Hematuria refers to the presence of red blood cells in the urine, which is only found microscopically in mild cases and red in severe cases. Asymptomatic microscopic hematuria is about 2.5% to 20% in population-based surveys. Hematuria is also known as “blood in urine” and “blood in drowning” in Chinese medicine. It refers to a disease in which blood is mixed with urine or pure blood and there is no pain when urinating.
Generally speaking, 90% of hematuria is caused by infections, stones and malignant tumors of the urinary system. In adolescents, hematuria is commonly caused by urinary tract infections, stones and bladder tumors; in patients aged 40-60 years, bladder tumors, kidney or ureteral tumors are common in men, and urinary tract infections, stones and bladder tumors are common in women; in patients over 60 years, enlarged prostate, prostate cancer and urinary tract infections are common in men, and bladder tumors and urinary tract infections are common in women.
The causes of hematuria can be broadly classified as follows.
1.Urological diseases
Such as inflammation of the urinary tract, stones, tumors, diverticula, polyps, malformations or vascular abnormalities, trauma, etc.
2.Urinary tract adjacent organ disease
Such as prostatitis, acute appendicitis, acute pelvic inflammatory disease, rectal and colonic cancer, etc.
3.Systemic diseases
(1) Infections: such as infective endocarditis, sepsis, epidemic hemorrhagic fever, scarlet fever, leptospirosis, filariasis.
(2) Blood diseases: such as thrombocytopenic purpura, allergic purpura, leukemia, hemophilia.
(3) Connective tissue diseases: such as systemic lupus erythematosus, polyarteritis nodosa.
(4) Cardiovascular disease: such as acute hypertension, renal stasis, renal artery embolism, renal infarction.
(d) Drugs and chemical factors such as sulfonamides, anticoagulants, cyclophosphamide, mercury agents, mannitol, spotted vine, etc. side effects or toxic effects.
(v) Others Such as post-exercise hematuria.
Diagnosis and differential diagnosis
1.Diagnostic and differential diagnostic ideas
(1) Patients with carnal hematuria should first identify whether it is true hematuria. In female patients, blood in the urine may be caused by blood from outside the urinary tract, such as menstruation, vaginal bleeding, or hemorrhoid bleeding, etc. Therefore, attention should be paid to female patients to exclude “pseudohematuria” caused by this. The use or injection of certain drugs (such as rifampin, vitamin B2, etc.) or dyes (such as phenol red) can make the urine red; hemoglobinuria can be dark red or soy sauce colored; hematoporphyria and lead poisoning can also appear as red urine, but in the above cases, no red blood cells appear, so it is also “pseudohematuria”.
(2) For patients with true hematuria, we should first confirm whether the hematuria is caused by systemic hemorrhagic disease or damage to organs of the adjacent urinary system through medical history and laboratory tests. Such patients can often be found clinically with other clinical symptoms in addition to hematuria: systemic hemorrhagic diseases can manifest as bleeding from the skin and other organs, and blood tests often show abnormal findings; appendicitis, pelvic inflammatory disease, etc. all have specific sites of pain and other inflammatory manifestations, etc.
(3) After excluding hematuria caused by other systemic diseases, the source of hematuria should be localized within the urinary system. The initial hematuria often indicates bleeding from the anterior urethra, the complete hematuria indicates bleeding from the urinary tract above the bladder neck, and the terminal hematuria indicates bleeding from the base of the bladder, posterior urethra, prostate or seminal vesicles.
Clinically, complete carnal hematuria and microscopic hematuria are often divided into glomerular hematuria (aberrant or polymorphic red blood cells) and non-glomerular hematuria (normal or homogeneous red blood cells) by the fractionation of urinary red blood cell morphology. As the name implies, glomerular hematuria usually originates from within the glomerulus and is generally seen in glomerular diseases, mainly due to leakage of red blood cells caused by damage to the glomerular basement membrane; non-glomerular hematuria originates from other parts of the urinary tract below the glomerulus, generally due to local vascular bleeding caused by inflammation, stones, trauma, tumors, vascular malformations and other lesions in the renal pelvis, renal calyces, ureter, and bladder.
(4) After the localization of hematuria, further analysis of the etiology of hematuria should be performed. Glomerular hematuria can occur in glomerular diseases with manifestations of thylakoid proliferation, such as renal pathology manifesting as intracapillary proliferative nephritis, crescentic nephritis, thylakoid proliferative nephritis, IgA nephropathy, membranoproliferative nephritis, focal segmental glomerulosclerosis, and other lesions. In addition, glomerular hematuria can also be seen in those with significant changes in basement membrane structure, such as thin basement membrane nephropathy and hereditary nephritis. Since there is no good correlation between the severity of hematuria and proteinuria and the degree of renal disease, renal puncture biopsy is often required to determine the histological type of renal disease in these patients to provide a basis for treatment and prognosis. In patients who present with simple hematuria, it is currently believed that because most patients have mild lesions, renal pathology may not be performed, but close clinical follow-up is required.
In patients with non-glomerular hematuria, careful urinary system imaging should be performed, and cystoscopy can be performed if necessary to confirm or exclude inflammation, stones, tumors and vascular lesions of the urinary system.
2.Local diagnosis of hematuria
(1) Judgment of glomerular and non-glomerular hematuria
Tubular urine: If tubular type can be found, especially red blood cell tubular type is a characteristic of glomerular hematuria, but the number of red blood cell tubular type in urine sediment is not much, and it is easy to miss in ordinary microscopic examination, if it can be examined by bitonal microscopy, it is easier to observe the tubular type.
