Types of Crystals in Urine
Urine is a liquid waste product that is produced by the kidneys and excreted through the urinary tract. Urine contains various substances that are dissolved or suspended in water, such as salts, minerals, organic compounds, and cellular debris. Some of these substances can form solid particles or crystals in urine under certain conditions. These crystals can be seen under a microscope when a urine sample is examined.
Crystals in urine are not necessarily abnormal or indicative of disease. Some crystals are normal and harmless, and may be influenced by factors such as diet, hydration, medication, and urine pH. These crystals are usually small, few in number, and do not cause any symptoms or complications. Examples of normal crystals include calcium oxalate, calcium carbonate, and ammonium biurate.
However, some crystals in urine are abnormal and may signal an underlying disorder or problem in the urinary system. These crystals are usually large, numerous, and may cause pain, irritation, inflammation, infection, or obstruction in the urinary tract. Examples of abnormal crystals include cystine, tyrosine, leucine, bilirubin, and cholesterol.
The type and number of crystals in urine can vary depending on several factors, both in vivo (within the body) and in vitro (outside the body). In vivo factors include the concentration and solubility of crystallogenic substances in the urine, the urine pH, the diet of the individual, and the excretion of diagnostic imaging or therapeutic agents. In vitro factors include the temperature of the urine sample, the evaporation of water from the sample, the change in urine pH due to standing or bacterial overgrowth, and the presence of contaminants or additives in the sample.
Therefore, it is important to collect and handle urine samples properly for accurate identification and interpretation of crystals in urine. The following sections will describe some of the common types of crystals that can be found in urine, their characteristics, their causes, their clinical significance, and their detection and reporting methods.
Struvite crystals are one of the most common types of crystals found in urine from dogs and cats. They are also known as magnesium ammonium phosphate or triple phosphate crystals. They usually appear as colorless, three-dimensional, prism-like crystals that resemble coffin lids. They are usually large and can be easily seen under low magnification.
Struvite crystals can form in urine of any pH, but they are more likely to form in neutral to alkaline urine. This is because alkaline urine increases the availability of free ammonia, which is a component of struvite. Some bacteria that cause urinary tract infections can also produce urease, an enzyme that converts urea to ammonia and raises the urine pH. This can promote the formation of struvite crystals and stones in the urinary tract.
Struvite crystals are not always associated with disease. They can be seen in urine from healthy individuals, especially after a meal or when the urine is concentrated. However, if they are present in large numbers or accompanied by other signs of infection, such as bacteria, white blood cells, or blood, they may indicate a problem. Struvite crystals can cause irritation, inflammation, and obstruction of the urinary tract. They can also form large stones that may require surgical removal.
The treatment of struvite crystals depends on the underlying cause and the severity of the condition. If there is an infection, antibiotics may be prescribed to eliminate the bacteria and reduce the urine pH. If there are stones, dietary modification or surgery may be needed to dissolve or remove them. The prevention of struvite crystals involves maintaining a healthy urinary tract by providing adequate hydration, frequent urination, and appropriate diet.
Cystine crystals are hexagonal crystals that are derived from the amino acid cystine. They are usually colorless or yellow and can have equal or unequal sides. They tend to form in acidic urine and are often associated with a rare genetic disorder called cystinuria. Cystinuria is a condition in which the kidneys fail to reabsorb cystine and other amino acids from the urine, leading to excessive excretion of these substances. Cystine crystals can aggregate and form stones in the urinary tract, causing pain, hematuria, and obstruction. Cystine stones are resistant to dissolution and often require surgical removal.
Cystine crystals can be identified by their characteristic shape and solubility in hydrochloric acid. They can be distinguished from uric acid crystals, which are also common in acidic urine, by their lack of color and their resistance to acetic acid. Cystine crystals can also be confirmed by using a cyanide-nitroprusside test, which produces a purple-red color when cystine is present.
The diagnosis and management of cystinuria involves genetic testing, urine analysis, imaging studies, dietary modifications, hydration, medication, and surgery. The goals of treatment are to prevent stone formation, relieve symptoms, and preserve kidney function. Patients with cystinuria should drink plenty of fluids to dilute their urine and reduce the concentration of cystine. They should also avoid foods that are high in methionine, such as meat, eggs, cheese, and fish, as methionine is converted to cystine in the body. Medications such as alpha-mercaptopropionylglycine (tiopronin) or D-penicillamine can help bind cystine and increase its solubility in urine. However, these drugs can have serious side effects and require close monitoring. Surgery may be needed to remove large or recurrent stones that cannot be dissolved or passed spontaneously.
