15. Pathomechanism and clinicopathological forms of stone formation
Cholelithiasis
The presence of gallstones in the gallbladder is called cholelithiasis. It affects 20% of adults in western countries. We distinguish two main types of gallstones: cholesterol stones, which are made up of crystalline cholesterol and accounts for 80% of stones found in the west, and pigment stones, made up of bilirubin calcium salts.
The presence of stones in the common bile duct is called choledocholithiasis.
Cholesterol stones are always formed in the bladder. They consist of 50-100% cholesterol and are greyish-yellowish. These stones are usually bigger and occur in small numbers. They’re invisible on x-ray.
Pigment stones may form anywhere in the biliary tree. They’re comprised of calcium salts of unconjugated bilirubin, other calcium salts and mucin. Two types exist: Black stones and brown stones. The black stones are often found in sterile gallbladder bile, while brown stones are often found in infected bile ducts. Black stones tend to be small, fragile and occur in large numbers while brown stones tend to be larger, soft and greasy and occur in small numbers. Black stones can be seen on x-ray.
The risk factors for gallstones are the 6 F’s, plus a few more:
- Fat
- Female
- Fertile
- Forty
- Fair-skinned
- Family history
- Haemolytic anaemia
- Contraceptives
- Pregnancy
- Rapid weight loss
Pathogenesis and clinical features
The only pathway the body has to get rid of cholesterol is be excreting it into bile. Cholesterol is not soluble in water, but it is soluble in bile salts. However, if the concentration of cholesterol in the bile exceeds the solubilizing capacity of the bile will the bile become supersaturated by cholesterol. This causes cholesterol to crystallize.
Stone formation begins similarly to calcification: it begins with nucleation (formation of a core), which will then propagate to become larger.
This process is enhanced by hypomotility of the gallbladder. When the gallbladder isn’t actively used, bile remains stale, which increases the probability for nucleation to start. An increased secretion of mucus also increases the risk for stone formation, because the mucus traps the stones, so they can propagate.
The clinical consequences of gallstones can be:
- Severe right upper quadrant pain
- Acute or chronic cholecystitis
- Chronic can lead to fibrosis
- Can occur with empyema (pus accumulation)
- Gallbladder cancer
- Fistula formation
- Perforation
- If a stone is stuck in common bile duct
- Post-hepatic/obstructive jaundice
- Ascending cholangitis
- The ascending inflammation of the bile duct due to bacteria ascending from the intestine while the bile duct is obstructed
- If a stone is stuck in the Vater’s papilla
- Acute pancreatitis
- Chronic pancreatitis
80% of patients with stones are asymptomatic, and the stones are only found during autopsy. The fraction that do experience symptoms experience severe pain in the right upper quadrant. The pain is caused by gallbladder or biliary tree obstruction or even cholecystitis.
The smallest stones are actually the most dangerous and vice versa. The big stones can’t get into the biliary ducts to obstruct them, while the small stones can.
Gallstones can be removed by a procedure called Endoscopic Retrograde CholangioPancreatography (ERCP). It involves an endoscope with an x-ray on it that can navigate into the biliary tree and destroy the stones.
Urolithiasis
The calculus formation in any level in the urinary collecting system is called urolithiasis. Stones arise most commonly in the kidney. Symptomatic urolithiasis is more common in men than in women.
Like for cholelithiasis will stones be formed only when the urine concentration of a certain salt is higher than the salts solubility in urine, making a supersaturated solution. Certain factors like urine pH and bacterial infections may increase the risk for urolithiasis.
Four different types of kidney stone exist:
Calcium stones are composed of calcium oxalate with or without calcium phosphate. These stones represent the majority of kidney stones. 50% of patients who develop calcium stones don’t have hypercalcaemia. Instead, they either absorb too much calcium from the gut (absorptive hypercalciuria) or have a renal defect in calcium absorption (renal hypercalciuria).
Struvite stones are composed of magnesium ammonium phosphate. This type occurs in persons with alkaline pH, often because of a urinary tract infection.
Uric acid stones are seen in disorders where the uric acid level of the blood increases, or in patients with acidic urine. In gout the uric acid level is high. Certain diseases increase the cell turnover rate, like leukaemias, which also increases the uric acid level.
Cystine stones are associated with a genetic defect in the renal transport of the amino acid cysteine. Acidic urine also increases the risk for cystine stones.
Pathogenesis and clinical features
Stones usually occur unilaterally, in the renal pelvis, calyces or the bladder. Many small stones are usually found at the same time. They tend to be just a few millimetres in diameter and can be smooth or jagged.
Sometimes can stones grow so large that they take on the shape of the renal pelvis, like a cast. These stones are called staghorn calculi.
Stones may present with severe intense pain with sudden onset that radiates toward the groin. This pain is called renal or ureteral colic. Often there is also haematuria.
The stones may also obstruct urine flow or cause ulceration and bleeding of the location they’re in. They also increase the risk of bacterial infection.
Kidney stones can be crushed non-invasively by ultrasound waves, a technique called ESWL. They can also be crushed and removed by ureteroscopy or percutaneous lithotomy.