What is haematuria?

Haematuria is the presence of red blood cells in the urine. It can range from obvious bleeding to the microscopic detection of a few red blood cells in a routine urine sample.

When the urine is visibly coloured red by the amount of blood present it is called macroscopic haematuria. Blood that is not visible to the naked eye, but that is apparent on microscopic examination or with a urine test strip is called microscopic haematuria.

Unfortunately there is a poor correlation between the degree of haematuria and the severity of any underlying cause. An older person with visible haematuria is more likely to have serious underlying pathology than a younger person with microscopic haematuria and no symptoms. All people with haematuria need further investigation.

Causes of haematuria

Blood in the urine can come from anywhere in the urinary tract: from the kidneys at the top down to the urethra (tube that carries urine from the bladder to the exterior).

There is a very long list of possible causes, but infections, stones, tumours or trauma (injury) account for the majority of cases.

In a person over 40 years of age with painless macroscopic haematuria, the most important cause to exclude is bladder cancer. Three main types of cancer occur in the bladder. The lining of the bladder, the ureter and the drainage system of the kidney consist of transitional cells. The most commonly found cancer is called transitional cell carcinoma. Cancers are usually named after the cells from which they originate.

The two other types of cancer found in the bladder are called squamous carcinoma and adenocarcinoma. Squamous carcinoma classically occurs after many years of bladder irritation as is seen with chronic bilharzia.

Adenocarcinoma of the bladder is rare. Its name is derived from the fact that the cancer contains gland-like elements.

Possible causes of bleeding from the upper urinary tract

Kidney

• Trauma

   

  • Blunt
  • Penetrating
     
• Kidney stones, Stone disease is very common, with concretions forming in the renal papillae, which then form a nidus for stone formation in the collecting system. While most stones may cause infection, one particular type (infection or matrix stone) is thought to be caused by bacteria that are able to split urea to form ammonium. Renal stones tend to be asymptomatic but may cause haematuria by either infection or direct irritation of the mucosa. They may also cause renal pain if large enough or obstructing. Diagnosis is by imaging, usually intravenous urography. Renal stones can usually be treated by extracorporeal shock wave lithotripsy on an outpatient basis, although large or complex stones may need percutaneous or open surgical removal.
  
   
• Tumours
  • Carcinoma of renal parenchyma ("meat" of the kidney)
     
  • Benign renal tumours may cause both bleeding and diagnostic difficulty. They are, with the exception of the incidental and usually asymptomatic renal cyst, rare. Angiomyolipoma is a hamartomatous lesion, which may grow to great size and be associated with major haemorrhage; treatment is again surgical, conserving normal renal tissue where possible
     
  • Transitional cell carcinoma of the renal pelvis (cancer of the lining of drainage system of the kidney, see above) Transitional Cell carcinoma of the renal collecting system usually gives haematuria.
  • 
  • Diagnosis may be difficult, requiring retrograde imaging and ureteroscopy. Treatment is by either local excision or, for high grade or larger lesions, nephro-ureterectomy. Immunotherapy is used for metastases with limited success; radiotherapy has little place except for palliation of bone metastases
    .
•  
  • Angiomyolipoma
     
  • (a benign tumour of the kidney containing large numbers of blood vessels and fat, prone to spontaneous bleeding) The commonest primary renal tumour is renal cell carcinoma, an adenocarcinoma of collecting tubule origin. It commonly presents with haematuria although most are nowadays picked up incidentally by ultrasound scanning. Diagnosis is made by CT scanning and treatment is by surgical excision. Small tumours may now be treated by local excision with preservation of kidney function.
    
     
• Infections
  • Tuberculosis
  • Pyogenic infections - which are infections caused by pus forming bacteria
     
• Congenital (born with) disorders
  • Polycystic kidney disease
  • Renal cysts
    
    
    
     
• Bleeding disorders
  • Haemophilia
  • Leukemia
  • Sickle cell disease
  • Anticoagulant therapy such as warfarin
     
• Vascular causes
  • Renal emboli (blood clots)
  • Renal vein thrombosis
     
• Interstitial renal disease
  • Glomerulonephritis Glomerulonephritis tends to present with microscopic haematuria. While pain may be associated, most cases will have either no symptoms or may show signs of renal failure. Investigation is as outlined above.
    
    Pyelonephritis (ascending urinary tract infection)
    Acute bacterial pyelonephritis results from bacteria ascending from the bladder either by direct spread (vesico-ureteric reflux) or possibly by periureteric lymphatic extension. Painless haematuria may occur but the symptom complex usually includes loin pain, fever and possibly septicaemia.
     
  • IgA Nephropathy
  •  
  • Papillary NecrosisThis condition occurs in diabetics and in patients with deficiencies of oxygenation, particularly sickle cell disease. It is characterised by a radiolucent filling defect on IVU and may usually be treated expectantly

     

Ureter (drainage tube of the kidney)

• Trauma (rare in isolation)
• Infection
• Ureteric stones
• Ureteric tumours (rare)
  • Transitional cell carcinoma (cancer of the lining of the ureter, see above)

Possible causes of bleeding from the lower urinary tract

Bladder

• Trauma
  
• Infections
  • Haemorrhagic cystitis (severe cystitis associated with bleeding from the bladder)
  • Tuberculosis
  • Schistosomiasis (Bilharzia)
     
