User:Mohammad Aldalou/sandbox

Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. It can be classified according to the quantity, the anatomical origin of bleeding and the occurrence during bleeding.


 * As per the quantity, hematuria can be detected by the naked eye (gross hematuria), or can only be detected under microscopy (microscopic hematuria)
 * As per the anatomical origin, blood or red blood cells can enter and mix with urine at multiple anatomical sites, these include the urinary system, female reproductive system, and integumentary system. Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus. These can be divided into glomerular and non-glomerular causes. Non-glomerular causes can be further subdivided into upper urinary tract and lower urinary tract causes.
 * As per the occurrence during bleeding, hematuria can be initial, terminal or total.

When hematuria is detected, conducting a thorough history, physical examination and further evaluation (e.g; imagining, cystoscopy) of the urinary tract helps determining the underlying cause and stratifying patients into high and low risk. High-risk patients include those with visible hematuria or those with non-visible hematuria and risk factors.

Differential diagnosis
Urinary causes occur anywhere between the kidney glomerulus and the urethral meatus. These can be divided into glomerular and non-glomerular causes. In general, nephrologists are the experts of glomerular hematuria while urologists manage non-glomerular hematuria. The differential diagnosis can be furthered refined by the temporality of hematuria and associated symptoms. Microscopic hematuria has a prevalence of 2% to 31%, depending upon age, sex, and other factors.

Glomerular hematuria
A glomerular etiology is suggested by brown colored urine, red blood cells casts, dysmorphic red blood cells, protein. This requires the consultation of a nephrologist. Common causes include:

==== 1- Nephritic Syndrome ====


 * IgA nephropathy
 * Thin glomerular basement membrane disease
 * Hereditary nephritis (Alport's disease)
 * Hemolytic uremic syndrome
 * Postinfectious glomerulonephritis
 * Membranoproliferative glomerulonephritis
 * Lupus nephritis
 * Henoch-Shonlein purpura

==== 2- Isolated Hematuria ====


 * Transient: Infections, Exercise
 * Persistent: Mostly Alport Syndrome

==== 3- Idiopathic hematuria is considered a glomerular syndrome. ====

=== Non-glomerular hematuria === A non glomerular etiology is suggested by reddish pink urine, eumorhpic red blood cells, and passage of blood clots.


 * Infections: Pyelonephritis, Cystitis, Prostatitis, Urethritis.
 * Urolithiasis: Renal Stones, Ureteral Stones, Bladder Stones
 * Malignancy: Renal Cell Carcinoma, Urothelial Cancer, Prostate Cancer.
 * Urinary Tract Obstruction: Urethral Strictures, Prostate hyperplasia, Congenital anomalies.
 * Renal Papillary Necrosis: Sickle Cell Disease, Diabetes mellitus.
 * Polycystic kidney disease
 * Coagulation Disorders: Platelet dysfunction, Hemophilia
 * Trauma: renal, ureteral, bladder, urethral injuries.
 * Drugs: Warfarin, Heparin, NSAIDs, Cyclophosphamide.

Hemoglobinuria
It's the presence of hemoglobin in urine, causing red-cocacola discoloration. Common cause of hemoglobinuria :


 * Intravascular hemolysis : Hemolysis is a process where red blood cells lyse or burst. This releases hemoglobin into the bloodstream. Hemoglobin then leaves the bloodstream and enters urinary tract at Bowman's capsule.

Myoglobinuria
It's the presence of myoglobin in urine, causing red-cocacola discoloration. Common cause of myoglobinuria :


 * Rhabdomyolysis: extensive muscle injury causing skeletal muscle tissue breakdown. This releases myoglobin into the bloodstream, which leaves it later entering the urinary tract.

Hematuria in children
Common causes of hematuria in children are:


 * Fever
 * Strenous Excercise
 * Acute nephritis
 * Congenital abnormalities:
 * Non-vascular: ureteropelvic junction obstruction, posterior urethral valves, urethral prolapse, urethral diverticula, multicystic dysplastic kidney
 * Vascular: arteriovenous malformations, hereditary hemorrhagic telangiectasias, renal vascular thromboses.
 * Urinary stones.
 * Coagulation disorders.
 * Mechanical trauma: masturbation, foreign body.
 * Nephritic Syndrome: IgA nephropathy, Post-streptococcal glomerulonephritis, Benign familial hematuria, Alport syndrome.
 * Sickle cell trait or disease.

Pathophyisiology
Common mechanisms are:


 * Structural disruption in the integrity of the glomerular basement membrane.
 * Disruption of the renal tubules.
 * Mechanical erosion of the mucosal surfaces of the genitourinary tract.

Diagnosis
After conducting a thorough history and physical examination, further medical investigations are determined, this includes laboratory tests, imaging studies or even cystoscopy.

History and examination
The differential diagnosis can be furthered refined by detailed history, it helps distinguish the potential underlying causes. Main points to consider:


 * The occurrence of hematuria during urination: blood can appear in the urine at the onset, midstream, or later. If it appears soon after the onset of urination, a distal site is suggested. A longer delay suggests a more proximal lesion. In other words, shorter times suggest distal sites while longer times suggest proximal sites. Hematuria that occurs throughout urination suggests that bleeding is occurring above the level of the bladder.
 * Associated signs and symptoms:


 * 1) Fever, abdominal pain, dysuria, frequency suggest urinary tract infection.
 * 2) Periorbital puffiness, decreased urine output, dark-colored urine, edema or hypertension suggest a glomerular cause.
 * 3) Costovertebral angle tenderness suggests upper urinary tract obstruction. A urinary stone is suggested by the presence of renal colic.
 * 4) Passage of visible clots suggest an extraglomerular cause.
 * 5) Joint pains, skin rashes, and prolonged fever suggest collagen vascular disorder, espically in adloscent.
 * 6) Hematuria alone without accompanying symptoms should be raise suspesion of malignancy of the urinary tract until proven otherwise.