Cystine crystals are rare but important findings in urine microscopy. They indicate a metabolic disorder that can cause significant morbidity and mortality if left untreated. Therefore, it is essential to recognize and report these crystals and refer the patient for further evaluation and treatment.
Tyrosine crystals are yellow or dark coloured and look like needles massed together. They are insoluble in ethanol, ether, and acetone. They’re often found in acidic urine, and they may be caused by metabolic disorders like liver disease or tyrosinemia .
Tyrosinemia is a rare inherited disorder that affects the metabolism of tyrosine, an amino acid. It can lead to serious complications such as liver failure, kidney damage, neurological problems, and increased risk of liver cancer. Symptoms of tyrosinemia include difficulty gaining weight, fever, diarrhea, bloody stools, and vomiting .
Liver disease can also affect the breakdown of tyrosine and cause its accumulation in the urine. Liver disease can have various causes, such as viral infections, alcohol abuse, autoimmune disorders, or genetic conditions. Symptoms of liver disease may include jaundice, abdominal pain, swelling, nausea, fatigue, and bleeding .
Treatment for tyrosine crystals in urine depends on the underlying cause. For tyrosinemia, dietary restriction of tyrosine and phenylalanine (another amino acid) may be recommended, along with medication to inhibit the production of toxic metabolites. Liver transplantation may be required in severe cases. For liver disease, treatment may involve medication, lifestyle changes, or surgery depending on the type and stage of the condition.
Tyrosine crystals in urine are usually detected by microscopic examination of a urine sample. They can be distinguished from other types of crystals by their shape, color, and solubility properties. However, they may not always be visible or present in every urine sample from a person with a metabolic disorder. Therefore, other tests such as blood tests or genetic tests may be needed to confirm the diagnosis.
Tyrosine crystals in urine are not very common and usually indicate a serious medical condition that requires prompt attention. If you notice any symptoms of tyrosinemia or liver disease, or if you have a family history of these disorders, you should consult your doctor as soon as possible. Early diagnosis and treatment can help prevent complications and improve your quality of life.
Cholesterol crystals are clear, long rectangles with cut-out corners. They look like stained glass . They are most likely to appear after the urine sample has been refrigerated . Cholesterol crystals can be found in both neutral and acidic urine . They are insoluble in acids and alkalis but soluble in ether, ethanol, and chloroform.
Cholesterol crystals are rarely found except in severe kidney disease or when a lymphatic vessel has ruptured into the renal pelvis . They may be caused by renal tubular disease, which can lead to renal failure if left untreated. Renal tubular disease is a condition that affects the function of the tubules, the small tubes that carry urine from the kidneys to the bladder. Symptoms may include low urine output, swelling, fatigue, nausea, and confusion.
Treatment may involve alkali therapy to help treat chronic metabolic conditions, like renal tubular disease. Alkali therapy is the use of medications that increase the pH of the blood and urine, making them less acidic. This can help prevent kidney damage and improve kidney function. Other treatments may depend on the underlying cause of the kidney disease or lymphatic rupture.
Calcium carbonate crystals are variably sized crystals that frequently appear as large spheroids with radial striations. They can also be seen as smaller crystals with round to ovoid shapes . They are colorless to yellow-brown and can impart a brownish tinge to the urine, when they occur in high numbers.
Calcium carbonate crystals are not associated with disease, but they can sometimes be mistaken for bacteria. They occur in alkaline urine . Certain drugs, including sulfonamide antibiotics or contrast dyes used in medical imaging procedures can also form crystals in the urine.
A unique feature of calcium carbonate crystals is that they effervesce with hydrochloric acid or acetic acid. This can help to confirm the presence of calcium carbonate in the urine.
Calcium carbonate crystals are normal in urine and do not require any specific treatment. However, if they are accompanied by other types of crystals, such as calcium oxalate or calcium phosphate, they may indicate a risk of kidney stones. In that case, your doctor may recommend obtaining calcium through other means, like adding more dairy to your diet, instead of supplements. You may also need to drink more water and reduce your intake of salt, protein, and oxalate-rich foods.
Calcium carbonate crystals are variably sized crystals that frequently appear as large spheroids with radial striations. They can also be seen as smaller crystals with round to ovoid shapes. They are colorless to yellow-brown and can impart a brownish tinge to the urine, when they occur in high numbers.
