Mixed tubular acidosis

　　One, etiology of the disease

　　Mixed type RTA is characterized by the coexistence of clinical features of both type I and II RTA, so the etiology also has the characteristics of type I and II RTA.

　　1. Primary diseases scattered and hereditary.

　　2. Secondary genetic diseases osteosclerosis, neurosensory hearing loss, carbonic anhydrase B deficiency or decreased function, deficiency of pyruvate hydroxylase, decreased hereditary fructose tolerance, cystinosis, Lowe syndrome, Wilson's disease, etc.

　　3. Drugs and poisoning amphotericin B, lithium, toluene.

　　4. Abnormal calcium metabolism primary calcium deposition nephropathy, idiopathic hypercalcemia, vitamin D overdose or poisoning, hyperthyroidism, hyperparathyroidism.

　　5. Systemic immune diseases and hypergammaglobulinemia idiopathic hypergammaglobulinemia, multiple myeloma, systemic lupus erythematosus, Sjögren's syndrome, thyroiditis, liver cirrhosis, primary biliary cirrhosis, chronic active hepatitis.

　　6.Interstitial kidney disease obstructive nephropathy, renal transplant rejection, sickle cell hemoglobinopathy, cavernous kidney, analgesic nephropathy.

　　7. Primary diseases scattered and hereditary.

　　8. Secondary genetic diseases decreased hereditary fructose content, carbonic anhydrase B deficiency and decreased function.

　　9. Drugs and heavy metals (lead, cadmium, mercury, copper), carbonic anhydrase inhibitors, taking expired tetracycline.

　　10. Other hyperparathyroidism, multiple myeloma, Sjögren's syndrome, amyloidosis, nephrotic syndrome, renal transplant rejection, hypercalcemia, chronic active hepatitis.

　　Second, pathogenesis

　　The pathogenesis of mixed type RTA should be similar to that of type I and II RTA.

　　1. Decreased active transport of H+ to the lumen.

　　(1) Defect in gradient: The H+ transport is abnormally sensitive to the inhibitory effect of luminal H+ (lumen-cell or lumen-peritubular H+ gradient), and its active transport speed is reduced.

　　(2) Defect in H+ secretion: Even after the inhibition of H+ concentration is relieved, the transport of H+ from the cell to the lumen is still lower than normal, and the secretory ability is reduced.

　　2. Increased diffusion rate of H+ from the lumen to the cell (or to the interstitium).

　　(1) Increased H+ reflux: The luminal membrane of the tubular epithelial cells or the tight junctions have increased permeability to H+, causing H+ to reflux from the lumen into the cell.

　　(2) Defect in voltage-dependent H+ transport: Due to reduced luminal Na+ absorption or increased Cl- reabsorption, the negative charge of the lumen is reduced, leading to decreased H+ secretion or increased H+ reflux.

　　3. Decreased ability to reabsorb HCO3-: Normally, 85% of HCO3- is reabsorbed in the proximal tubule. When the acidification function of the proximal tubule is damaged, the ability to reabsorb HCO3- decreases, and excessive HCO3- is excreted in the urine. This loss of bicarbonate causes the blood HCO3- content to decrease, forming acidosis and alkaline urine.

　　Metabolic acidosis, hypokalemia, rickets, delayed growth and development, vitamin D deficiency disease or osteomalacia, some may develop kidney stones or renal calcification, and in the late stage, it may develop into uremia, and a few may have neurosensory hearing loss, etc.

　　1. Metabolic acidosis is the most common type of acid-base imbalance, caused by an increase in extracellular H+ or loss of HCO3-, leading to primary decrease in HCO3-.

　　2. Serum potassium concentration below 3.5 mmol/L (3.5 mEq/L, the normal range of serum potassium concentration in healthy people is 3.5～5.5 mmol/L) is called hypokalemia. In hypokalemia, the total potassium content in the body may not necessarily decrease. This is the case when extracellular potassium is transferred to intracellular potassium. However, in most cases, patients with hypokalemia also have a decrease in the total potassium content in the body - potassium deficiency.

