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How is hypokalemia caused?
(A) the cause of the disease

1. potassium intake decreased.

The general diet is rich in potassium. Therefore, as long as you can eat normally, the body will not be short of potassium. Patients with digestive tract obstruction, coma and fasting for a long time after operation cannot eat. Potassium deficiency and hypokalemia can be caused if potassium is not supplemented at the same time or is not enough when intravenous nutrition is given to these patients. However, if insufficient intake is the only reason, the degree of potassium deficiency in a certain period of time can not be very serious because of the potassium preservation function of the kidney. When potassium intake is insufficient, urinary potassium excretion can be reduced to less than 20mmol/L within 4 ~ 7 days, and to 5 ~10 mmol/L within 7 ~10 days (normal urinary potassium excretion is 38 ~150 mmol/L).

2. Excessive potassium excretion

(1) Potassium loss through gastrointestinal tract: This is the most important cause of potassium loss in children, and it is common in patients with severe diarrhea and vomiting accompanied by a large amount of digestive juice loss. The concentration of K+ in feces can reach 30 ~ 50 mmol/L during diarrhea. At this time, the potassium lost with feces can be more than normal10 ~ 20 times. The reason why fecal potassium content increases is that on the one hand, the absorption of potassium in the small intestine is reduced because of diarrhea, and on the other hand, the reduction of blood volume caused by diarrhea can increase aldosterone secretion, and aldosterone can not only increase urinary potassium excretion, but also strengthen the role of colon in secreting potassium. Because the potassium content of gastric juice is only 5 ~10 mmol/L, the loss of gastric juice is not the main reason for potassium loss during severe vomiting, but a large amount of potassium is lost through kidney and urine, because metabolic alkalosis caused by vomiting can increase renal potassium excretion (see later), and the reduction of blood volume caused by vomiting can also promote renal potassium excretion through the increase of secondary aldosterone.

(2) Renal potassium loss: This is the most important reason for potassium loss in adults. Common factors causing increased renal potassium excretion are:

① Long-term continuous use or excessive dosage of diuretics: for example, diuretics that inhibit sodium and water reabsorption in proximal convoluted tubules (carbonic anhydrase inhibitor acetazolamide) and diuretics that inhibit the reabsorption of Cl- and Na+ in ascending branches of medullary loop (furosemide, uric acid, thiazides, etc.) can increase the flow of raw urine reaching distal renal tubules, and the increase of flow here is an important reason for promoting the increase of potassium secretion in renal tubules. The above diuretics can also increase the amount of Na+ reaching the distal convoluted tubule, which leads to potassium loss through the strengthening of Na+-K+ exchange. Many diuretics also have the same mechanism of increasing renal potassium excretion: the decrease of blood volume leads to the increase of aldosterone secretion. The effects of furosemide, uric acid and thiazide are to inhibit the reabsorption of Cl- by the thick segment of ascending branch of medullary loop, thus inhibiting the reabsorption of Na+. Therefore, the long-term use of these drugs can lead to both hyponatremia and hypochloremia. It has been proved that hypochloremia caused by any reason can increase renal potassium excretion. One of the possible mechanisms is that hypochloremia seems to directly stimulate the potassium secretion function of distal renal tubules.

② Some kidney diseases, such as distal tubular acidosis, due to the dysfunction of hydrogen secretion in distal convoluted tubules, the exchange of H+-Na+ decreases and the exchange of K+-Na+ increases, resulting in potassium loss. In proximal renal tubular acidosis, the reabsorption of HCO3- in proximal convoluted tubule decreases, and the increase of HCO3- in distal convoluted tubule is an important reason for promoting the increase of potassium excretion in distal convoluted tubule (see details later). In the polyuria stage of acute renal tubular necrosis, due to the osmotic diuresis caused by the increase of urea in renal tubular fluid and the insufficient function of new renal tubular epithelium to reabsorb water and electrolyte, potassium excretion may increase.

③ Hyperadrenocortical hormone: During primary and secondary aldosteronism, Na+-K+ exchange between renal distal convoluted tubule and collecting duct increases, thus playing the role of removing potassium and preserving sodium. In Cushing syndrome, the secretion of glucocorticoid cortisol is greatly increased. Cortisol also has a certain mineralocorticoid-like effect. A large and long-term increase in cortisol can also promote Na+-K+ exchange between distal convoluted tubules and collecting ducts, resulting in an increase in renal potassium excretion.

④ The number of anions that are not easily reabsorbed in the distal convoluted tubule increases: HCO3-, SO42-, HPO42-, NO3-, β-hydroxybutyric acid, acetoacetic acid and penicillin. When they increase in the distal convoluted tubule fluid, they can not be reabsorbed and increase the negative charge of the original urine, so K+ easily enters the lumen fluid from the renal tubular epithelial cells and is lost with urine.

