Friday 2 November 2012

EPITHELIAL CELLS IN URINE

YEAST IN URINE



WBC IN URINE


BACTERIA IN URINE



CASTS IN URINE

Hyaline casts
Hyaline casts are formed in the absence of cells in the tubular lumen. They consist of Tamm-Horsfall protein and have a smooth texture and a refractive index very close to that of the surrounding fluid. They are very difficult to see in wet preparations of urine and must be distinguished from mucus strands. Generally, hyaline casts have parallel sides with clear margins and blunted ends, whereas mucus strands are more variable in size with irregular margins (see below). Reduced lighting is essential to see hyaline casts in urine sediment preparations. Lighting can be reduced by lowering the substage condenser (or close the iris diaphragm). Hyaline casts are also easier to see if other particles (fat, debris) are caught up within them (see image on the left below). Hyaline casts are far easier to visualize using phase contrast microscopy (see image on the right below), but this is not available on standard microscopes.Note that when fat droplets stick to hyaline casts, they are still called hyaline and not fatty casts.
hyaline castphase cast
Hyaline casts (black arrows) in a wet preparation of urine sediment as visualized with the condenser racked down or the iris diaphragm closed.Hyaline casts (indicated by the black arrow) as seen under phase contrast microscopy. The edges of the cast are easier to see with this technique.
mucusmucus phase
Mucus strands (arrow) are mostly seen in urine form horses. They mimic casts, however they often have irregular borders, fold over, and taper at one or both endsA phase contrast image of mucus strands. Tapering ends are evident in several of the strands (arrow), which are also more wavy and fold over compared to hyaline casts

Hyaline casts can be present in low numbers (0-1/LPF) in concentrated urine of otherwise normal patients and are not always associated with renal disease.

Greater numbers of hyaline casts may be seen in association with proteinuria of renal (e.g., glomerular disease) or extra-renal (e.g., overflow proteinuria as in myeloma) origin. In such cases it has been proposed that the presence of excessive serum protein in the tubular lumen promotes precipitation of the Tamm-Horsefall mucoprotein.


Cellular castscellular cast
Cellular casts most commonly result when disease processes such as ischemia, infarction, or nephrotoxicity cause degeneration and necrosis of tubular epithelial cells. The presence of these casts indicates acute tubular injury but does not indicate the extent or reversibility of the injury.
A common scenario is the patient with decreased renal perfusion and oliguria secondary to severe dehydration. Ischemic injury results in degeneration and sloughing of the epithelial cells. The resulting casts often are prominent in urine produced following rehydration with fluid therapy. The restoration of urine flow "flushes" numerous casts out of the tubules.
Leukocytes can also be incorporated into casts in cases of tubulo-interstitial inflammation (eg, pyelonephritis). It is rarely possible to distinguish between epithelial casts and leukocyte casts in routine sediment preparations, however, since nuclear detail is obscured by the degenerated state of the cells.

Granular casts

granular cast
Granular casts, as the name implies, have a textured appearance which ranges from fine to coarse in character. Since they usually form as a stage in the degeneration of cellular casts, the interpretation is the same as that described for cellular casts. Low numbers of granular casts may be seen in the urine of animals without tubular injury, so the presence of casts should be interpreted along with clinical signs, rest of the urinalysis results, biochemistry results and other pertinent diagnostic information.

"Fatty" casts

fatty cast
Fatty casts are identified by the presence of refractile lipid dropletswithin the protein matrix of the cast. The background matrix of the cast may be hyaline or granular in nature. Fatty casts, like granular casts, are thought to represent tubular degeneration. Note that the term fatty cast is not used for hyaline casts with fat droplets adhered to them (which are frequently seen in urines in which free lipid droplets are present as well). Pictured on the right is a fatty cast with a hyaline matrix. Also notice the free lipid droplets in the background.
feline renal epithelium
Feline proximal renal tubular epithelial cells contain numerous fat droplets (100x oil immersion, Wright's stain)
Free lipid can be a normal finding in animal urine (as an isolated finding, lipiduria is seldom of clinical significance) and is likely from degeneration of sloughed renal tubular or transitional epithelial cells. Shedding of these cells in urine can occur under physiologic (low numbers can be shed in healthy animals) or pathophysiologic (renal tubular injury) conditions. Once liberated from degenerating or ruptured cells, fat frequently sticks to hyaline casts. This may happen more in cats, because their renal tubular epithelium can normally contain small to moderate amounts of fat (see image to the left). Differentiation of true fatty casts from hyaline casts with adherent fat can be difficult and is based on the character of the cast matrix, rather than on the lipid content per se.

