Kidney stones: Pathology review

In the Emergency Department, two people with similar symptoms came in.

One of them is 35 year old Conrad who has a terrible left flank pain, along with nausea and vomiting and the other one is 40 year old Sam who has left flank pain, but also has dysuria.

An electrolyte panel and urinalysis was done in both individuals.

Results showed that Conrad had normal levels of calcium in the blood, but urinalysis showed hypercalciuria and hematuria.

Sam’s urinalysis showed positive leukocyte esterase, as well as positive nitrites and hematuria. Abdominal CT showed radiopaque masses in their ureters.

Now, the suspicion is that both individuals have kidney stones, but there are actually several types of kidney stones and we need to know what we’re dealing with in order to give the right treatment.

Okay, let’s first talk about how kidney stones form.

Urine’s a combination of water, which acts as a solvent, and all sorts of particles, or solutes.

In general, when certain solutes become too concentrated in the solvent, they become supersaturated.

Urinary supersaturation of certain solutes results in precipitation out of the solution and formation of crystals.

Those crystals then act as a nidus, or place where more solutes can deposit and over time it builds up a crystalline structure.

This can happen if there’s an increase in the solute, or a decrease in the solvent, as would be the case with dehydration.

This means that dehydration leads to a low urine volume which can further put a person at risk for kidney stones.

Okay, let’s now talk about the different types of stones.

There are four main types of stones.

Calcium stones are present in about 80 percent of the cases, while struvite stones are present in about 15 percent of the cases and uric acid stones are present in about 5 percent of the cases.

Finally, a super rare type of stone is a cysteine stone.

Let’s start with calcium stones.

With calcium stones, in most cases, the inorganic precipitate is calcium oxalate, formed by a positively charged calcium ion binding to a negatively charged oxalate ion, which results in a black or dark brown colored stone that’s shaped like an envelope or a dumbbell.

Calcium oxalate stones appear radiopaque on X-ray, as well as on a CT-scan.

Now, there are some risk factors for developing calcium stones, such as idiopathic hypercalciuria or hypercalcemia.

Another very important risk factor is hypocitraturia, which means that less citrate is eliminated in the urine.

This is because normally, citrate prevents stone formation by inhibiting crystal growth and aggregation.

Other risk factors include fat malabsorption, which can happen with Crohn’s disease or in individuals that have had a gastric bypass operation.

This happens because since fat won’t be absorbed in the intestine, it will bind to calcium and this leaves a lot of oxalate free to be absorbed in the intestine, which raises oxalate levels in the blood and can further promote calcium oxalate stone formation.

Another risk factor is the ingestion of ethylene glycol or antifreeze, because ethylene glycol forms oxalate once ingested.

Finally, there’s vitamin C abuse, because one product of vitamin C metabolism is oxalate.

Now, treatment of calcium-oxalate stones involves giving thiazide diuretics.

Thiazides inhibit the sodium-chloride transporter in the distal convoluted tubule, meaning that more sodium and chloride get in the urine.

Okay, the distal convoluted tubule also has a calcium channel which allows calcium from the lumen to diffuse into the cell.

Once in the cell, calcium is transported out into the interstitium through a sodium-calcium exchanger, that pumps a sodium in, and a calcium out.

Now, since thiazides decrease sodium reabsorption, there’s less sodium in the cell, so the sodium-calcium exchanger works overtime to pump more sodium in, and more calcium out.

The decrease in intracellular calcium, in turn, leads to more calcium reabsorption from the urine. Another treatment is giving potassium citrate which binds to the calcium in urine, preventing reabsorption.

Finally, another treatment involves a low-sodium diet.

That’s because when a person has a high sodium diet, more water is retained.

This means that the extracellular volume expands.

Since there’s so much water and sodium, the renin-angiotensin-aldosterone system has nothing to respond to, so its activity is dialed down.

This means that not that much sodium will be reabsorbed in the proximal convoluted tubule.

Now, calcium and sodium reabsorption are tied together in the proximal convoluted tubule, so when there’s less sodium reabsorption, there’s also less calcium reabsorption and there will be hypercalciuria.

Sometimes, instead of oxalate, the calcium bind to negatively charged phosphate groups to form calcium phosphate stones.

These are dirty white in color and shaped like a wedge prism which appears radiopaque on a X-ray.

A risk factor is highly alkaline urine which could be caused by renal tubular acidosis where there’s a decreased secretion of hydrogen or increased secretion of bicarbonate into the urine. Treatment includes a low-sodium diet, as well as thiazide diuretics.

Another type are struvite stones, sometimes called infection stones, which are a composite mix of magnesium, ammonium, and phosphate.

Since they are infections stones, this means that the individual can present with signs of a urinary tract infection, like dysuria.

For your tests, remember that these form when there’s an overabundance of urease-positive bugs like Proteus mirabilis, Staphylococcus saprophyticus, and Klebsiella species.

They use the enzyme urease to split urea into ammonia and carbon dioxide.

The ammonia makes the urine more alkaline and favors precipitation of magnesium, ammonium, and phosphate into jagged crystals called “staghorn” because they often branch into the several of the renal calyces and look like the horns of a staghorn deer.

On an X-ray or on a CT-scan, such stones are radiopaque,, but are less dense than calcium stones.