　　3. Vitamin D deficiency disease (vitamin D deficiency) is caused by factors such as insufficient sunlight exposure (ultraviolet light照射 on the skin can convert vitamin D precursors into effective vitamin D), insufficient intake (milk, eggs, liver, fish, and other foods), absorption disorders (intestinal diseases), and increased demand (children, pregnant women, lactating mothers), leading to insufficient vitamin D in the body and systemic calcium and phosphorus metabolism disorders and skeletal changes.

　　4. Kidney stones (calculus of kidney) refer to stones occurring in the renal pelvis, calyces, and the junction of the renal pelvis and ureter. Most are located within the renal pelvis and calyces, and renal parenchymal stones are rare. Radiographs show single or multiple round, oval, or obtuse triangular dense shadows in the renal area, with high and uniform density and smooth edges, but they can also be rough and appear like mulberries.

　　Uremia actually refers to the inability of the human body to produce urine through the kidneys, to excrete waste products and excessive water from the body's metabolism outside, causing harm.

　　The typical clinical manifestations of mixed RTA include:

　　1. There is often acidosis

　　Typical cases may have hyperchloremic acidosis, with urinary pH able to drop below 5.5, or have diabetes, phosphaturia, aminoaciduria, and other conditions.

　　2. Clinical manifestations of hypokalemia

　　Secondary hyperaldosteronism promotes the excretion of K+, and metabolic acidosis with low sodium and low potassium levels can lead to growth and development delays, nausea, vomiting, and other symptoms of acidosis, as well as weakness, fatigue, muscle weakness, and constipation due to low sodium and low potassium levels.

　　3. Urinary system stones.

　　4. Bone disease

　　The occurrence of bone disease is more common in patients with type I RTA than in those with mixed RTA. Children may present with vitamin D deficiency disease, while adults may have osteosclerosis.

　　5. Secondary hyperparathyroidism

　　Some patients have reduced urinary phosphorus excretion, leading to decreased blood phosphorus levels and secondary hyperparathyroidism.

　　There is no effective preventive measure for type III renal tubular acidosis. Prevention of secondary diseases should start with the treatment of the underlying disease, controlling its progression to tubular acidosis. Patients with the disease should be treated actively to prevent the progression of the disease and strive for a good prognosis.

　　1. The blood test mainly shows low levels of blood K+, Ca2+, Na+, and PO43-, increased blood Cl-, decreased plasma HCO3-, and reduced CO2 binding power. Elevated blood chloride, decreased blood HCO3-, and normal or decreased blood potassium levels.

　　2. Urinalysis shows that there are no cellular components in the urine, the HCO3- excretion fraction is increased by 5.5, and the urinary potassium excretion increases.

　　3. Load test

　　(1) Ammonium chloride test: It is a common test for suspected and incomplete type I RTA; give the subject 0.1g/(kg·d) of ammonium chloride, taken orally in three divided doses, for three consecutive days. On the third day, urine is collected every hour, and urine pH and blood HCO3- are measured. When the blood HCO3- decreases to below 20mmol/L while the urine pH is > 5.5, it has diagnostic value. For patients with liver disease, calcium chloride 1mmol/(kg·d) is used instead, and the method and positive result judgment are the same as the ammonium chloride load test.

　　(2) Urinary ammonium determination: The urinary excretion amount of ammonium in normal people is about 40mmol/d, the urinary excretion amount of ammonium in type I RTA

　　(3) Urinary PCO2 measurement: 5% sodium bicarbonate intravenous infusion, maintain blood pH above 0.5h; when urine pH > blood pH, urine PCO2 > blood PCO2 2.66kPa or more has diagnostic significance. That is, once the urine becomes alkaline, regardless of whether the blood HCO3- concentration has returned to normal, if urine PCO2 > 9.3kPa, it can be considered that the secretion ability of H+ in the collecting ducts is normal.