Waxy casts

waxy
Waxy casts have a smooth consistency but are more refractile and therefore easier to see in a regular wet sediment preparation of urine compared to hyaline casts. They commonly have squared off ends, as if brittle and easily broken, and also have smooth parallel-sided borders.
Waxy casts indicate tubular injury of a more chronic nature than granular or cellular casts and are always of pathologic significance.
Illustrated to the right is urine from a dog with acute and chronic renal tubular injury as shown by the presence of waxy and coarse granular casts in the urine.









StruviteStruvite crystals (magnesium ammonium phosphate, triple phosphate) usually appear as colorless, 3-dimensional, prism-like crystals ("coffin lids"). Occasionally, they instead resemble (vaguely) an old-fashioned double-edged razor blade (lower frame).
Struvite crystals are the most common type in urine from dogs and cats. They are often seen in urine from clinically normal individuals. Though they can be found in urine of any pH, their formation is favored in neutral to alkaline urine.
Urinary tract infection with urease-positive bacteria can promote struvite crystalluria (and urolithiasis) by raising urine pH and increasing free ammonia.

Bilirubin

bilirubin
Bilirubin crystals form from conjugated bilirubin (water soluble) and are needle-like to granular crystals that are yellow in color. They tend to precipitate onto other formed elements in the urine. In the top picture, fine needle-like crystals have formed on an underlying cell. This is the most common appearance of bilirubin crystals. In the lower two pictures, cylindrical bilirubin crystals have formed in association with droplets of fat, resulting in a "flashlight" appearance. This form is less commonly seen.
Bilirubin crystals are seen most commonly in canine urine, especially in highly concentrated specimens. They are less common in urine of other species. In dogs, they often are of no clinical significance (healthy dogs can have low, but detectable, bilirubin levels in urine). Bilirubin crystals (or a positive chemical reaction on the urine dipstick) in feline, equine, bovine, or camelid urine is an abnormal finding and the animal should be investigated for an underlying cholestatic process.

Calcium carbonate

calcium carbonate
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, ovoid, or dumbbell shapes. they are colorless to yellow-brown and can impart a brownish tinge to the urine, when they occur in high numbers.
These crystals are common in the urine of normal horses, rabbits, guinea pigs and goats. They have not been observed in canine or feline urines.

"Amorphous" crystals

amorphous
"Amorphous" crystals appear as aggregates of finely granular material without any defining shape at the light microscopic level. They can be comprised of urates, phosphates or xanthine. Amorphous urates (Na, K, Mg, or Ca salts) tend to form in acidic urine and may have a yellow or yellow-brown color. Amorphous phosphates are similar in general appearance, but tend to form in alkaline urine and lack color. Xanthine crystals are usually in the form of "amorphous" crystals. These crystals occur in Dalmations on allopurinol therapy for urate urolithiasis.
Generally, no specific clinical interpretation can be made based on the finding of amorphous crystals. Small amorphous crystals can be confused with bacterial cocci in some cases, but can be distinguished by Gram-staining. Degenerating crystals or cells can also resemble "amorphous" crystals.

Calcium oxalate dihydrate crystals

dihydrate
Calcium oxalate dihydrate crystals typically are colorless squares whose corners are connected by intersecting lines (resembling an envelope). They can occur in urine of any pH. The crystals vary in size from quite large to very small. In some cases, large numbers of tiny oxalates may appear as amorphous unless examined at high magnification.
These crystals are often seen in normal urine from domestic animals and can also be an artifact of storage (they can develop in stored urine), emphasizing the need to perform a urinalysis on fresh urine samples.
Urolithiasis due to calcium oxalate has been reported in both dogs and cats. In some cases, they occur secondary to abnormal calcium (increased) excretion due to disorders of calcium metabolism (e.g. hyperparathyroidism). Miniature Schnauzers are predisposed to calcium oxalate urolithiasis, despite no abnormalities in urinary calcium excretion.
Calcium oxalate dihydrate crystals can also be seen in cases of ethylene glycol intoxication, although the picket-shaped form of calcium oxalate monohydrate are pathognumonic. If seen in large numbers in the urine of a dog or cat with acute renal failure and other appropriate clinical signs, consideration should be given to this diagnosis.

