It is truly a personal embarrassment when your own biological plumbing system runs amok.

I had found myself in an unfamiliar situation in which, mere minutes after I had left a bathroom, I would have to go again with the same urgency and acute desperation as previously. It took me months to realize that perhaps this wasn’t quite normal or healthy for a woman of my age and health. No red flags had gone off in my head until the sensations to go grew to disproportionate levels. Don’t worry, I will spare you of all the remaining TMI symptoms and diagnosis protocols. In short, a sonogram ruled out infection and gave me the simple explanation I was looking for – my body had quietly formed at least three small kidney stones.

The point of my anecdotal bantering is that the formation of kidney stones is largely a chemical phenomena, and can be better understood and possibly prevented by understanding the mechanism of how stones form.

There are many different types of stones with varying chemical compositions, although the most common are composed of either calcium oxalate, uric acid, magnesium ammonium phosphate (AKA struvite stones), calcium phosphate, or cystine. Stone formation involves the behavior of ions in solution (i.e. your urine) under a system of chemical equilibrium.

Blogger Nivetha Uthayakumar explains calcium oxalate stone formation as a reversible reaction between free calcium cations and kidney by-product oxalic acid (the dissociation into oxalate anions can be described by the reaction C 2 H 2 O 4 (aq) ↔ C 2 O 4 2- (aq) + 2H+ (aq)) and solid calcium oxalate. Furthermore, he states that “the oxalic acid in the body reacts with the calcium ions found in the kidney to form calcium oxalate solids (or crystals) in the kidney. Depending on the various factors that affect equilibrium and Le Chatelier’s Principle, the system will either shift towards the left, right or remain the same to obtain equilibrium”.

This means that as more of ions present in the product side of the above equation are introduced in the urine, calcium oxalate precipitation will likely occur. I suspect that in my case the combination of an oxalate-rich, low calcium diet, along with inadequate hydration, promoted stone formation in my kidneys.

Unsurprisingly, the process of chemical equilibrium does not provide the physical explanation of how and why kidney stones form. Masao Tsujihata details that stone formation primarily begins with urinary supersaturation and resultant crystal formation. For clarification, a solution is said to be supersaturated when a solute is dissolved in a solvent beyond what is capable under normal circumstances. Next, stone crystal formation can occur via nucleation, whereby calcium oxalate particles aggregate on uneven surfaces of the kidney. Tsujihata cites evidence that cell degradation due to renal tubular cell injury can actually promote the formation of stones due to the increased number of nucleation sites on the kidney. After nucleation, the crystals grow and aggregate with other crystals to form sizable stones that can interact with neighboring renal tubular epithelial cells before breaking off and travelling down the urinary tract, which can be an extremely painful process.

The principles of chemical equilibrium can be applied to the other types of stones that are likely to form due to various diseases and health conditions that cause urine pH to be abnormally low (acidic) or high (basic). For instance, uric acid kidney stones form when urine is unusually acidic. In this case, the acid-base equilibrium lies between uric acid and urate ion, the anion or salt form of this compound.

The Henderson Hasselbach equation for uric acid (with pKa = 5.7) in urine is:

pH = pKa + Log [Urate]/[Uric Acid]

By working out the equation at varying pHs, you’ll understand that as the pH of urine decreases, the solubility of uric acid decreases as the solubility of urate ion increases. Interestingly enough, just as humans form many calcium oxalate crystals every day that do not transform into kidney stones per se (they pass through the urine without nucleation and large crystal growth), it is very common for non-stone formers to have uric acid crystal formation without its development into stones. Ngo and Assimos explain this phenomena as a result of intermittent urine alkalinity that provides just enough basicity to allow for uric acid solubility. Furthermore, they explain that “the primary defect for this absence of alkaline tides can theoretically occur at several places: defective gastric acid secretion, decreased glomerular filtration rate leading to decreased filtered load of bicarbonate, and increased renal tubular reabsorption of bicarbonate.” Although the data still fails to link these “alkaline tides” with lack of stone formation in patients with occasionally low pH, studies have found that uric acid stone formers tend to have persistently low urine pH.

There are many biological explanations given for high urine acidity, although Ngo and Assimos cite that stone-formers with low urinary pH release less of their body’s uric acid by-product load as ammonium (a process that occurs in the gut), and thus more of it remains in the urine.

I won’t go into too much detail about the other stone types, but I’ll briefly outline the underlying acid-base chemistry for each case.

Struvite stones, with formula NH 4 MgPO 4 ·6H 2 O (ammonium magnesium phosphate hexahydrate), are typically associated with bacterial infections. In this case, urea breaks down into ammonium and carbon dioxide by the enzyme urease (not stoichiometrically balanced):

In aqueous solution, ammonium forms NH4+ and OH- ions, increasing urine’s pH as well as carbonate and phosphate anion concentration. At high enough pH, ammonia and phosphate ions combine with the magnesium adsorbed on the surface of the infectious bacteria to produce struvite crystals, which grow to stones in the typical manner. Calcium phosphate stones form from this pathway when the phosphate ions combine with calcium from urine.

Cystine stone formation involves a somewhat different pathway than those described for the above types.

Cystine precipitation due to the genetic disorder cystinuria simply results in an excess of the molecule in the urine. Since cystine is the least soluble amino acid in urine, an abnormal excess would certainly provide the right conditions for stone formation.

Looking at all the structures together, it’s easy to grasp how acid-base and solution chemistry take part in kidney stone formation. Hopefully this bit of information will allow you to become a more informed patient!

Sources:

Blog: https://fmss12uchemd.wordpress.com/2013/05/06/chemical-equilibrium-the-development-of-kidney-stones-by-nivetha-uthayakumar/comment-page-1/

Paper: Tsujihata, M. (2008, February 15). Mechanism of calcium oxalate renal stone formation and renal tubular cell injury. International Journal of Urology. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18269444

Paper: Ngo, T., & Assimos, D. (2007). Uric acid nephrolithiasis: Recent progress and future directions. Reviews in Urology. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831527/

Website: http://faculty.une.edu/com/courses/bionut/distbio/obj-512/Chap5-urate%20solubility.html

Paper: Sun, X. et al. (2015, March 19). Formation mechanism of magnesium ammonium phosphate stones: A component analysis of urinary nanocrystallites. Journal of Nanomaterials. Retrieved from http://www.hindawi.com/journals/jnm/2015/498932/

Website: http://www.medicinenet.com/script/main/art.asp?articlekey=8529

Chemical structures created by ChemDraw.