　　(4) Urinary cysteine test: Cysteineuria often exists in proximal tubule disease, and a positive result is helpful for diagnosis (cyanide nitroprusside test: take 5ml of urine and add 1 drop of concentrated ammonia water, 3 drops of 5% sodium cyanide, and a purple-red reaction is positive). In the acid load test, if the urine pH

　　(5) Alkaline load test:

　　① Oral sodium bicarbonate method: Starting from 1mmol/(kg·d), the dosage is increased day by day to 10mmol/(kg·d), after the acidosis is corrected, the blood and urine HCO3- concentration and glomerular filtration rate are measured, and the percentage of urine HCO3- is calculated: the amount of HCO3- in urine = urine HCO3-(mmol/L) × urine volume (ml/min) / plasma HCO3-(mmol/L) × GFR. The normal urine HCO3- is zero; type II, mixed type RTA > 15%, type I RTA glomerular filtration amount 15%, indicating that there is a barrier to the absorption of HCO3- in the proximal tubule. Urine HCO3- excretion fraction = (urine HCO3-/plasma HCO3-) / (urine creatinine / blood creatinine). When the plasma HCO3- concentration is normal, the HCO3- excretion fraction of type II RTA is > 15%, and type I RTA

　　4. In the KUB flat film or IVP film of imaging examination, fish roe-like renal calculi can be found. And it can understand the condition of bone disease.

　　5. Ultrasonic examination can understand whether there is calcification and calculus in the kidneys.

　　What is not suitable to eat for patients with mixed type renal tubular acidosis:

　　1. Foods that are easy to raise blood sugar rapidly: sugar, brown sugar, rock sugar, glucose, maltose, honey, chocolate, sugar candy, fruit candy, candied fruits, canned fruits, soda, fruit juice, sweet beverages, jam, ice cream, sweet biscuits, cakes, sweet bread and sugar-coated desserts, etc.

　　2. Foods that easily raise blood lipids: butter, mutton fat, lard, butter, cream, fatty meat. For foods rich in cholesterol, special attention should be paid, and they should not be used or used less.

　　I. Treatment

　　The treatment of mixed type renal tubular acidosis and type III renal tubular acidosis should refer to types I and II. But the dosage of alkaline drugs for type III should be larger, and the dose of sodium bicarbonate is 5-10 mmol/kg per day. The treatment is the same as type I RTA for those similar to type I RTA.

　　1. Treatment of etiology Type I RTA patients often have etiology, and if the etiology can be treated, the potassium and acid secretion disorders can be corrected.

　　2. The application of alkaline drugs The dose of alkaline drugs for type I RTA should be relatively small, and a large dose can cause convulsions. Because the liver can convert sodium citrate into sodium bicarbonate, a compound citrate mixture, that is, Shohl solution (140g of citric acid, 98g of sodium citrate, and water to 1000ml), 50-100ml/d, divided into 3 times for oral administration is often given.

　　3. Treatment of potassium disorder Patients with hypokalemia commonly use potassium citrate mixture, that is, 300g of sodium citrate, 200g of potassium citrate, and 1800ml of water; 60ml/d, divided into 3 times for oral administration. Potassium supplementation should also start with a small dose and gradually increase. Potassium chloride should not be used.

　　4. The application of calcium and vitamin D The dosage of vitamin D is relatively large, 300,000 U of vitamin D2 or D3 is injected daily. When blood calcium is greater than 2.5 mmol/L or serum alkaline phosphatase returns to normal, stop using it to avoid hypercalcemia; vitamin D must be used with alkaline drugs. The treatment is the same as type II RTA for those similar to type II RTA.

　　If there are obvious secondary causes such as treatment drugs or metal poisoning, multiple myeloma, nephrotic syndrome, interstitial tubulointerstitial disease, etc., the primary disease should be treated actively. At the same time, corresponding treatment should be carried out according to the treatment principles of type II RTA.

　　II. Prognosis

　　Mixed type renal tubular acidosis and type III renal tubular acidosis, if diagnosed and treated early and there is no renal calcification, the prognosis is generally good. Timely supplementation of alkali can delay the occurrence of renal calcification and kidney stones; some patients can spontaneously relieve; some patients with renal calcification, especially those with concurrent urinary tract infection, can develop into chronic renal failure and die.