Calcium oxalate monohydrate

monohydrate
Calcium oxalate monohydrate crystals vary in size and may have a spindle, oval, or dumbbell shape (for examples, see the two unlabeled crystals in the lower left corner of the image to the right). These forms of calcium oxalate monohydrate indicate supersaturation of the urine with calcium and oxalate and, along with calcium oxalate dihydrate crystals ("square envelopes"), can be seen in the urine of animals that have no urologic problems or those suffering from oxalate urolithiasis, hypercalciuric or hyperoxaluric disorders, or rarely ethylene glycol toxicosis. They are infrequent in the urine of normal dogs and cats but can be seen commonly in the urine from healthy horses.
A particular form of calcium oxalate monohydrate are flat, elongated, six-sided crystals ("picket fences") which are the larger crystals in the image above (which represents urine from a dog with ethylene glycol toxicosis). The arrow in the photo indicates a "daughter" crystal forming on the face of a larger underlying crystal. These "picket fence" forms of calcium oxalate monohydrate are frequently associated with ethylene glycol intoxication in dogs and cats, but are not always observed in the urine of affected animals (i.e. not 100% sensitive). They can also be seen in the urine of animals with hypercalciuria from other causes, e.g. paraneoplastic hypercalcemia with lymphoma.hempseed
Another rare form of calcium oxalate monohydrate are the "hempseed" variant or "orzo" (as in the pasta shape). The image on the right is from the urine of a dog with many of these crystals. The dog did not have ethylene glycol poisoning and the crystals are assumed to be secondary to supersaturation of the urine with calcium and oxalates, which precipitated in the acidic urine.

Ammonium biurate

biurate
Ammonium urate (or biurate) crystals generally appear as brown or yellow-brown spherical bodies with irregular protrusions ("thorn-apples"). In some urine samples, they do not have irregular protrusions but have smooth borders and can resemble calcium carbonate (although these do not occur in the urine from dogs and cats). Though possible in urine of any pH, their formation is favored in neutral to alkaline urine. They are frequently seen with amorphous urates.
These crystals are fairly common in dogs and cats with congenital or acquired portal vascular anomalies, with or without concomitant ammonium urate uroliths. They can be seen in urine from normal Dalmatians and Bulldogs, both of which .are predisposed to urate urolithiasis. They are rarely, if ever, seen in urine from normal cats or dogs of other breeds and have not been reported in large animals.

Cystine

cystine
Cystine crystals are flat colorless plates and have a characteristic hexagonal shape with equal or unequal sides. They often aggregate in layers. Their formation is favored in acidic urine.
Cystine crystalluria or urolithiasis is an indication of cystinuria, which is an inborn error of metabolism involving defective renal tubular reabsorption of certain amino acids including cystine. Sex-linked inheritance is suspected since male dogs are almost exclusively affected. Many breeds, as well as mongrels, have been reported affected . Renal function otherwise appears to be normal and, aside from a tendency to form uroliths, the defect is without serious consequence.

Drug crystals

sulfa
Many drugs excreted in the urine have the potential to form crystals. Hence, a review of the patients drug history is prudent when faced with unidentified urine crystals.
Most common among these are the sulfa drugs. Both panels on the right are from patients receiving trimethoprim-sulfadiazine. The differing appearance may relate to variation in drug concentration, urine pH, and other factors. The upper panel is from a feline case, the lower from a horse. The inset in the lower panel shows the crystals as they appeared when polarized.
Other examples include radiopaque contrast agents (Hypaque, Renografin) and ampicillin which may precipitate in acid urine as fine needle-like crystals (not shown).

Other crystals

melamine
We frequently see several different types of crystals that are of uncertain origin (see urine sediment atlas for examples). Whenever an "unknown" crystal is encountered, we usually perform solubility studies (chemical, i.e. hydrochloric acid, glacial acetic acid and sodium hydroxide, or heat) to help identify the crystals. Some crystals, such as uric acid, calcium phosphate and sulfa drug-related crystals have specific solubility characteristics which, with their shape and pH of the urine (and of course, clinical history), can aid in their identification. Sometimes, despite doing these solubility studies, the identity of the crystal remains a mystery. The clinical relevance of such crystals is questionable, but drug or chemical toxicity should always be considered in an animal presenting with clinical signs of renal failure and unidentified crystals in the urine. The crystals shown in the image above were seen in the urine of a cat with acute renal failure due to melamine toxicosis. These crystals were highly characteristic of melamine and facilitated diagnosis in affected animals.




