A3. Urologic laboratory examination. Urinalysis and urine culture

Urine culture

Urine culture refers to sending a urine sample for a bacterial culture. This gives the name of the causative bacteria as well as any antibiotic resistance. Urine culture is recommended to perform in all cases of pyelonephritis and most cases of lower urinary tract infection. It takes a few days to recieve the results.

Urinalysis

Urinalysis, also called urine analysis refers to any analysis of the urine.

A urine dipstick test, sometimes abbreviated as urinary stick or u-stix is a point-of-care test which is used to analyse certain parametres of the urine. It's quick and cheap, and can be read off manually or by automatic machines. They're used in the diagnosis and follow-up of many disorders, like urinary tract infection, diabetes mellitus, and chronic kidney disease. A normal dipstick evaluates the following parametres in the urine:

• Leukocytes
• Nitrate
• Protein
• Glucose
• Ketones
• Haemoglobin

The test is semiquantitative. This means that it cannot exactly tell the amount of the above compounds are present in the sample, but the degree of colour changes corresponds roughly to the amount.

Urinary sample collection

Proper sample collection is essential to maintain as high sensitivity and specificity as possible. A sterile container for urine collection is obligatory to prevent contamination. The patient should not provide a sample if they've peed in the previous 4 hours, as in these cases the urine is "too fresh" to show signs of bacterial infection. Morning urine is usually best. The male should withdraw the foreskin and the female should spread the labia when making the sample, to prevent contamination. The initial urine should be discarded; mid-stream urine should be used.

Procedure

This shows the urinary dipstick and the standard with which the result is compared to.

The patient provides a urinary sample. If the urine is to be analysed at a lab, the sample is sent to the lab.

If the urine is to be analysed with a dipstick, a single-use paper strip is dipped into the urine. The strip contains multiple squares covered with different reagents, each of which change colour when coming into contact with certain compounds in the urine. The degree of colour change is compared to a standard which is usually printed on the bottle.

Leukocytes

The presence of leukocytes in the urine, leukocyturia, is a sign of infection or bacterial colonisation in the urinary tract, or contamination from the vagina or penis.

If the urine sample was collected optimally, the sensitivity for upper or lower urinary tract infection in case of leukocyturia is approximately 80%, but it can also be positive in case of other pathologies in the urinary tract, like tumours or kidney stones.

Nitrite

In a healthy person, the urine contains no nitrite. Many bacteria, especially gram negatives, reduce nitrate in the urine to nitrite. Because not all bacteria causing urinary tract infection reduce nitrate, the test is not particularly sensitive (approx 50%), but assuming optimal sample collection, it's quite specific (90%).

Nitrate is found in the urine usually from dietary intake of vegetables. Lack of vegetables in the diet reduces the amount of nitrate in the urine, and as a result, the amount of nitrite and the sensitivity of the test as well.

The urine sample must be taken at least 4 hours after the previous bladder emptying, as bacteria in the bladder require a few hours to reduce nitrate to nitrite.

Protein

The urine dipstick actually measures albumin and not all protein. A typical dipstick can detect albumin levels above 300 mg/L, but levels between 30 - 300 mg/L are also clinically significant, defined as microalbuminuria. As such, a direct laboratory examination of the urine to exactly measure protein and albumin contents, usually as part of the albumin-creatinine-ratio (ACR), is more clinically useful than the urine dipstick test for protein.

A positive result shows albuminuria, which can be seen in many kidney disorders, but also to some degree in healthy people and during fever.

Glucose

The glomeruli usually reabsorb virtually all filtrated glucose, but if the serum glucose level rises above 10 mmol/L, the reabsorption cannot keep up, causing glucosuria. This is present in people with diabetes mellitus.

Ketones

Ketones are present in the urine when they're present in the blood, which occurs during ketoacidosis and starvation. Diagnosis of these conditions rarely depend on the urine analysis, as we usually diagnose ketoacidosis based on serum glucose levels anyway.

Haemoglobin

The urine dipstick can be helpful in diagnosing microscopic haematuria. This can be useful in the evaluation of urinary tract pathologies like stones and cancer. Urinary tract infection can also cause microhaematuria. In case of gross haematuria, the urinary dipstick result has no clinical utility.

pH

Some dipsticks may measure urine pH. It's normally 4 - 8. Acidic urine may be a response to respiratory acidosis and increase the risk for uric acid stone or cysteine stone. Alkaline urine may be due to UTIs caused by urease-producing bacteria (Proteus spp.). Measurement of pH doesn't add much clinical value.

Macrosopic evaluation

• Amount
  • 500 – 2500 mL/day = normal
  • 100 – 500 mL/day = oliguria
  • < 100 mL/day = anuria
• Colour
  • Colourless
    • Very dilute urine, overhydration
  • Yellow
    • Normal
  • Cloudy/turbid
    • Pyuria
    • Phosphaturia
    • Chyluria
  • Red
    • Haematuria
    • Haemoglobinuria/myoglobinuria
    • Phenolphthalein (previously used in laxatives)
  • Orange
    • Dehydration
    • Rifampin
  • Brown
    • Urobilinogen
    • Porphyria
  • Drugs like metronidazole, chloroquine, nitrofurantoin, amitriptyline, methyldopa, sulphasalazine, etc. can cause abnormal colour of urine

Urine microscopy

• Procedure
  • Centrifugation -> removal of supernatant -> add solution or some drops of supernatant -> add to slide -> 10x, 40x, 400x magnification
• Epithelial cells
  • Squamous cells -> contamination
  • Transitional cells -> urothelial malignancy
• Bacteria
  • Detection of bacteria on microscopy is not reliable -> culture must be performed
• Leukocytes
  • Pyuria if >5 WBCs per field of view at 400x
• RBCs
  • Haematuria if >3 RBCs per field of view at 400x
• Casts – tubule-shaped structures
  • WBC casts -> pyelonephritis
  • RBC casts -> glomerulonephritis
  • Epithelial casts -> acute tubular necrosis
• Crystals are of low clinical significance