• BIO 381 Pathophysiology
  • Download
  • Translations
  • 12.1.3

    Obstructive Disorders and Kidney Stones

    Many conditions can lead to obstruction of urine flow. This obstruction may occur anywhere from the renal pelvis to the urethra. The obstruction may be due to externally applied pressures - as with a tumor or pregnancy, or inside urinary tract structures, as with renal calculi or strictures. Other causes include neurogenic bladder after spinal cord injury and benign prostatic hyperplasia (BPH) in males. Upper obstructions are those above the ureterovesical junction, while lower are those below the ureterovesical junction. It is important to treat acute obstructions because they cause stasis of urine flow that can increase risk for infection and calculi (stone) formation. Obstruction can also cause hydronephrosis, where the renal pelvis and calyces become dilated; or hydroureter, where the ureters become dilated due to increased fluid accumulation. The high pressures inside the ureter and renal pelvis can be transmitted back to the collecting ducts of the nephron and compress the renal vasculature, decreasing blood flow, leading to renal atrophy. The decrease in renal blood flow brings about a compensatory release of renin which causes hypertension in the patient.

    Urolithiasis is the process of stone formation in the urinary tract. The word “lith” comes from Greek and means “stone.” Other terms for stones located in the kidney include nephrolithiasis or renal calculi. If the stone is located in other parts of the urinary tract such as the ureter or bladder, then it’s known as ureterolithiasis or cystolithiasis.

    Watch the video Kidney Stones – Types, Formation, Treatment, Prevention

    There are several types of kidney stones: calcium containing, which may be calcium oxalate or calcium phosphate, magnesium ammonium phosphate (struvite), uric acid (urate), and cystine stones. The most common stone is calcium oxalate, followed by calcium phosphate, struvite, uric acid, and cystine. Calcium-oxalate, uric acid and cystine stones are more likely to form in acidic urine. Calcium – phosphate and struvite stones are more likely to form in alkaline urine.

    There are many factors that influence the formation of kidney stones, including: amounts of stone-forming constituents in the diet, predisposition for urinary tract infections, drugs, and genes. Any condition that increases concentration of potential kidney stone components in the urine increases the risk of formation.

    Calcium intake though calcium supplements or regular use of calcium-containing antacids can elevate calcium levels in the urinary tract and increases the risk of renal calculi.

    Oxalates are found in spinach, Swiss chard, cocoa, chocolate, pecans, peanuts, soy products, and other foods and increase the risk for calcium oxalate stone formation.

    Magnesium ammonium phosphate – Mg(NH4)PO4 (struvite or staghorn) stones form more common in women and especially in those with recurring UTIs. Certain bacteria use the enzyme urease to convert urea into ammonia which is basic. The more alkaline environment increases phosphate in the urine which combines with ammonium and magnesium ions to form stones.

    Urate stones form more commonly in those that have high plasma levels of uric acid (hyperuricemia). A drug used for gout called probenecid blocks urate reabsorption in the PCT and will increase urate levels in the urine which also increases the risk for urate stones. For this reason, it is especially important to drink lots of water while taking probnecid. Unlike other urinary stones, urate stones are not visible on X-ray films.

    Cystine stones are the least common type of renal calculi (less than 1% overall), but they represent a significant cause in children. These come about with genetic disorders that alter cystine reabsorption in the PCT to increase cystine levels in the urine (cystinuria). This higher concentration of cystine favors crystal formation.

    Kidney stones are more likely to occur in those that are older, but most people get their first stone before the age of fifty. Older people are more likely to be dehydrated and also express decreased levels of natural inhibitors of urolithiasis, such as citrate. Men have a greater risk compared to women, and of all Americans, Caucasians have the highest incidence of kidney stones.

    Obesity increases the risk for stones and is thought to be related to decreased mobility and/or dietary factors. Therefore to reduce risk of stone formation, especially in obese individuals, physical activity can enhance calcium retention in bone rather than filtration in the kidney and introduction into the urinary tract. Hydration also plays a role in reducing renal lithiasis by diluting the potential stone forming constituents within the urinary tract. On the other hand, and common among obese individuals, diets high in sodium increase calcium in the urine and excess animal protein acidifies the urine while also increasing uric acid levels in the urine; all of which increases risk of stone formation.

    CLICK HERE and read about the kidney stone belt.

    Those living in the “kidney stone belt” (southern united states) are at greater risk. Note that this area is also characterized by increased incidence of obesity. The increased incidence of kidney stones is thought to be due to the warmer weather which brings an increased risk for dehydration. Furthermore, the Southern diet on average features more oxalates found in iced tea, okra, and spinach, and tends to be high in sodium as well.

