and insulin. (2) Chronic potassium-deficit hypokalemia (chronicpotassium-deficithypokalemia) refers to the gradual decrease of serum potassium ion concentration below the normal level due to increased potassium loss or combined with insufficient intake, and the decrease of potassium content in the body. Because of the slow onset and mild degree of compensation and adaptation, the clinical symptoms are mild, with weakness, loss of appetite, polyuria and insidious damage to the renal tubules as the main manifestations (see acute potassium loss hypokalemia for details). The principles of treatment are similar to those of acute hypokalemia and will not be repeated. However, since this group of patients has certain adaptations and compensations, it is emphasized that the rate of potassium supplementation does not need to be too fast, and that an increase in blood K+ concentration of 0.2 to 0.4 mmol/day is generally sufficient. In moderate and severe hypokalemia Na+ intake or input should be avoided, otherwise it will lead to persistent transfer of K+ into the cells and persistent excretion via the renal tubules, and recalcitrant hypokalemia will occur. Due to the long onset of the disease, the body’s potassium level is significantly reduced, while the kidney’s ability to reabsorb potassium is reduced. Therefore, potassium chloride supplementation should be continued for about a week or even longer after the blood K+ concentration is normalized, so that the body’s potassium level is eventually normalized. In addition, chronic hypokalemia is often accompanied by magnesium and phosphorus deficiency, while phosphorus and Mg2+ deficiency often lead to a decrease in sodium pump activity and cellular metabolic disorders, resulting in a decrease in intracellular potassium concentration and a decrease in the kidney’s ability to reabsorb K+. ). Insufficient water-soluble vitamins in the body due to poor diet or inadequate supplementation can also lead to a weakening of the sodium pump activity and chronic hypokalemia. It is also important to emphasize that K+ may continue to be lost during the course of treatment, so the actual amount of supplementation should be increased, especially in patients with “occult renal tubular impairment” (chronic hypokalemia itself can lead to tubular dysfunction and organic damage). Patients whose blood potassium does not rise significantly after potassium supplementation should be routinely checked and followed up with urine electrolytes and other electrolyte ion and water-soluble vitamin supplements. Chronic hypokalemia often leads to reduced sodium pump activity in somatic cells and metastatic hyponatremia; reduced sodium pump activity in renal tubular epithelial cells and increased renal sodium excretion aggravate hyponatremia, so patients with chronic hypokalemia combined with hyponatremia should focus on correcting hypokalemia. (iii) Shifted hypokalemia (shiftedhypokalemia) is hypokalemia caused by potassium ions entering the cells, mainly seen in patients with periodic paralysis, various causes of alkalosis or insulin application. It is mainly divided into two conditions as follows. 1. Primary significant enhancement of the sodium pump function results in rapid entry of K+ into the cells, leading to hypokalemia, mainly seen in periodic paralysis and unexplained hypokalemia. It is characterized by a rapid progression of the disease with obvious clinical symptoms and no change in the body’s K+ content. the transfer of K+ into the cell is inevitably accompanied by the transfer of Na+ into the cell, while the transfer of H+ into the cell is reduced, with mild hypernatremia and mild metabolic acidosis, and the acidosis leads to a compensatory increase in Cl- concentration. This is the exact opposite of potassium deficiency hypokalemia leading to extracellular metabolic alkalosis and hyponatremia and is worth noting. The principles of treatment are: ① Avoid K+ transfer or increased excretion due to glucose, if hypertonic sugar is not used, choose 5% glucose solution, and when rehydration is rapid, establish a deep venous line to increase the potassium concentration and infuse with a micropump. ②As the increase of Na+ concentration can promote the transfer and excretion of K+ and aggravate hypokalemia, it is necessary to avoid the simultaneous application of various forms of sodium chloride solution, as saline and 5% sugar saline are often used inadvertently, special attention should be paid. (iii) Excessive Cl- intake should also be avoided due to compensatory increase in Cl- concentration. Therefore, potassium chloride should not be supplemented too much and can be supplemented with potassium glutamate at the same time. Since this type of hypokalemia occurs very fast and the transfer of potassium is mostly still going on during the treatment, there are more chances of respiratory muscle weakness, respiratory failure and cardiac arrhythmia, and the treatment should be especially aggressive. 2. Transferred hypokalemia due to other causes is more common clinically, mainly in patients with increased ventilation from various causes, alkalosis, or the application of insulin, hypertonic sugar, or amino acids. Increased ventilation from various causes, such as fever, pulmonary edema, pneumonia and other site infections, trauma, and acute respiratory distress syndrome can lead to respiratory alkalosis and acute hyperkalemia. Since patients have high catabolism and K+ release from the cells, hypokalemia is not serious and should be treated mainly by treating the original disease and reducing ventilation. In a small number of patients, the blood K+ concentration decreases significantly, so potassium should be supplemented appropriately. Mechanical ventilation for chronic respiratory failure is one of the most important causes of chronic metastatic hypokalemia. The main therapeutic measure at this time should be to rapidly and substantially reduce the ventilation volume, which is generally 1/3 to 1/2 or even greater, with the main focus on slowing down the respiratory rate. In patients with chronic acidosis and normal blood K+ concentration, there is a true lack of potassium in the organism, so the improvement of acidosis is often accompanied by hypokalemia. pH increases by 0.1 and blood K+ concentration decreases by about 0.1 mmol/L. Therefore, the principle of treatment is to control the speed of improvement of acidosis, and at the same time, supplement potassium chloride and potassium glutamate appropriately to avoid alkalosis. Once alkalosis occurs, measures should be taken to bring down the pH appropriately. However, avoid applying arginine hydrochloride, because it can quickly enter the cell through the cell membrane, aggravate the intracellular acidosis and further affect the cell metabolism. The stability of the intracellular environment is the basis of normal cell metabolism, and its role is much more important than that of the extracellular environment (i.e., the “internal environment” of the body), so clinicians should pay more attention to the electrolyte disorders of the “intracellular environment” than just the “internal environment” of the body. Therefore, clinicians should pay more attention to the electrolyte disorders in the “intracellular environment” than just the disorders in the “internal environment” of the body. During the improvement of diabetic ketoacidosis, stress hyperglycemia or other conditions of hyperglycemia, severe hypokalemia can occur due to the dual effect of pH increase and insulin. Other factors, such as the application of catecholamine preparations, can also activate sodium pump activity and lead to hypokalemia, but to a lesser extent and with less clinical value. In the acute phase of various wasting diseases or critical illnesses, due to the vigorous cellular catabolism and intracellular K+ release, the renal elimination also increases in order to keep the blood K+ concentration normal, leading to potassium deficiency in the organism. In the process of disease improvement, hypokalemia can occur due to enhanced anabolic metabolism, so the daily requirement of potassium increases accordingly. Of course other electrolyte ions, water-soluble vitamins, energy and protein supplements should also be increased. (iv) Dilutional hypokalemia (dilutional hypokalemia) is hypokalemia caused by an increase in blood volume or extracellular fluid volume, accompanied by dilutional hyponatremia. There is usually a limited decrease in blood potassium. Treatment should be based on strict control of water intake and appropriate diuresis on the basis of potassium chloride and sodium chloride supplementation.