Urine protein measurement: hematuria with significant proteinuria is often glomerular hematuria. If the glomerular hematuria is hematuric to the naked eye and its urine protein is >1g/24h or qualitatively >++, it is indicative of glomerular disease. It must be noted, however, that some glomerular diseases may be without proteinuria and show only hematuria.
Urinary erythrocyte morphology: observation of urine sediment with a phase contrast microscope (PCM ) is the main method to determine glomerular hematuria, and the rate of aberrant red blood cells in renal hematuria is >80%. in 1982, Fairley applied phase contrast microscopy to examine urinary erythrocyte morphology to identify the source of hematuria.
Analysis of mean volume and distribution curve of urinary red blood cells: The mean volume and distribution curve of red blood cells in fresh urine specimens were determined by automatic hematocrit calculator, and if the mean volume was ≤72fl and the distribution curve showed small cell distribution, it indicated that the hematuria mostly originated from the glomerulus.
(2) Upper urinary tract and lower urinary tract bleeding
Upper urinary tract hemorrhage: mostly dark brown urine, no bladder irritation signs, sometimes worm-like blood clots can be seen; sometimes accompanied by renal colic; those with blood clots are usually not glomerular disorders, but ureteral or renal pelvis bleeding or renal tumor bleeding.
Lower urinary tract bleeding: The three-cup urine test is particularly helpful in diagnosing lower urinary tract bleeding. The patient is asked to urinate in 3 glasses without interruption, 10-15 ml in the first glass, 10-30 ml in the third glass and the rest in the second glass for visual and microscopic examination. If the 1st glass has increased cells (initial hematuria), it is bleeding from the anterior urethra; if the 3rd glass has increased red blood cells (terminal hematuria), it is mostly bleeding from the base of the bladder, prostate, posterior urethra or seminal vesicles; if all 3 glasses have different degrees of bleeding (whole hematuria), it is bleeding from the bladder neck and above.
3.The root disease diagnosis of hematuria
(1) Glomerular disease
If glomerular hematuria has been identified, further relevant screening tests should be performed to distinguish whether it is primary or secondary, such as checking serum antinuclear antibody, anti-double-stranded DNA antibody and complement to exclude lupus nephritis, etc., so as to finally clarify the underlying disease. Renal biopsy provides a histological diagnosis and is particularly valuable in the diagnosis of patients under 40 years of age with hematuria. With the improvement and accuracy of renal histomorphology, more so-called unexplained hematuria has been identified as glomerular disease.
(2) Non-glomerular disease
In the case of non-glomerular hematuria, the most common causes are kidney stones (26%) and infectious diseases of the urinary tract (24%), and only 2.2% to 12.5% of microscopic hematuria is eventually found to have a malignant tumor of the urinary tract. Targeted investigations, such as urine bacteriology in cases of lower urinary tract syndrome, should be performed according to the clinically suspicious presentation. For non-renal hematuria without specific symptoms, the examination steps are as follows.
Abdominal plain film 90% of kidney stones are radiopaque to X-rays, which is more helpful for diagnosis and also to understand the morphology, size and location of the kidney. A whole urinary tract plain film should be taken before IVP.
Intravenous pyelogram (IVP): IVP should be considered in any patient with hematuria who cannot be diagnosed with glomerulonephritis.
Renal ultrasonography: It is more accurate than IVP for diagnosing renal masses and cysts. The minimum limit of ultrasonographic detection of masses is 2.5 cm, and for polycystic kidneys, ultrasound is more accurate than renal body photographs and CT scans. Cysts can be detected at 1 cm in diameter. In skilled individuals, stones may be detected that are not detected by X-ray.
CT scan: This test is considered in those with normal IVP and ultrasound and can detect masses smaller than 2 cm. It can detect renal artery aneurysms and renal vein hemorrhage formation.
Cystoscopy: If the diagnosis is not clear with IVP and the patient is >40 years old with persistent hematuria, cystoscopy should be performed as soon as possible. Cystoscopy is particularly helpful in identifying the cause of lower urinary tract bleeding and in diagnosing unilateral renal and ureteral hematuria, the latter being detected only when the hematuria has not yet stopped.
Urine cytology: This test should be done when tumors of the bladder, urethra or renal pelvis are suspected, especially in elderly patients with hematuria.
4.Diagnosis of unexplained hematuria
Unexplained hematuria is a sign caused by various diseases, and its pathological anatomical causes can be: minor focal infection of the kidney; microscopic stones; small renal tumors; glomerular disorders; lesions of the renal vascular system; early polycystic kidney; hereditary hemorrhagic capillary dilatation; hematuria caused by causes other than the urinary system; allergic renal hemorrhage; use of nephrotoxic drugs such as sulfonamide and gentamicin; etc. Arterial embolism of the kidney secondary to cardiac disease.
Although the diagnostic techniques for hematuria have improved greatly in recent years and many of the previously unexplained hematuria have been diagnosed, there are still about 5% of patients with hematuria whose cause cannot be identified after various diagnostic techniques. These patients should be followed up regularly. Adolescents with unexplained hematuria should have their urine examined once a month. If microscopic hematuria persists or if urine protein is ≥500 mg/24h, it is likely to be glomerular disease. In contrast, those over 50 years of age should pay close attention to the possibility of tumor and should undergo routine urine and urine cytology every six months, IVP once or twice a year, and cystoscopy if necessary. If hematuria persists, follow-up should be done for more than 3 years. In some patients, the hematuria may disappear on its own, but it is still advisable to follow up for 1 year after the hematuria disappears.