Urine Test

URINE ANALYSIS


More than 100 different tests can be done on urine. A regular urinalysis often includes the following tests



  • Color. Many things affect urine color, including fluid balance, diet, medicines, and diseases. How dark or light the color is tells you how much water is in it. Vitamin B supplements can turn urine bright yellow. Some medicines, blackberries, beets, rhubarb, or blood in the urine can turn urine red-brown.
  • Clarity. Urine is normally clear. Bacteria, blood, sperm, crystals, or mucus can make urine look cloudy.
  • Odor. Urine does not smell very strong, but has a slightly "nutty" odor. Some diseases cause a change in the odor of urine. For example, an infection with E. coli bacteria can cause a bad odor, while diabetes or starvation can cause a sweet, fruity odor.
  • Specific gravity. This checks the amount of substances in the urine. It also shows how well the kidneys balance the amount of water in urine. The higher the specific gravity, the more solid material is in the urine. When you drink a lot of fluid, your kidneys make urine with a high amount of water in it which has a low specific gravity. When you do not drink fluids, your kidneys make urine with a small amount of water in it which has a high specific gravity.
  • pH. The pH is a measure of how acidic or alkaline (basic) the urine is. A urine pH of 4 is strongly acidic, 7 is neutral (neither acidic nor alkaline), and 9 is strongly alkaline. Sometimes the pH of urine is affected by certain treatments. For example, your doctor may instruct you how to keep your urine either acidic or alkaline to prevent some types of kidney stones from forming.
  • Protein. Protein is normally not found in the urine. Fever, hard exercise,pregnancy, and some diseases, especially kidney disease, may cause protein to be in the urine.
  • Glucose. Glucose is the type of sugar found in blood. Normally there is very little or no glucose in urine. When the blood sugar level is very high, as in uncontrolleddiabetes, the sugar spills over into the urine. Glucose can also be found in urine when the kidneys are damaged or diseased.
  • Nitrites. Bacteria that cause a urinary tract infection (UTI) make an enzyme that changes urinary nitrates to nitrites. Nitrites in urine show a UTI is present.
  • Leukocyte esterase (WBC esterase). Leukocyte esterase shows leukocytes (white blood cells [WBCs]) in the urine. WBCs in the urine may mean a UTI is present.
  • Ketones. When fat is broken down for energy, the body makes substances called ketones (or ketone bodies). These are passed in the urine. Large amounts of ketones in the urine may mean a very serious condition, diabetic ketoacidosis, is present. A diet low in sugars and starches (carbohydrates), starvation, or severe vomiting may also cause ketones to be in the urine.
  • Microscopic analysis. In this test, urine is spun in a special machine (centrifuge) so the solid materials (sediment) settle at the bottom. The sediment is spread on a slide and looked at under a microscope. Things that may be seen on the slide include:
    • Red or white blood cells. Blood cells are not found in urine normally. Inflammation, disease, or injury to the kidneys, ureters, bladder, or urethra can cause blood in urine. Strenuous exercise, such as running a marathon, can also cause blood in the urine. White blood cells may be a sign of infection or kidney disease.
    • Casts. Some types of kidney disease can cause plugs of material (called casts) to form in tiny tubes in the kidneys. The casts then get flushed out in the urine. Casts can be made of red or white blood cells, waxy or fatty substances, or protein. The type of cast in the urine can help show what type of kidney disease may be present.
    • Crystals. Healthy people often have only a few crystals in their urine. A large number of crystals, or certain types of crystals, may mean kidney stones are present or there is a problem with how the body is using food (metabolism).
    • Bacteria, yeast cells, or parasites. There are no bacteria, yeast cells, orparasites in urine normally. If these are present, it can mean you have an infection.
    • Squamous cells. The presence of squamous cells may mean that the sample is not as pure as it needs to be. These cells do not mean there is a medical problem, but your doctor may ask that you give another urine sample.


