Distal renal tubular acidosis
Introduction
Introduction to distal renal tubular acidosis Distalrenal tubular acidosis, also known as classic RTA (DRTA, ITypeRTA), is a disease caused by a decrease in urinary NH4 and titratable acid excretion due to distal tubules. Its clinical features are high chloride metabolic acidosis, hypokalemia, hypocalcemia, hyponatremia, urinary acidification (urinary pH>6), etc. [RTA is a comprehensive Signs are more common in clinical practice. basic knowledge The proportion of illness: 0.005% Susceptible people: no special people Mode of infection: non-infectious Complications: vitamin C deficiency, kidney stones, uremia, neurological deafness
Cause
Causes of distal renal tubular acidosis
(1) Causes of the disease
The cause of distal RTA can be divided into primary and secondary.
Primary people are related to heredity and are autosomal dominant. They have a family history, but they are mostly sporadic. Secondary diseases can be caused by many diseases. The most common root diseases are chronic renal tubules and interstitial nephritis. Among them, chronic pyelonephritis is more common, in addition, other congenital hereditary kidney diseases such as sponge kidney, Fabry disease, idiopathic hypercalciuria, etc. can be caused in China, secondary to Sjogren's syndrome, systemic The incidence of distal RTA in autoimmune diseases such as lupus erythematosus has a high incidence, and DRTA caused by gossypol poisoning in cotton producing areas due to consumption of raw cottonseed oil has also been reported.
(two) pathogenesis
1. Distal renal tubular acidification of urine The distal renal tubule is different from the proximal renal tubule in that it has different effects on HCO3-resorption, and only absorbs the remaining HCO3- to form 1/3 of the acid in the acidification process. Its main form is the secretion of H, which increases the formation of NH4, and finally excretes the acid produced in the body.
The function and morphology of distal renal tubular cells can be divided into two categories:
(1) Main cells: related to the secretion of K and reabsorption of Na, do not directly affect the acidification process.
(2) cells (intercalated cells): related to secretion of H, directly involved in the acidification process, the cell secretion H depends on H-ATPase (ie hydrogen pump) and Na is not directly related, there are a large number of cells in the II Type CA combines OH- produced by secretion of H with CO2 to form HCO3-, and reabsorbs HCO3- through the peri-C1-, HCO3- exchange system.
Most of the distal renal tubules secrete hydrogen through the formation of NH4 with ammonia, which is mainly formed by deamination of glutamate in the proximal renal tubules, and then combined with H to form NH4 and secreted into the small lumen. Active reabsorption of NH4, the distal renal tubules are mainly passively dispersed by H pumping into the active secretion H and the transmembrane concentration difference of NH3 in the lumen, so that the NH3 concentration is increased, NH3 and H combine to form NH4, and then strong in the lumen. The Na exchanged by the acid salt (such as NaCl, Na2SO4, etc.) is combined with NH4Cl, and (NH4)2SO4 is discharged from the urine; Na enters the cell and is recovered to the blood, thereby achieving secretion of H, acidification of urine and formation of carbonic acid. Sodium hydrogen reduces the pH of the urine to 4.5-5.5, which is 2 to 3 pH units lower than the blood pH.
The cortical collecting tube is the part where Na exchanges with H and K. The H pump secretion rate is affected by the potential in the lumen. Under the action of aldosterone, Na is reabsorbed in the small tube fluid, and a negative potential is formed in the cavity to promote H, K along The potential difference is secreted into the lumen, and the medullary collecting tube is not reabsorbed by Na. The secretion of H is a positive potential in the cavity against the electrical gradient, and the net HCO3-resorption rate is 10 times larger than that of the cortical collecting tube. Normally, the distal end The tubular epithelial cells are tightly connected, and the H secreted into the lumen is not easy to leak back, thus maintaining a steep H concentration gradient between the renal tubule and the blood, and lowering the urine pH to below 6.0.
