Kidney stones: Pathology review

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Case study0:00–0:55

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.

Pathology0:55–2:04

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.

Calcium stones2:04–5:40

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.

Struvite stones5:40–6:47

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. However, you can see how the stone is occupying the renal calculi.
Treatment relies on killing off the bacteria with antibiotics and surgical treatment in order to remove the stone. Next, there are uric acid stones.

Uric acid stones6:47–7:47

At a physiologic urine pH which is about 5.5 to 7, meaning it’s acidic, uric acid loses a proton and becomes a urate ion, which then binds sodium, forming monosodium urate which crystallizes and ultimately forms uric acid stones.
Such stones are red-brown in color and rhomboid or rosettes in shape, and appear radiolucent on X-ray, and are minimally visible on CT-scan.
Risk factors for developing uric acid stones include acidic urine pH as well as dehydration. One important risk factor is hyperuricemia, which can happen in conditions like gout.
Other risk factors include conditions with a high cell turnover, such as leukemia. That’s because the tissue breakdown releases a lot of uric acid.
Treatment includes alkalinization of urine, as well as medications like allopurinol, which helps decrease uric acid levels.
Finally, a tiny minority of stones are cystine stones, composed of the amino acid cysteine which sometimes leaks into the urine to crystalize and form a yellow or light pink colored stone that’s hexagonal.

Cystine stones7:47–8:58

Cystine stones crystalize even more if the urine pH is acidic. For your tests, you can remember this using the following memory trick!
SIXtine-stones have SIX sides. On X-ray, it’s faintly radiolucent and on a CT-scan, it’s moderately radiopaque.
The main risk factor for cystine stones is cystinuria, an autosomal-recessive hereditary condition that manifests in childhood.
The protein affected is the amino-acid transporter in the proximal convoluted tubule which decrease reabsorption of ornithine, lysine, arginine, and most importantly, cystine.
The sodium cyanide nitroprusside test can detect cystine in the urine and is used to diagnose this disorder. Treatment involves a low-sodium diet, alkalinization of urine.
If this doesn’t work, chelating agents are administered. For your tests, it’s important to remember that all types of kidney stones generally present with the same symptoms, such as unilateral flank tenderness and pain, meaning between the ribs and the hip.

Symptoms8:58–9:40

Now, the pain is colicky and can radiate to the groin. This type of pain is called a renal colic, which is when there’s acute pain that’s so intense that it requires IV pain medication.The pain is caused by the dilation, stretching, and spasm caused by obstruction of the ureter, and is typically worse at the ureteropelvic junction and down the ureter, and subsides once the stone gets to the bladder.
There can also be hematuria that can either be gross or can be detected using urinalysis. Okay, now, sometimes, kidney stones can completely obstruct the ureter and this way the urine builds up behind the obstruction and they kidneys and ureters swell up.

Hydronephrosis9:40–10:28

The distention or dilation in the renal pelvis and calyces is called hydronephrosis. But remember!
Other disorder like benign prostatic hypertrophy, congenital obstructions of the ureter, cervical cancer, vesicoureteral reflux and retroperitoneal fibrosis can all lead to hydronephrosis.
Now, all that distention compresses the kidney, which can further lead to atrophy of the renal cortex and medulla. When the obstruction is bilateral or if the person only has one kidney, there’s no urine flow and this means that the kidneys aren’t functioning at all and creatinine levels go up.
Okay, let’s review! There are 4 main types of kidney stones.

Review10:28–12:22

The most common is a calcium stone which is usually a calcium oxalate stone, but can also be a calcium-phosphate stone. Risk factors for calcium oxalate stones include idiopathic calciuria, hypercalcemia, hypocitraturia, fat malabsorption, ingestion of ethylene glycol or antifreeze and vitamin C abuse, while risk factors for calcium phosphate stones include highly alkaline urine.
Treatment of calcium stones includes thiazides, low-sodium diet and citrate. Another type is a struvite stone which is also called an infection stone, because it forms in individuals that have a urinary tract infection with a urease-positive bug, like Proteus mirabilis.
Treatment relies on eradicating the infection and surgically removing the stone. Another type of stone is a uric acid stone that usually appears in individuals with hyperuricemia and treatment relies on alkalinization of urine and allopurinol.
Cystine stones are super rare and the main risk factor is a hereditary condition that causes cystinuria. Treatment involves a low-sodium diet, alkalinization of urine and if this doesn’t work, then chelating agents are administered.
Symptoms of a kidney stone include colicky flank pain that can radiate in the groin and hematuria. A X-ray and a CT-scan can be done to identify the location of the stone and sometimes, even the type!
When the kidney stones obstruct the ureter, this can lead to swelling in the renal pelvis and calyces called hydronephrosis.
Hydronephrosis has other causes, like benign prostatic hypertrophy, congenital obstructions of the ureter, cervical cancer, injury to the ureter, vesicoureteral reflux and retroperitoneal fibrosis.
Now, back to our cases. Conrad came in with colicky flank pain, nausea, vomiting caused by the pain, probably.

Summary12:22–13:00

Urinalysis showed that Conrad has hypercalciuria and hematuria with normal calcium levels in the blood. The CT-scan showed a radiopaque stone in the ureter and based on the test results, this is most likely a calcium stone!
Sam came in with flank pain and dysuria and urinalysis showed positive hematuria and nitrites, as well as positive leukocyte esterase.
The positive leukocyte esterase and nitrites suggest a urinary tract infection and the CT-scan showed a struvite stone in the kidneys!
Kidney stones: Pathology Review: Video and Anatomy | Osmosis