Calcium phosphate is a common component in stones, and stones with higher calcium phosphate levels are usually at greater risk of recurrence. The incidence of pure calcium phosphate stones is not high, and the cause is mostly renal tubular acidosis. Renal tubular acidosis is a metabolic acidosis caused by acidification dysfunction of the renal tubules. There are four types of renal tubular acidosis. Of these, only distal (type I) renal tubular acidosis and proximal (type II) renal tubular acidosis cause urinary tract stones. The mechanism of stone formation is due to the weakening of renal acidification, which increases the urinary pH value, and calcium phosphate is more prone to precipitation and precipitation of crystals in an alkaline environment.
(1) Distal (type I) renal tubular acidosis: primary patients mostly have congenital defects of renal tubule function, which is inherited in an autosomal dominant manner; Secondary disease occurs in many disorders, most often secondary to pyelonephritis and sponge kidney. The pathogenesis may be due to tubular hydrogen pump failure, inability to secrete hydrogen, and inability to establish and maintain a large hydrogen ion gradient between luminal and peritubular fluids. Due to the dysfunction of urine acidification, the urine pH tends to be alkaline. At the same time, systemic metabolic acidosis strengthens the transfusion of citric acid in mitochondria, resulting in a decrease in the content of citrate in the urine, which is also one of the important causes of stone formation. It can occur at any age, often with a positive family history; Women account for about 80%; About 70% of patients are complicated with nephrolithiasis, and the clinical features are: hypokalemia, hyperchloremia, metabolic acidosis, normal anion gap, urine pH value persistently higher than 6, typical x-ray signs are multiple calculias in the calyxes of the kidney, sometimes renal papilla calcification, and even renal medullary stones. Occasionally, renal cortical stones and renal calcifications are present.
A small number of patients do not have systemic acidosis, but only show that the renal tubules cannot produce acidic urine, which is called incomplete renal tubular acidosis, which is characterized by normal blood pH and HCO-3 concentrations, urine pH > 5.5, and titratable acid.
(2) Proximal (type II) renal tubular acidosis: this disease is caused by excessive loss of HCO-3 due to dysfunction of renal tubular reabsorption of HCO-3. The pathogenesis has not been fully elucidated, but it may be related to the low activity of proximal tubular carbonic anhydride, which affects the formation of carbonic acid and the exchange of H+ in the renal tubules. In addition to hyperchloremic metabolic acidosis and hypokalemia, the most important feature of this disease is that HCO-3 in the urine is excreted in large quantities due to reabsorption dysfunction, and normal people generally do not have HCO-3 in their urine, while patients with proximal renal tubular acidosis can excrete HCO-3 often up to more than 15% of the content in the filtrate. Because the distal tubular function is normal, the urine pH can still be reduced to less than 5.5, so it is less likely to cause kidney stones and renal calcification. A few cases may also be incomplete, i.e., only urinary manifestations without systemic acidosis.
Uric acid stones account for about 5% of the total number of stones, and the formation of uric acid stones depends on three factors: (1) the amount of uric acid excreted; (2) Urine pH value; (3) Urine output. Unlike calcium-containing stones, no inhibitors of uric acid crystallization have been found so far.
Hyperuricuria: Excessive uric acid excretion in the urine is a major factor in the formation of acid stones. Uric acid, also known as 2.6.8-trioxoprine, is the end product of purine oxidative catabolism, which is mainly excreted by the kidneys. Clinically, the amount of uric acid excreted in the urine > 600mg/day is hyperuricuria. There are two major sources of uric acid in the human body: (1) exogenous uric acid comes from purines in food, after adults ingest purine 2mg/kg/day, about 200-300mg/day of uric acid is excreted in the urine, and eating purine-rich meat and fish, especially animal offal, is an important reason for the fluctuation of uric acid levels in the body; (2) Endogenous uric acid comes from the resynthesis of purines in the body and the nucleic acid degradation of tissue cells, about 300mg per day. The most common cause of excessive endogenous uric acid production is gout, which occurs in about 11% of cases with uric acid stones, followed by glucose-6-phosphatase deficiency, which presents with gout symptoms and uric acid stones at an early age. The increase in uric acid excretion due to increased endogenous nucleic acid breakdown is seen in lymphoproliferative diseases, such as lymphoma and leukemia, where there is a large increase in purines in the body due to the vigorous metabolism of nucleic acids in the body, resulting in hyperuricuria. Uric acid stones can be the first manifestation of these diseases. In addition, after chemotherapy and radiotherapy, a large amount of purines can also be produced due to tissue necrosis and decomposition, resulting in hyperuricuria.
LOW URIC PH: LOW URIC PH IS ALSO AN IMPORTANT FACTOR IN THE FORMATION OF URIC ACID STONES. The solubility of uric acid is pH dependent, and the solubility of uric acid is about 500mg/L when the urine pH value is 6.0. At a urine pH of 5.0, it drops to 100mg/L. When the urine pH value is greater than 6.5, uric acid mainly exists in the form of ionic urate, and generally does not form stones; on the contrary, when the urine pH value is lower than 5.5, the uric acid is all in a non-dissociative state, and if it reaches a supersaturated state, it will induce stone formation.
Urine PH value is an important basis for diagnosing uric acid stones for a long time below 5.5, and the normal urine PH value fluctuates repeatedly between 5 and 7 in a day, so it generally does not form stones, but the first morning urine PH value of 90% of patients with uric acid stones < 5.7, with an average of 5.5. This chronic persistent acidification of urine may also be a risk factor for uric acid stones in patients with gout, and the mechanism of persistent urinary acidification may be related to the decline of renal ammonia secretion. In addition, a variety of gastrointestinal diseases can also cause uric acid stones, among which chronic enteritis and intestinal resection are the most common, due to the large loss of bicarbonate, it can also cause a decrease in urine pH value, thereby inducing uric acid stone formation, but uric acid secretion is normal.
Low urine output: Uric acid stones are the most affected of all stones by temperature and water intake. Long-term exposure to the scorching sun and high temperatures or living in a dry environment, as well as those with high physical labor intensity, often lose a large amount of body fluid, and even dehydration, which reduces urine output and concentrates urine, resulting in supersaturation of uric acid in the urine. In addition, in some patients with inflammatory bowel diseases, in addition to excessive acidification of urine due to bicarbonate loss, excessive uric acid concentration in the urine caused by chronic dehydration is also an important cause of uric acid stone formation.
It should be noted here that uric acid stones differ from the previously described hyperuricurial uric calcium oxalate stones (HUCNs) in terms of concept and mechanism of stone formation. Although both are formed in the same state of hyperuricuria, the difference is that the former is generally formed after the formation of stones after the uric acid is supersaturated and crystallized when the urine PH is below 5.5, while the latter is when the urine pH value is greater than 5.5, the uric acid dissociates in the sodium-containing urine to form sodium urate, and then the sodium urate is nucleated through heterogeneous nucleation and combined with the crystal inhibitor in the urine, thereby inducing the formation of calcium oxalate stones.