 * Recent history: can be suggestive of trauma, infection or substance intoxication.
 * Family history: can be suggestive of Alport disease or polycystic kidney disease.

Labratory tests
Ordered labratory tests must be based on the history and clinical examination findings. Main tests:


 * Urine dipstick: one of the most useful and sensitive tools in detecting hematuria, but with low specifity as it also give positive results when myglobinurea and hemoglobinurea are present.
 * Urine sidement : confirms hematuria under microscopy, more than 3 RBCs per high power field is generally considered abnormal.
 * Urine culture: peroformed in case urinary tract infection is suspected, it distinguishes the causative organism.
 * Electorlytes, serum creatinine, and blood urea nitrogen levels; performed
 * Coagulation studies; performed in case coagulopathy or drug intoxication are suspected.

Imaging studies

 * Renal and bladder ultrasonography: it's indicated in case of macroscopic hematuria in absecne of any other finding as proteinuria or red blood cells casts.
 * Multi-phasic computed topography (CT) urography: it's the preferred modality, it is a three-phase study that includes a non-contrast phase, an arterial phase, and an excretory phase. The study should sufficiently evaluate the kidney and the urothelium lining the upper urinary tracts.
 * Voiding cystourethrography: it's effiecent in detecting urethral and bladder abnormalities, and determine urine reflux.
 * Radionuclide studies: it's efficent in evaluating obstructive caliculi, and detecting renal scars.

Cystoscopy
It's indicated if malignancy (urothelial papilloma) is suspected. Mainly performed in case of young patients (>35 years old) presenting with asymptomatic microscopic hematuria, in the presence of other risk factors.

Kidney Biopsy
It's performed rarely and only in specific relative indications as follows:


 * Significant proteinuria
 * Abnormal renal function
 * Recurrent persistent hematuria
 * Abnormal serological findings
 * Family history of end-stage renal disease

Follow up
Evaluations of hematuria that do not reveal pathology require follow up. A urinary cytology may be helpful. A urinalysis should be repeated once a year. Follow up can be discontinued after two consecutive negative urinalyses. Repeat hematuria on follow-up studies warrants repeat upper urinary tract imaging and a cystoscopy. This should be performed within three to five years of the first evaluation.

Management
Asymptomatic hematuria does not require treatment in most cases. In case there is a signficant clinical, lab or imaging finding, treatment is indicated according to the underlying casue.

Surgery
Surgical intevention may be indicated in certain anatomic abnormalities, such as ureteropelvic junction obstruction, tumor, or significant urolithiasis.

Medical emergency: acute clot retention
Acute clot retention is one of three emergencies that can occur with hematuria. The other two are anemia and shock. Blood clots can prevent urine outflow through either ureter or the bladder. This is known as acute urinary retention.

Blood clots that remain in the bladder are digested by urinary urokinase producing fibrin fragments. These fibrin fragments are natural anticoagulants and promote ongoing bleeding from the urinary tract. Removing all blood clots prevents the formation of this natural anticoagulant. This in turns facilitates the cessation of bleeding from the urinary tract.

The acute management of obstructing clots is the placement of a large (22-24 French) urethral Foley catheter. Clots are evacuated with a Toomey syringe and saline irrigation. If this does not control the bleeding, management should escalate to continuous bladder irrigation (CBI) via a three-port urethral catheter. If both a large urethral Foley catheter and CBI fail, an urgent cystoscopy in the operating room will be necessary. Lastly, a transfusion and/or a correction of a coexisting coagulopathy may be necessary.

Epidemiology
In the United States of America, microscopic hematuria has a prevalence of somewhere between 2% and 31%. Higher rates exist in individuals older than 60 years of age and those with a current or past history of smoking. Only a fraction of individuals with microhematuria are diagnosed with a urologic cancer. When asymptomatic populations are screened with dipstick and/or microscopy medical testing about 2% to 3% of those with hematuria have a urologic malignancy. Routine screening is not recommended. Individuals with risk factors who undergo repeated testing have higher rates of urologic malignancies. These risks factors include age (>35 years), male gender, previous or current smoking, chemical exposure (e.g., benzenes or aromatic amines), and prior pelvic radiation therapy.

Racial, sex and age related demographics
Incidenence of hematuria in a specific racial group is determined by the incidence of the underlying disease. For example, hematuria caused by sickle cell disease is more common in blacks and hispnics than whites. Incidence of hematuria in a sex group is also determined by the incidenece of the underlying disease. For example, hematuria caused by lupus nephritis is more common in adolscent girls. Prevalnce of hematuria of certain conditions varies with age. For example, hematuria caused by wilms tumor is more common in pre-school children, while hematuria caused by malignancy is more common in adults.

Children
In pediatric populations, the prevalence is 0.5–2%. Risks factor include older age and female gender. About 5% of individuals with microscopic hematuria receive a cancer diagnosis. 40% of individuals with macroscopic hematuria (blood easily visible in the urine) receive a cancer diagnosis.