2. Distal renal tubular secretion H dysfunction due to various internal factors, energy, metabolism and other factors, the distal nephron medullary collecting duct interstitial cells and a few cortical part of the main cell dysfunction, leading to kidney A small tube of H dysfunction, Joo et al found through a histochemical examination of 1 case of Sjogren's syndrome and 1 case of idiopathic distal renal tubular acidosis, 2 cases of interstitial cell anti-H of distal renal tubules Immunohistochemical staining of ATPase was significantly lighter than normal control, which proved to be a defect of H ATPase pump rather than selective loss of interstitial cells. It is believed that the pathogenesis of distal renal tubular acidosis is as follows:
(1) H ATPase pump failure: when certain diseases destroy the H pump of the distal nephron (such as renal interstitial disease) or certain toxins inhibit the function of the H pump, and the genetic defect of the H pump (hereditary d-RTA) can cause the H pump function to fail and cause H secretion disorder. The tubular epithelium can not secrete H, and the urine pH can not be properly reduced. This is the most common cause of d-RTA. This type is secretory defect. ).
(2) Gradient defects: Some factors (such as amphotericin B) can cause abnormal permeability of the "tight junction" of distal nephron epithelial cells, and increase H leakage (cell membrane defects increase H permeability, H Reverse flow into the small tube,) the steep H concentration gradient cannot be maintained in the lumen and the net acid excretion is reduced. This type is also called the gradient defect.
(3) H pump secretion rate decreased: proton pump secretion H rate decreased, more common in lithium-treated patients, H secretion rate decreased, may be the early performance of DRTA, this type is rate-dependent defect (rate-dependent defect).
Prevention
Prevention of distal renal tubular acidosis
There is no effective preventive measure for type I RTA caused by primary hereditary causes, and the prevention of secondary diseases should start from the treatment of basic diseases, control the development of renal tubular acidosis, and actively treat patients with existing diseases. To prevent the disease from progressing and to strive for a good prognosis.
Complication
Distal renal tubular acidosis complications Complications, vitamin C deficiency, kidney stones, uremia, neurological deafness
Nutritional disorders, vitamin C deficiency or osteomalacia, some kidney stones or kidney calcification, late development into uremia, a few have neurological deafness.
Symptom
Symptoms of distal renal tubular acidosis Common symptoms Kidney area dull pain, fatigue, urinary nausea and vomiting constipation, dehydration, kidney stones, renal calcification
DRTA is the most common clinical type of renal tubular acidosis, which can occur at any age, more common in 20 to 40 years old, especially in women, the disease can be asymptomatic, typical:
1. Perchloric acidosis due to H disorder, urine titratable acid and NH4 emission decreased, urine can not be acidified, so the urine pH is often >6, in addition, due to the proximal renal tubular function is still good, can reabsorb HCO3-, urine HCO3- There is not a lot of displacement. Due to the continuous loss of Na, the extracellular fluid volume is contracted, the aldosterone secretion is increased, the absorption of chlorine is increased, and hyperchloremia is formed. Another person thinks that hyperchloremia and some unexplained cause make the nephron "Real chloride shunt" caused by increased chloride permeability.
2. Electrolyte Disorders Due to the decrease in H-K pump function of the H pump and cortical collecting tube of the distal nephron, the kidney cannot maintain potassium and concentrate urine, so polyuria, hypokalemia and acidosis, low potassium occur. It also causes polyuria, polyuria and aggravation of hypokalemia. If additional load of miscellaneous disease occurs, acidosis and hypokalemia may cause death; acidosis inhibits renal tubular reabsorption of Ca2 and vitamin D activity. Causes hypercalciuria and hypocalcemia, forms "three low and one high" electrolyte disorder with hypokalemia, hyponatremia, hypocalcemia and high blood chlorine. In addition, hypokalemia can also cause muscle weakness and muscle paralysis. Due to the reduced exchange of H-Na in the tubule fluid, a large amount of sodium can be lost in the urine, and the patient may have neurological deafness.
