Depending on the chemical composition of the crystal, the stone-forming process may proceed more rapidly when the urine pH is unusually high or low.Supersaturation of the urine with respect to a calculogenic compound is pH-dependent. For example, at a pH of 7.0, the solubility of uric acid in urine is 158 mg/100 ml. Reducing the pH to 5.0 decreases the solubility of uric acid to less than 8 mg/100 ml. The formation of uric-acid stones requires a combination of hyperuricosuria (high urine uric-acid levels) and low urine pH; hyperuricosuria alone is not associated with uric-acid stone formation if the urine pH is alkaline. Supersaturation of the urine is a necessary, but not a sufficient, condition for the development of any urinary calculus. Supersaturation is likely the underlying cause of uric acid and cystine stones, but calcium-based stones (especially calcium oxalate stones) may have a more complex cause. Randalls plaque
While supersaturation of urine may lead to crystalluria, it does not necessarily promote the formation of a kidney stone because the particle may not reach the sufficient size needed for renal attachment. On the other hand, Randalls plaques, which were first identified by Alexander Randall in 1937, are calcium phosphate deposits that form in the papillary interstitium and are thought to be the nidus required for stone development. In addition to Randalls plugs, which form in the Duct of Bellini, these structures can generate reactive oxygen species that further enhance stone formation. Pathogenic bacteria
Some bacteria have roles in promoting stone formation.
Overall, neither growth hormone nor aromatase inhibitors are recommended for constitutional delay to increase growth.Girls can be started on estrogen with the same goals as their male counterparts.Overall, studies have shown no significant difference in final adult height between adolescents treated with sex steroids and those who were only observed with no treatment. Malnutrition or chronic disease
If the delay is due to systemic disease or malnutrition, the therapeutic intervention is likely to focus direction on those conditions. In patients with coeliac disease, an early diagnosis and the establishment of a gluten-free diet prevents long-term complications and allows restoration of normal maturation. Thyroid hormone therapy will be necessary in the case of hypothyroidism. Primary failure of the ovaries or testes (hypergonadotropic hypogonadism)
Whereas children with constitutional delay will have normal levels of sex hormones post-puberty, gonadotropin deficiency or hypogonadism may require lifelong sex steroid replacement.In girls with primary ovarian failure, estrogen should be started when puberty is supposed to start. Progestins are usually added after there is acceptable breast development, about 12 to 24 months after starting estrogen, as starting treatment with progestin too early can negatively affect breast growth. After acceptable breast growth, administering estrogen and progestin in a cyclical manner can help establish regular menses once puberty is started. The goal is to complete sexual maturation over 2 to 3 years. Once sexual maturation has been achieved, a trial period with no hormonal therapy can determine whether or not the child will require life-long treatment.