⑤ magnesium deficiency: magnesium deficiency often causes hypokalemia. The potassium reabsorption of ascending branch of loop of medulla oblongata depends on Na+-K+-ATR enzyme in renal tubular epithelial cells, which needs the activation of Mg2+. When magnesium is deficient, the enzyme may be inactivated due to the loss of Mg2+ in the cell, so the potassium reabsorption in this area is hindered and potassium is lost. Animal experiments have also proved that magnesium deficiency can also cause aldosterone increase, which may also be the cause of potassium loss.

⑥ Alkalosis: During alkalosis, the excretion of H+ in renal tubular epithelial cells decreases, so the exchange of H+-Na+ is strengthened, so the excretion of potassium increases with urine.

(3) Transdermal potassium loss: The potassium content in sweat is only 9mmol/L.. In general, sweating does not cause hypokalemia. However, when heavy physical labor is carried out in a high temperature environment, excessive sweating can also lead to the loss of potassium.

3. Extracellular potassium is transferred to the cell. Hypokalemia can occur when extracellular potassium is transferred to the cell, but the total amount of potassium in the body does not decrease.

(1) Hypokalemic periodic paralysis: Extracellular potassium shifts to intracellular during the attack, which is a family disease.

(2) alkalosis: intracellular H+ moves to extracellular to compensate, while extracellular K+ enters the cell.

(3) Excessive insulin: When high-dose insulin is used to treat diabetic ketoacidosis, there are two mechanisms for hypokalemia:

① Insulin promotes cell glycogen synthesis, which requires potassium, and plasma potassium enters cells with glucose to synthesize glycogen.

② Insulin may directly stimulate Na+-K+-ATPase in skeletal muscle cell membrane, thus increasing Na+excretion in muscle cells and K+entry into muscle cells.

(4) Barium poisoning: During War of Resistance against Japanese Aggression's period, a large number of cases of "paralysis" occurred in a certain place in Sichuan, the clinical manifestations were mainly muscle weakness and paralysis, and severe cases often died of respiratory muscle paralysis. Through the research of Chinese scholar Du Gongzhen, it is determined that the cause of the disease is barium poisoning. However, the mechanism of paralysis caused by barium poisoning was not yet clarified. It has been confirmed that the mechanism of paralysis caused by barium poisoning is that barium poisoning causes hypokalemia. When barium is poisoned, Na+-K+-ATPase on cell membrane continues to move. Therefore, potassium in extracellular fluid keeps entering cells. However, the channels through which potassium flows out of cells are specifically blocked, resulting in hypokalemia. Barium poisoning is caused by some acid-soluble barium salts such as barium acetate, barium carbonate, barium chloride, barium hydroxide, barium nitrate and barium sulfide.

4. Crude cotton oil poisoning In recent twenty or thirty years, a hypokalemic paralysis has appeared in some cotton producing areas in China, and it is also called "soft disease" in some provinces. Its main clinical feature is that the muscles of limbs are extremely weak or flaccid paralysis occurs, and severe cases often die of respiratory muscle paralysis, and the serum potassium concentration is obviously reduced. Often many people get sick in the same area. The etiology is closely related to the consumption of crude cottonseed oil. Crude cotton oil is produced by some small oil plants and mills in rural areas. The production technology of these factories is not up to standard. Cottonseed was used to extract oil without full steaming or even shelling, and the extracted oil was not refined by adding alkali as required. Therefore, many toxic substances in cottonseed are stored in oil. Gossypol is related to the occurrence of "soft disease" and a series of subsequent studies. The mechanism of hypokalemia in "soft disease" has not been clarified. The discovery of "soft disease" and a series of subsequent studies were all carried out by Chinese scholars. So far, there is no record of this disease in foreign books and periodicals.

(2) Pathogenesis

The physiological function of K has been described above. When intracellular potassium is deficient in extracellular potassium and acidosis occurs, if intracellular K decreases, the K exchanged with extracellular H decreases, so potassium deficiency is often accompanied by metabolic acidosis. Chronic potassium deficiency can be seen in potassium-deficient nephropathy, which mainly shows renal tubular insufficiency. The decrease of blood potassium can also increase the resting potential of myocardial cells and prolong the time of action potential, which is reflected in the decrease of ST segment, the decrease of T wave amplitude, flattening or inversion, the appearance of U wave and its fusion with T wave on ECG. Due to the decrease of intracellular K, the increase of the autonomy of cardiac pacemaker cells and the inhibition of myocardial conduction, it is easy to produce new ectopic excitation focus and cause various arrhythmia, and in severe cases, ventricular fibrillation leads to death. Atrioventricular block may also occur.