• Stone disease is very common
  , with concretions forming in the renal papillae, which then form a nidus for stone formation in the collecting system. While most stones may cause infection, one particular type (infection or matrix stone) is thought to be caused by bacteria that are able to split urea to form ammonium. Renal stones tend to be asymptomatic but may cause haematuria by either infection or direct irritation of the mucosa. They may also cause renal pain if large enough or obstructing. Diagnosis is by imaging, usually intravenous urography. Renal stones can usually be treated by extracorporeal shock wave lithotripsy on an outpatient basis, although large or complex stones may need percutaneous or open surgical removal
   
• Transitional cell carcinoma (see above)
• Squamous cell carcinoma (see above)
• Adenocarcinoma (see above)
  
  
   

• Radiation
• Exercise induced haematuria (long distance running can cause the layers of the empty bladder to rub on each other, thereby causing bleeding)
• Drugs
  • Cyclophosphamide - a drug used in the treatment of cancer

Prostate

Urethra

• Trauma
• Urethral tumours (very rare)
• Urethritis - infection of the urethra

When is red urine not haematuria?

The most common cause of a false positive finding of haematuria is contamination of the urine sample with menstrual blood.

Certain food dyes and beetroot can also render the urine red.

Several drugs such as pyridium (for pain relief of the urinary tract) and the anti-tuberculosis drug rifampacin change the colour of the urine to orange and can be confused with haematuria.

Haemoglobin, a breakdown product of red blood cells, will test positive on a urine test strip but will not be seen as red blood cells under the microscope. This means that the presence of heamoglobin in the urine will give a false positive test for blood.

How is haematuria diagnosed?

• Urine test strip (dipstix)
• Urine microscopy

Haematuria is usually divided into macroscopic (where the urine is discoloured) and microscopic (where the blood is found only on dipstick or microscopy examination). Further clinically relevant distinctions can be made between painful and painless haematuria, and haematuria of glomerular and post-glomerular origin
Macroscopic haematuria may be very obvious with clearly visible blood or clots in the urine.

Microscopic haematuria can be detected using urine test strips (dipstix) or urine microscopy. Urine test strips are very sensitive to the presence blood in the urine, but the findings should be confirmed with microscopic examination.

The test strips react with haemoglobin from within the red blood cells. Haemoglobin within the urine can lead to false positive tests. False negative test strip analysis is very rare.

How is the cause of haematuria identified?

• History
• Physical examination
• Urine analysis
  • Microscopy and culture
  • Cytology - looking at cells under the microscope
• Imaging
  • Intravenous pyelogram
  • Ultrasound
  • CT scanning
• Cystoscopy

A good clinical history and a thorough physical examination will often, but not always, indicate the likely source of bleeding.

A history of significant trauma is usually quite apparent. Blood that is seen only at the beginning of the stream is called initial haematuria and is characteristic of a urethral source. The passage of clear urine with blood and pain right at the end of the stream is called terminal haematuria, and is a classic sign of Bilharzia or a bladder stone. The stone causes pain and bleeding as the bladder empties around it. When all of the urine is discoloured by blood it is called total haematuria. In total haematuria the source can be anywhere in the urinary tract.

Loin or flank (side) pain associated with haematuria may indicate kidney pathology such as a stone, infection or a tumour. Bladder infections (cystitis) can bleed heavily. Patients with bleeding due to cystitis usually have the associated symptoms of bladder pain and burning with passing urine. Painless macroscopic haematuria in a middle-aged patient is most likely due to bladder cancer. In males the symptoms of bladder outflow obstruction such as a poor stream, hesitancy and straining with passing urine may indicate prostatic problems.

The physical examination of a patient with haematuria should be thorough and should include a rectal examination in a male and a vaginal examination in a female. The physical examination may detect a palpable mass in the kidney or an enlarged prostate gland.

The presence of blood in the urine should be confirmed on microscopy. The urine sample is cultured to rule out or prove infection as a cause. Urine cytology is a test that looks at the characteristics of cells found within the urine. It is useful in the follow-up of cases of known previous bladder cancer, where its main role is in the detection of tumour recurrence. Urine cytology is not usually used in the initial investigation of patients with haematuria.

An ultrasound scan combined with an ordinary abdominal X-ray is a viable alternative to IVP. The advantages of ultrasound are that it does not involve any radiation or contrast medium and that it is non-invasive. Ultrasound is also more sensitive than IVP in the detection of small tumours of the renal parenchyma. Ultrasound is less sensitive than IVP in the detection of small tumours of the drainage system of the kidney, however, and the accuracy of ultrasound is dependent on the skill of the person performing the procedure.

Ultrasound and IVP should be seen as complementary rather than mutually exclusive. In some patients it may be necessary to perform both tests in order to make an accurate diagnosis. If ultrasound or IVP suggests a mass in the kidney, then a CT scan is usually performed to define the mass in more detail. CT scanning is not usually used as a first-line investigation in haematuria.

An ultrasound scan or intravenous pyelogram (IVP) cannot rule out the presence of a bladder tumour. All patients with haematuria should undergo cystoscopy. Cystoscopy is the inspection of the inside of the urethra and bladder with a special instrument (cystoscope). The cystoscope is passed through the urethra into the bladder. The procedure can usually be performed under local anaesthetic as a day case.

If an abnormality such as a suspected bladder tumour is seen, a biopsy can be taken at the same time. A small biopsy can sometimes be taken under local anaesthetic but extensive biopsies are usually performed under spinal or general anaesthetic.