Haematuria
Introduction
Haematuria is a common condition and one which must be taken seriously. While there are some spurious reasons for patients reporting blood in the urine (eating beetroot, dye ingestion), most patients reporting macroscopic haematuria will be correct. An exception may be in women after the menopause confusing vaginal bleeding with blood in the urine, but this is rare.
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.
This essay will discuss the basic investigation and causes of true haematuria. While macroscopic haematuria is usually regarded as more urgent a problem than microscopic, the need for speedy investigation will be influenced by the patient’s general condition.
The management of haematuria has been revolutionised by the
advent of flexible cystoscopy,
meaning that patients can be speedily assessed (and usually reassured) with a
local anaesthetic outpatient procedure. This is now an option in the
outpatients department at the
After a general physical examination (not forgetting blood pressure, the prostate in a male and the gynaecological organs in a female), the first investigation in a patient with reported haematuria is urinary examination. This must include microscopy for red and white blood cells and bacteria. The presence of any crystals, ova or parasites should be noted and culture of a mid stream specimen carried out. If schistosomiasis or tuberculosis are suspected a first void urine sample is usually requested. The level of protein in the urine must be assessed, but in heavy haematuria it may be difficult to be sure if light proteinuria is due to the haemoglobin present. If no red blood cells are found in the urine but haemoglobin is present the patient should be investigated for causes of haemoglobinuria.
Further investigation can be done either in the hospital or primary care environment, depending on the interests of the general practitioner and the speed of availability of tests. In any case a close liaison between primary care and specialist is essential: at King’s College Hospital we encourage telephone calls whether for referral or simply advice, and I am always happy to discuss individual patients.
All patients should have a full blood count with an erythrocyte sedimentation rate. Serum urea, creatinine and electrolytes should be measured, along with albumin, calcium and liver function tests if the patient is unwell or in renal failure. Coagulation studies are not routine.
Assuming microscopic amounts of blood are found, the presence or absence of proteinuria may guide initial investigation, since the combination of these favour a glomerular problem. In this event C reactive protein and 24 hour urine protein excretion will be informative, as may serum electrophoresis and autoantibodies. Ultrasound will show renal cortical thickness and density. In the majority of cases a renal biopsy with immunoglobulin histochemistry will be necessary to make a definitive diagnosis: the need for this will be balanced against the patient’s state of health and the perceived risks of the possible disease or procedure.
In cases of microscopic haematuria without proteinuria, and all macroscopic cases, a “surgical” investigation plan can be followed. This is based around the exclusion of malignant or stone disease, and centres on cystoscopy to directly inspect the bladder. Other imaging may be done either by intravenous urography or a combination of plain abdominopelvic radiography and ultrasound of the urinary tract.
An argument can now be made for the use of spiral computerised tomography, which while giving a slightly higher radiation doe compared to a standard IVU has a higher snestivity and specificity for many urinary lesions than other imaging methods. In the event of a renal lesion being suggested, computerised tomography will usually give a definitive diagnosis without the need for biopsy, although this may vary. In suspected ureteric lesions, further information can be gained by either retrograde contrast radiography or direct inspection via the ureteroscope.
If no abnormality is found then a flexible cystoscopy under local anaesthetic may be performed, but if either the imaging or this endoscopic examination suggest a bladder lesion the patient will require a transurethral biopsy and examination under anaesthetic for both treatment and diagnosis.
In any of the above scenarios it is important to remember
that if a particular investigation pathway leads to a negative result,
consideration should be given to carrying out the test of the other pathways,
thus flexible cystoscopy for a patient with persistent microscopic haematuria
in whom no renal cause is found, and ultrasound in a patient with a normal
bladder and intravenous urogram.
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.
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.
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 by radiological emobolisation or surgery, conserving normal renal tissue where possible.
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 although large or complex stones may need percutaneuous or open surgical removal.
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.
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.
This 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
Again, these nearly always present with pain but may have haematuria as the only symptom. The presence or absence of obstruction and the size of the stone dictates management.
Typically cystitis is painful and in men is commonly associated with bladder outflow obstruction. Schistosomiasis, interstitial cystitis and drug related cystitis are rarer causes of bladder inflammation causing bleeding. Diagnosis is by urine microscopy and culture, assisted by cystoscopy. Bladder biopsies may be necessary.
Most of the interest in painless haematuria stems from the desire to diagnose bladder tumours at an early stage. Nearly all are transitional cell cancers, with smoking and aromatic hydrocarbon exposure being risk factors. Rarer bladder tumours include adenocarcinoma (usually arising from the urachus) and squamous cancer (associated with chronic inflammation and schistosomiasis).
Diagnosis is as outlined above with management depending on the stage and grade: 70% are superficial at presentation and are managed by transurethral surgery with or without the use of intravesical therapy. For invasive tumours the choice lies between radical cystectomy or radiotherapy. Metastatic disease may respond to platinum based chemotherapy.
Benign prostatic hyperplasia is ubiquitous but can bleed on its own: it may also cause bacterial cystitis. Diagnosis is by urinary flow assessment and bladder residual volume measurement. Assuming that other causes of haematuria have been ruled out, treatment is tailored to the individual.
Prostate specific antigen levels should be checked (after any UTI has been treated) to rule out prostate cancer, which may cause haematuria directly or by urinary tract infection. Diagnosis is by prostatic biopsy, usually with ultrasound control. Treatment depends on the stage and outlook, but local disease may be suitable for radical prostatectomy or radiotherapy while advanced disease responds to hormonal manipulation.
Arteriovenous malformations, tuberculosis and arteritis may all cause haematuria. Patients on anticoagulants who have control in the normal therapeutic range and who have haematuria must be fully investigated as above, since haematuria is not a normal consequence of anticoagulation.