    Three naturally occurring inhibitors of urolithiasis help prevent stone formation even when the urine is concentrated with stone-forming components. These include citrate, magnesium, and Tamm-Horsfall mucoprotein. Citrate complexes with calcium in the urine prevent it from forming crystals. Magnesium, also a divalent ion, competes with calcium for binding with oxalate. Magnesium-oxalate is more soluble and less likely to form stones. Tamm-Horsfall mucoprotein (also called uromodulin) is a glycoprotein. It is produced by cells of the thick ascending limb of the loop of Henle. It enters the filtrate and appears to inhibit crystal formation, although the exact mechanism is not well known.

    Watch the video Inside Kidney Stone Disease.

    There are 3 major steps in the formation of kidney stones including nucleation, growth, and aggregation. Nucleation refers to ions such as calcium and oxalate coming together to form a solid crystal nidus, and this most often occurs in the collecting ducts. Between the collecting duct and renal pelvis, these crystals grow in size. In the renal pelvis, the crystals will aggregate with one another to form larger crystals and stones. At this point, they may leave the renal pelvis and travel into the ureter, or some stones may remain in the pelvis being restricted from entering the ureters due to size/shape. The ureters are 3-4 mm in diameter and if the stone is greater than this, passage down the ureter will elicit intense pain known as renal colic as the stone irritates the ureter, especially during intermittent ureter peristaltic movements (known as “passing a stone”). Renal colic is described as intermittent and excruciating and occurs in the flank and upper abdominal region on the affected side. Intense colicky pain is often associated with nausea and vomiting. In contrast, non-colicky pain is continuous, typically not as intense, and associated with a stone localized in the renal calyces or renal pelvis. Unlike colicky pain, non-colicky pain increases with movements, so patients attempt to remain very still. Non-colicky pain is similar to that associated with appendicitis or pancreatitis.

    Several measures can be taken to prevent urolithiasis. Perhaps most important is drinking lots of water and avoiding foods known to promote stone formation. For ureterolithiasis, tamsulosin (Flomax), an alpha-1 antagonist can be used to help dilate the ureter and help the stone pass. A strong NSAID like toradol (Ketorolac) or an opioid such as hydromorphone or morphine may be used for the intense intermittent pain. Anti-nausea drugs like ondansetron (Zofran) and promethazine (Phenergan) may be used to treat nausea and vomiting. To help prevent calcium stones, the physician may prescribe a thiazide diuretic. The image below can be used to understand the mechanism by which thiazide diuretics act to decrease calcium in the urine. Thiazide diuretics block Na+/Cl- symporters on the apical membrane of renal tubular cells in the DCT. This acts to decrease intracellular Na+ levels and thus increases the “driving force” for Na+ to move into the cell via Na+/Ca2+ antiporters on the basolateral membrane. This increased antiporter activity moves Ca2+ that enters the cell via TRPV5 channels on the apical membrane out of the cell, where it is then reabsorbed into the blood. For the stones that are more likely to form in an alkaline environment, attempts may be made to acidify the urine. Adding apple cider vinegar to the diet may help prevent stone formation. Sometimes medical procedures can be used to treat kidney stones:

    Image by Becy T. BYU-I S20

    Extracorporeal shock wave lithotripsy (ESWL) is a nonsurgical technique that may be used to break up large stones (>2 cm in diameter) into smaller fragments that can more easily be passed by the urinary system. This procedure involves the use of high frequency sound waves (ultrasound) targeted at the stone, breaking it up. It is painful to the patient if performed while awake, so it is generally done under spinal anesthesia. The patient is positioned in a water bath or lies on a cushion. ESWL is effective in disintegrating stones smaller than 30 mm 60-99% of the time and is not used for cystine stones.

    Ureteroscopy is ideal for medium sized stones in the ureter. This procedure is also done under general anesthesia and involves inserting a flexible-steerable ureteroscope into the bladder and then up into the ureters. A laser or pneumatic device is then used to pulverize the stone.

    Treatment for large stones (>20 mm), often requires a surgical procedure known as percutaneous nephrolithotomy, where a small hole is made in the back to access the kidney. A camera is inserted through the hole and allows for visualization of the stone which is then pulverized using ultrasound, lasers, or a pneumatic device.

    This content is provided to you freely by BYU-I Books.

    Access it online or download it at https://books.byui.edu/bio_381_pathophysiol/1213__obstructive_di.