Urine test results
Color
Normal:
Pale to dark yellow
Abnormal:
Many foods and medicines can affect the color of the urine. Urine with no color may be caused by long-term kidney disease or uncontrolled diabetes. Dark yellow urine can be caused by dehydration. Red urine can be caused by blood in the urine.
Clarity
Normal:
Clear
Abnormal:
Cloudy urine can be caused by pus (white blood cells), blood (red blood cells), sperm, bacteria, yeast, crystals, mucus, or a parasite infection, such as trichomoniasis.
Odor
Normal:
Slightly "nutty" odor
Abnormal:
Some foods (such as asparagus), vitamins, and antibiotics (such as penicillin) can cause urine to have a different odor. A sweet, fruity odor may be caused by uncontrolled diabetes. A urinary tract infection (UTI) can cause a bad odor. Urine that smells like maple syrup can mean maple syrup urine disease, when the body cannot break down certain amino acids.
Specific gravity
Normal:
1.005-1.030
Abnormal:
A very high specific gravity means very concentrated urine, which may be caused by not drinking enough fluid, loss of too much fluid (excessive vomiting, sweating, or diarrhea), or substances (such as sugar or protein) in the urine. Very low specific gravity means dilute urine, which may be caused by drinking too much fluid, severe kidney disease, or the use of diuretics.
pH
Normal:
4.6-8.0
Abnormal:
Some foods (such as citrus fruit and dairy products) and medicines (such as antacids) can affect urinepH. A high (alkaline) pH can be caused by severe vomiting, a kidney disease, some urinary tract infections, and asthma. A low (acidic) pH may be caused by severe lung disease (emphysema), uncontrolled diabetes, aspirin overdose, severe diarrhea, dehydration, starvation, drinking too much alcohol, or drinking antifreeze (ethylene glycol).
Protein
Normal:
None
Abnormal:
Protein in the urine may mean kidney damage, an infection, cancerhigh blood pressure, diabetes,systemic lupus erythematosus (SLE), orglomerulonephritis is present.
Protein in the urine may also mean that heart failureleukemia, poison (lead or mercury poisoning), or preeclampsia (if you are pregnant) is present.
Glucose
Normal:
None
Abnormal:
Intravenous (IV) fluids can cause glucose to be in the urine. Too much glucose in the urine may be caused by uncontrolled diabetes, an adrenal glandproblem, liver damage, brain injury, certain types of poisoning, and some types of kidney diseases. Healthy pregnant women can have glucose in their urine, which is normal during pregnancy.
Ketones
Normal:
None
Abnormal:
Ketones in the urine can mean uncontrolled diabetes, a very low-carbohydrate diet, starvation or eating disorders (such as anorexia nervosa orbulimia), alcoholism, or poisoning from drinking rubbing alcohol (isopropanol). Ketones are often found in the urine when a person does not eat (fasts) for 18 hours or longer. This may occur when a person is sick and cannot eat or vomits for several days. Low levels of ketones are sometimes found in the urine of healthy pregnant women.
Microscopic analysis
Normal:
Very few or no red or white blood cells or casts are seen. No bacteria, yeast cells, parasites, or squamous cells are present. A few crystals are normally seen.
Abnormal:
Red blood cells in the urine may be caused by kidney or bladder injury, kidney stones, a urinary tract infection (UTI), inflammation of the kidneys (glomerulonephritis), a kidney or bladder tumor, or systemic lupus erythematosus (SLE). White blood cells (pus) in the urine may be caused by a urinary tract infection, bladder tumor, inflammation of the kidneys, systemic lupus erythematosus (SLE), or inflammation in the vagina or under the foreskin of the penis.
Depending on the type, casts can mean inflammation or damage to the tiny tubes in the kidneys, poor blood supply to the kidneys, metal poisoning (such as lead or mercury), heart failure, or a bacterial infection.
Large amounts of crystals, or certain types of crystals, can mean kidney stones, damaged kidneys, or problems with metabolism. Some medicines and some types of urinary tract infections can also increase the number of crystals in urine.
Bacteria in the urine mean a urinary tract infection (UTI). Yeast cells or parasites (such as the parasite that causes trichomoniasis) can mean an infection of the urinary tract.
The presence of squamous cells may mean that the sample is not as pure as it needs to be. These cells do not mean there is a medical problem, but your doctor may ask that you give another urine sample.