Calcium carbonate crystals are not associated with disease, but they can sometimes be mistaken for bacteria. They occur in alkaline urine. Certain drugs, including sulfonamide antibiotics or contrast dyes used in medical imaging procedures can also form crystals in the urine.
A unique feature of calcium carbonate is that the crystals effervesce with hydrochloric acid or acetic acid. This can help to confirm the presence of calcium carbonate in the urine.
Crystals of calcium carbonate — which is a supplement you can take to get more calcium — are also frequently associated with kidney stones. If you have calcium carbonate crystals in your urine, your doctor may recommend obtaining calcium through other means, like adding more dairy to your diet, instead of supplements.
Calcium oxalate crystals are the most common type of kidney stone . They are formed when there is too much oxalate, a natural substance found in many foods, and too little liquid in the urine. Oxalate can bind with calcium and form crystals that can grow into stones.
Calcium oxalate crystals typically appear as colorless squares with intersecting lines, resembling an envelope . They can vary in size from very small to quite large and can be seen under a microscope . They can occur in urine of any pH, but they are more likely to form in acidic urine .
Some of the factors that can increase the risk of calcium oxalate crystals and stones are :
- Dehydration from not drinking enough water
- A diet high in protein, salt, sugar, or oxalate-rich foods, such as spinach, rhubarb, nuts, chocolate, tea, and coffee
- Medical conditions that affect the absorption of calcium or oxalate, such as inflammatory bowel disease, gastric bypass surgery, hyperparathyroidism, or cystinuria
- Medications that contain calcium or oxalate, such as vitamin C supplements, antacids, diuretics, or antibiotics
Calcium oxalate crystals and stones can cause various symptoms depending on their size and location. Some of the possible symptoms are :
- Pain in the back, side, abdomen, or groin
- Blood in the urine (hematuria)
- Cloudy or foul-smelling urine
- Nausea and vomiting
- Fever and chills
- Urinary urgency and frequency
- Difficulty urinating or passing urine
The treatment of calcium oxalate crystals and stones depends on their size and severity. Some of the possible treatments are :
- Drinking plenty of water to flush out the crystals and stones
- Taking pain relievers to ease the discomfort
- Taking medications that can help dissolve or prevent the formation of crystals and stones, such as potassium citrate, thiazide diuretics, or allopurinol
- Undergoing procedures that can break up or remove the stones, such as shock wave lithotripsy (SWL), ureteroscopy (URS), percutaneous nephrolithotomy (PCNL), or open surgery
The prevention of calcium oxalate crystals and stones involves modifying some of the risk factors that can cause them. Some of the preventive measures are :
- Drinking enough water to keep the urine clear and dilute
- Reducing the intake of protein, salt, sugar, and oxalate-rich foods
- Increasing the intake of calcium-rich foods or supplements to bind with oxalate and reduce its absorption
- Maintaining a healthy weight and exercising regularly
- Treating any underlying medical conditions that can affect the metabolism of calcium or oxalate
Ammonium biurate crystals are variably sized crystals that frequently appear as yellowish-brown spheres with spiky projections. They are sometimes called "thorny apple" crystals because of their shape . They can also be seen as smaller, smooth spheres.
Ammonium biurate crystals are often found in normal urine, especially in dogs and cats . They can occur in urine of any pH, but their formation is favored in alkaline urine . They are usually harmless and do not indicate any disease or disorder .
However, the presence of ammonium biurate crystals, especially in large numbers or in combination with a high urine pH (9.0 or higher), may indicate an old or poorly preserved urine specimen. In this case, the urine analysis results may not be reliable and a fresh urine sample may be needed for accurate testing. Therefore, it is important to collect and store urine samples properly and perform the analysis as soon as possible.
Ammonium biurate crystals are soluble in acetic acid and can be distinguished from calcium carbonate crystals, which are also brown spheres, by this method . They can also be differentiated from cystine crystals, which are yellow hexagons, by their shape and solubility.
Leucine crystals are yellow-brown disks with concentric rings like a tree trunk. They are insoluble in ethanol, ether, and acetone. They are typically not found in healthy urine. They are found in acidic urine.
Leucine crystals may be seen in liver disorders in which amino acid metabolism is impaired. They can indicate leucinosis — a rare inherited disorder — also called the “maple syrup urine disease”. They can also suggest Hartnup disease, which is the inability to absorb certain protein building blocks, specifically leucine.