3. Osteopathic hyperparathyroidism caused by hypocalcemia, bone pain, bone decalcification such as fractures further develop into rickets (adults) or vitamin C deficiency (children).
4. Renal calcification and kidney stones due to a large number of calcium, urinary citrate decreased and urine is alkaline, it is easy to make calcium salt deposition to form renal calcification, kidney stones, further renal colic, hematuria and urinary tract infection.
5. In the early stage of renal dysfunction, polyuria may occur due to impaired renal tubular concentrating function, and uremia may occur in advanced glomerular involvement. According to the correlation of clinical symptoms, it is summarized.
The disease is clinically divided into the following 4 types:
1 myopathy type: muscle weakness, even respiratory muscle paralysis, difficulty breathing, decreased blood potassium, increased urinary potassium, electrocardiogram showing hypokalemia, may be associated with atrioventricular block, arrhythmia, etc., due to low potassium paralysis In the emergency department, you should be vigilant;
2 bone type: mainly for bone pain and pathological fractures, patients can reduce activity due to bone pain, and even bedridden, X-ray examination shows osteoporosis, multiple, symmetry, pseudo-fracture, etc., showing teeth Loose and easy to fall off, the child does not have teeth;
3 urinary calculi type: urinary sand, urinary stones, hematuria, renal colic, urinary tract obstruction and repeated urinary tract infections;
4 incomplete type: a small number of patients have no systemic acidosis, only the renal tubules do not produce acidic urine, called incomplete distal renal tubular acidosis, ammonium chloride load test urine pH is not reduced, incomplete distal Renal tubular acidosis can progress to complete form.
Vitamin D deficiency, rickets, calcium phosphate stones or renal calcification, provide diagnostic clues, especially high blood chlorine metabolic acidosis, and urine pH can not be reduced to <6.0, has a characteristic diagnostic significance, If hyperchloremia and hypokalemia metabolic acidosis is found, and inappropriate high urine pH (>5.5) is found, distal renal tubular acidosis can be diagnosed. Some mild patients may have no systemic metabolic acidosis. The performance, but the function of renal tubular acidification of the urine is impeded, this is the so-called "incomplete type 1 RTA", so clinically unexplained hypokalemia, kidney stones or renal calcification, should think of "type 1 RTA" "Maybe, after correcting hypokalemia, it can be used as an ammonium chloride load test to aid diagnosis. After 2 days of discontinuation of the basic drug, oral ammonium chloride 1.9mmol (0.1g) / kg (body weight) per day, After 3 to 4 times of service, even for 3 days, after the test, there is metabolic acidosis, pH <7.34, CO2CP 20mmol / L (in the absence of respiratory factors, carbon dioxide binding capacity is reduced, can represent metabolic acid Poisoning), and the urine pH can not be reduced to 5.4, which suggests that the distal convoluted tubule acidified urine function Obstruction, help to confirm the diagnosis, such as acidemia is mild, it should be simplified ammonium chloride test; that is, ammonium chloride 1.9mmol (0.1g) / kg (body weight) 30 ~ 40min service, this amount will generally Serum HCO3- decreased by 4-6 mmol/L (normal 18-20 mmol/L), urine samples were collected 6-8 h after service, and the results were the same as above. Patients with bacterial urinary tract infection with urea-degrading enzyme could produce alkaline urine. , can make this test a false negative should pay attention to, there are severe high blood chlorine acidosis and urine has been significantly alkaline, it is not necessary to do this test.
Examine
Remote renal tubular acidosis test
1. Urine pH measurement Urine pH reflects the amount of H in the urine. In DRTA, although the blood pH is <7.35, the urine pH is still 6.0, and can also be as high as 6.5,7.0 or more. The urine pH must be measured by a pH meter. There are certain limitations, urine pH <5.5 does not indicate that the uric acid function must be intact, such as patients with NH3 barrier, because a small amount of H can not be combined with NH3 into NH 4, urine pH can still be <5.5, so the urine pH should be measured simultaneously Urine NH 4, judged by comprehensive analysis.