Symptoms of leucinosis include lethargy, vomiting, and a maple syrup smell in urine and sweat. Symptoms of Hartnup disease include skin rashes, neurological problems, and psychiatric disorders.
Treatment of leucinosis involves dietary restriction of leucine and supplementation of other amino acids. Treatment of Hartnup disease involves increasing the intake of niacin and tryptophan.
Leucine crystals are rare and usually indicate a serious medical condition. They should be reported to a physician for further evaluation and management.
Amorphous crystals are not really crystals in the strict sense, but rather aggregates of finely granular material that have no definite shape under the light microscope. They can be composed of different substances, such as urates, phosphates or xanthine, depending on the urine pH and solubility. Amorphous crystals are usually small and can only be observed at high magnification, unless they are present in large amounts. They may resemble bacteria or other cellular debris, but can be distinguished by gram-staining or polarized light microscopy.
Amorphous crystals have no specific clinical significance and are often seen in normal urine. They may form due to changes in urine concentration, temperature or pH during storage or transport. They may also result from the degeneration of other crystals or cells. Therefore, it is important to collect and examine urine samples as fresh as possible to avoid false interpretations.
Some examples of amorphous crystals are:
- Amorphous urates: These are yellow-brown granules that are commonly seen in acidic urine. They may precipitate when the urine cools or becomes more concentrated. They are soluble in warm water and alkali. They may be associated with high protein intake, fever, gout or dehydration.
- Amorphous phosphates: These are colorless granules that are commonly seen in alkaline urine. They may precipitate when the urine becomes more alkaline due to bacterial growth or dietary factors. They are soluble in acetic acid. They may be associated with urinary tract infection, renal calculi or alkaline diet.
- Amorphous xanthine: These are rare and very small granules that are seen in acidic urine. They may precipitate due to inherited disorders of purine metabolism or treatment with xanthine oxidase inhibitors. They are insoluble in water and acid. They may be associated with xanthinuria, allopurinol therapy or chemotherapy.
Besides the common types of crystals mentioned above, there are some other crystals that may be occasionally seen in urine samples. These include:
Sulfonamide crystals: These are colorless or yellow-brown crystals that may have various shapes, such as needles, plates, sheaves, or rosettes. They are formed from the precipitation of sulfonamide drugs or their metabolites in the urine. Sulfonamide drugs are antibiotics that are used to treat infections caused by bacteria. Sulfonamide crystals may cause irritation, inflammation, or obstruction of the urinary tract, leading to symptoms such as hematuria (blood in urine), dysuria (painful urination), or oliguria (reduced urine output). Sulfonamide crystals can be prevented by increasing fluid intake, alkalinizing the urine, and reducing the dose or duration of sulfonamide therapy.
Indinavir crystals: These are colorless or pale yellow crystals that may have various shapes, such as starbursts, rectangular plates, fans, or needles. They are formed from the precipitation of indinavir, a drug that is used to treat HIV infection. Indinavir crystals may cause nephrolithiasis (kidney stones), nephrotoxicity (kidney damage), or crystalluria (crystals in urine). Indinavir crystals can be prevented by increasing fluid intake, taking indinavir with food, and avoiding other drugs that may increase the risk of crystal formation.
Uric acid crystals: These are yellow or pink-brown crystals that may have various shapes, such as rhomboids, rosettes, or whetstones. They are formed from the precipitation of uric acid, a waste product of purine metabolism. Uric acid crystals may be associated with conditions such as gout (a type of arthritis caused by high uric acid levels), hyperuricemia (high uric acid levels in blood), or uric acid nephrolithiasis (uric acid kidney stones). Uric acid crystals can be prevented by increasing fluid intake, alkalinizing the urine, and reducing the intake of purine-rich foods (such as meat, seafood, and alcohol).
Crystals in urine can be detected by microscopic examination of a urine sample. A fresh urine sample should be collected in a clean container and centrifuged to obtain a sediment. The sediment should be resuspended in a small amount of urine and placed on a glass slide with a coverslip. The slide should be examined under a light microscope at different magnifications.
The identification of crystals in urine is based on their shape, color, size, and solubility. Some common types of crystals and their characteristics are:
- Struvite crystals: colorless, three-dimensional prisms with oblique ends ("coffin lids")
- Cystine crystals: colorless or yellow, hexagonal plates or needles
- Cholesterol crystals: clear, rectangular plates with notched corners
- Tyrosine crystals: yellow or brown, fine needles in clusters or rosettes
- Bilirubin crystals: yellow or brown, granular or needle-like
- Calcium carbonate crystals: colorless or yellow-brown, spherical or dumbbell-shaped with radial striations
- Calcium oxalate crystals: colorless, envelope-shaped squares or bipyramidal octahedra
- Ammonium biurate crystals: yellow-brown, spherical with spiny projections ("thorn apples")
- Leucine crystals: yellow-brown, round disks with concentric rings
- Amorphous crystals: granular aggregates without definite shape
Some crystals may resemble other substances or cells in urine, such as bacteria, mucus, red blood cells, or white blood cells. To distinguish them, additional tests may be performed, such as Gram staining, polarized light microscopy, or chemical solubility tests.
The reporting of crystals in urine should include the type and quantity of the crystals observed. The quantity can be estimated as few, moderate, or many per high-power field (HPF) or low-power field (LPF), depending on the size of the crystals. For example:
- Few struvite crystals per LPF
- Moderate cystine crystals per HPF
- Many calcium oxalate crystals per HPF
The presence and type of crystals in urine may have clinical significance depending on the patient`s history, symptoms, and other laboratory findings. Some crystals may indicate metabolic disorders, urinary tract infections, kidney stones, drug toxicity, or liver disease. Therefore, the interpretation of urinary crystals should be done by a qualified health professional in conjunction with other relevant information.
The formation and appearance of urinary crystals depend on various factors, both in vivo (within the body) and in vitro (outside the body). Some of these factors are:
In vivo factors
Concentration and solubility of crystallogenic substances contained in the specimen: The higher the concentration and the lower the solubility of a substance in urine, the more likely it is to form crystals. For example, cystine and uric acid have low solubility in acidic urine and tend to form crystals when their concentration exceeds a certain threshold. Conversely, struvite and calcium carbonate have higher solubility in alkaline urine and are less likely to crystallize unless there is an infection or a metabolic disorder that increases their production.
Urine pH: The acidity or alkalinity of urine affects the solubility and charge of crystallogenic substances. For example, calcium oxalate is more soluble in acidic urine than in alkaline urine, whereas struvite is more soluble in alkaline urine than in acidic urine. Therefore, urine pH can influence the type and amount of crystals that form in urine.
Diet: The intake of certain foods and beverages can affect the concentration and pH of urine and thus the formation of crystals. For example, foods high in protein, purine, or oxalate can increase the production of uric acid, cystine, or oxalate in urine, respectively. These substances can then form crystals if their concentration exceeds their solubility. On the other hand, foods high in citrate or magnesium can inhibit the formation of calcium oxalate or struvite crystals by binding to calcium or phosphate ions and preventing them from crystallizing.
Excretion of diagnostic imaging and therapeutic agents: Some drugs or contrast agents used for medical purposes can be excreted in urine and form crystals. For example, sulfonamides, indinavir, acyclovir, and triamterene are some medications that can cause crystalluria. Similarly, radiopaque contrast agents used for X-ray imaging can precipitate in urine and form crystals.
In vitro factors
Temperature: The solubility of most substances decreases as the temperature decreases. Therefore, cooling of urine samples can cause some substances to crystallize out of solution. For example, uric acid and calcium oxalate are more likely to form crystals when urine samples are refrigerated.
Evaporation: The evaporation of water from urine samples can increase the concentration of solutes and decrease their solubility. This can result in the formation of crystals that may not have been present in fresh urine samples. For example, ammonium biurate and calcium carbonate are more likely to form crystals when urine samples are left uncovered for a long time.
Urine pH: The pH of urine samples can change over time due to bacterial growth or chemical reactions. This can affect the solubility and charge of crystallogenic substances and alter the type and amount of crystals that form in urine. For example, urease-producing bacteria can hydrolyze urea into ammonia and carbon dioxide, which can raise the pH of urine and favor the formation of struvite and calcium carbonate crystals.
Therefore, it is important to collect, store, and analyze urine samples properly to avoid artifacts or misinterpretations caused by these factors. Urine samples should be collected in clean containers with tight lids and analyzed as soon as possible after collection. If analysis is delayed, urine samples should be refrigerated or preserved with appropriate chemicals to prevent bacterial growth or chemical changes. Urine samples should also be examined under different magnifications and lighting conditions to identify different types of crystals accurately.
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