2. Determination of urine titratable acid and urine NH 4 Most of the H secreted by the distal tubules is combined with NH3 to form NH 4 and the other part is discharged as titratable acid. Therefore, the sum of urine titratable acid and NH 4 Represents the net acid excretion of the kidney. When the acidity in the body increases, the normal human urine pH can be <5.5, and the urinary titratable acid and NH 4 excretion rate can reach 25mol/min and 39mol/min, respectively, in distal renal tubular acidosis. Both of them are significantly reduced.
3. Determination of urinary electrolytes and urinary anion gap DRTA mostly had increased urinary sodium excretion and increased urinary calcium, urine Ca/Cr>0.21, 24h urinary calcium>4mg/(kg·d), urinary anion gap=Na +K -Cl- It can reflect the urine NH 4 level. When it is positive, it indicates the decrease of urinary NH 4 excretion, urine pH>6.0, HCO-excretion fraction <5%, urine NH4 <500mmol/d, 24h urine Na, K, Ca2, PO43- discharge increase.
4. Blood gas analysis and electrolyte determination The typical change of DRTA is normal metabolic acidosis with hyperchloritemia anion gap. Incomplete DRTA can be characterized by compensatory metabolic acidosis or normal, anion gap (anion gap, AG)=Na +K -(Cl-+HCO3-), normal 8~16mmol/L, the increase indicates the accumulation of acidic products such as inorganic acid radicals (such as nitrate, sulfate) and (or) organic acid ions in the body, RTA When Cl- compensates for the decrease of HCO3-, the AG is normal, and the decrease of blood potassium is also an important manifestation of DRTA, even the only manifestation of incomplete DRTA, blood sodium and blood calcium can be normal or decreased.
5. Detection of urinary carbon dioxide partial pressure After normal people give sodium bicarbonate or neutral phosphate, the amount of HCO3- or HPO2-4 reaching the distal tubule increases. The former combines with H to form H2CO3; the latter combines with H to form H2PO4-, and then H2CO3 is formed with HCO3-, and CO2 is formed to increase the partial pressure of urinary CO2. In the case of DRTA, the urinary CO2 does not rise due to hydrogen secretion disorder, and the difference between urinary CO2 partial pressure and blood CO2 partial pressure is <20 mmHg, and normal person>30 mmHg.
6.24h urinary acid DRTA is often reduced.
7. Blood tests mainly showed blood K, Ca2, Na, PO43-low, blood Cl- increased, plasma HCO3- decreased, and CO2 binding decreased.
1. Imaging examination can understand the bone disease and find kidney stones.
2. Ultrasound examination can understand whether the kidney has calcification and stones.
Diagnosis
Diagnosis and diagnosis of distal renal tubular acidosis
Distal renal tubular acidosis can sometimes be confused with uremia acidosis, but metabolic acidosis of uremia has azotemia and elevated blood phosphorus, and identification is not difficult.
Renal calcification caused by hereditary idiopathic hypercalciuria can cause distal renal tubular acidosis, and it needs to be differentiated from the primary one. The stone at this time can be calcium phosphate stone, but no low potassium. Hemorrhagic and metabolic acidosis, incomplete RTA, the most easily and idiopathic hypercalcemia can not be distinguished, at this time, can be used for ammonium chloride load test, secondary distal renal tubular disease caused by other diseases Acidosis has its own clinical characteristics.
DRTA should also be differentiated from glomerular acidosis, various vitamin D deficiency diseases, and familial periodic paralysis.
1. Glomerular acidosis has a history of kidney disease, obvious urinary abnormalities, often accompanied by anemia and hypertension, blood Cr-normal and increased serum creatinine, blood and urine pH consistency.
2. Familial periodic paralysis has a family history, more common in men, normal urine test, no acidosis, often full of meals before the onset, high sugar diet, strenuous exercise, trauma, infection and other incentives.
3. Familial hypophosphatemia anti-vitamin D rickets Symptoms and signs of rickets are prominent, but no acidosis and other dRTA manifestations.
