Hematuria copy

بسم الله الرحمن بسم الله الرحمن الرحيمالرحيم

HEMATURIAHEMATURIADr.Samir Sally,MD

Prof. internal medicine & nephrologyMansoura Urology & Nephrology Centre,

Mansoura University

CASECASE An otherwise healthy 48-year-old woman is

found to have microscopic hematuria (5 red cells per high-power field) on a urinalysis performed by a life insurance company. No other laboratory abnormalities are identified; the serum creatinine concentration is 0.8 mg per deciliter (70.7 µmol per liter). The woman reports no symptoms and is a nonsmoker. Her blood pressure is 118/74 mm Hg, and the findings on physical examination are normal. How should she be evaluated?

DEFINITIONDEFINITION

More than three red blood cells are found in centrifuged urine per high-power field microscopy( > 3 RBC/HP).

Normal urine:no red blood cell or less than three red blood cell

DefinitionDefinition

Macroscopic (gross) Hematuria

Visible (Red Urine)

Microscopic Hematuria

>3RBC/HPF from two of three urinary sediments without a urinary tract infection, or menstruation on microscopic evaluation

EvaluationEvaluationof the patient of the patient with with

HematuHematuriaria

29/1/2014

It is difficult to localize the site of bleeding by routine examination of the patient with hematuria.

However, certain findings may be very helpful depend on size & shape of RBCs.

For example, casts form in the lumina of renal tubules. Therefore, the presence of RBCs casts localizes the site of bleeding to the renal parenchyma.

HematuriaHematuria

Painful or painlessGross or microscopicInitial, terminal or totalTransient or persistentGlomerular or non glomerularPresence of clotsAzospermiafalse

ETIOLOGYETIOLOGY Diseases of the urinary system—the most

common cause Vascular arteriovenous malformation arterial emboli or thrombosis arteriovenous fistular nutcracker syndrome renal vein thrombosis loin-pain hematuria syndrom cogulation abnormality excessive anticogulation

Nutcracker syndromeNutcracker syndrome

Glomerular IgA nehropathy thin basement membrane disease (incl.Alport syndrome) other causes of primary and secondary glomerulonephritis

Interstitial allergic interstitial nephritis analgesic nephropathy renal cystic diseases acute pyelonephritis tuberculosis renal allograft rejection

Uroepithelium malignancy vigorous excise trauma papillary necrosis cystitis/urethritis/prostatitis(usually caused by infection) parasitic diseases (e.g. schistosomiasis) nephrolithiasis or bladder calculi

Multiple sites or source unknown hypercalciuria hyperuricosuria

System disorders a. Hematological disorders aplastic anemia leukemia allergic purpura hemophilia ITP (idiopathy thrombocytopenic purpura)

b. Infection infective endocarditis septicemia epidemic hemorrhagic fever ， Hantaan virus) scarlet fever (-hemolytic streptococcus) leptospirosis (leptospire) filariasis (Wuchereria bancrofti, Brugia malayi)

c. Connective tissue diseases systemic lupus erythematosus (SLE, polyarteritis nodosa

d. Cariovascular diseases hypertensive nephropathy chronic heart failure renal artery sclerosis

e. Endocrine and metabolism diseases gout diabetes mellitus

Diseases of adjacent organs to urinary tract appendicitis salpingitis carcinoma of the rectum carcinoma of the colon uterocervical cancer

Drug and chemical agents sulfanilamides anticoagulation cyclophosphamide （ CTX ） mannitol

miscellaneous exercise “idopathic” hematuria

Accompanied symptomsAccompanied symptoms

Hematuria with renal colic renal stone, ureter stone

if with dysuria or straining to void: bladder or urethra stone

Hematuria with urinary frequency,urgency and dysuria

bladder or lower urinary tract (tuberculosis or tumor)

if accompanied by high spiking fever, chill and loin pain: pyelonephritis

Hematuria with edema and hypertension glomerulonephritis hypertensive nephropathy Hematuria with mass in the kidney neoplasm hereditary polycystic kidney Hematuria with hemorrhage in skin and mucosa hematological disorders infectious diseases Hematuria with chyluria filariasisCyclic hematuria in women that is most prominent

during and shortly after menstruation, suggesting endometriosis of the urinary tract

Important areas to check on the physical examination

•Blood Pressure •Check for edema, especially around the eyes •Careful inspection of the external genitalia •Look for any rashes, evidence of trauma and bruising, petechiae •Exam all joints for signs of arthritis-red, warm, or swollen •Feel the abdomen carefully for any masses or tenderness. Check for CVA tenderness. Try to feel for enlarged kidneys. •Check for evidence of paleness or jaundice •Accurately measure length and weight and plot on growth chart.

LABORATORY TESTSLABORATORY TESTS

Three-glass testMethod: collecting the three stages of urine of a patient during micturitionResult: the initial specimen containing RBC—the urethra the last specimen containing RBC—the bladder neck and trianglar area, posturethra all the specimens containing RBC—upper urinary tract, bladder

NEJM, 2003

Evaluation of microscopic hematuria

--Approaching to the patient– (Harrison’s Principle of Internal

Medicine,14th Ed)HEMATURIA

proteinuria (>500mg/24h)Dysmorphic RBC or RBC casts

Pyuria,WBC casts urine culture eosinophils serologic and hematologic

evaluation: blood culture, anti-GBM Ab, ANCA, complement, cryoglobulin HBV,HCV,VDRL,HIV, ASLO

renal biopsy

Hb electrophoresis, urine cytology, UA of family member, 24h urinary calcium/uric acid

IVP+/-renal ultrasound

As indicated: retrograde pyelography or arteriogram of cyst aspiration

cystoscopy

CT scanbiopsy

open renal biopsyfollow

(-)

(-)

(-)

(-)

(-)(-)

(+)(+)

(+)

(+)(+) ANCA:antineutrophil cytoplasmic

antibody, VDRL:venereal dis. research laboratory, ASLO: antisteptolysin O, IVP: intravenous pyelography

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS

Polluted urine: menstruation Drug and food: phenosulfonphtha lein (PSP),uric

acid, vegetable Porphyrism: porphyrin in urine (+) Hemoglobinuria

hemolysis

occult blood test (+)

MyoglobinuriaMyoglobinuria

HEMOGLOBINURIAHEMOGLOBINURIA

RBC abnormality Defects of RBC membrane structure and function

(hereditary spherocytosis) Deficiency of enzymes (favism) Hemoglobinopathy (thalassemia) PNH

Phase-contrast microscopy

to distinguish glomerular from post glomerular bleeding

• post glomerular bleeding: normal size and shape of RBC

• glomerular bleeding: dysmorphic RBC (acanthocyte)

EXAMPLE OF PHASE-CONTRAST EXAMPLE OF PHASE-CONTRAST MICROSCOPY TEST MICROSCOPY TEST (glomerlar)(glomerlar)

EXAMPLE OF PHASE-CONTRAST EXAMPLE OF PHASE-CONTRAST MICROSCOPY TEST MICROSCOPY TEST (non-glomerlar)(non-glomerlar)

Glomerular HematuriaGlomerular Hematuria

RENAL

IgA nephropathy Alport syndrome Thin glomerular BM disease Post infectious MPGN

MULTI-SYSTEM

SLE nephritis HSP nephritis Wegener syndrome Goodpasture syndrome HUS Sickle cell Disease

Extraglomerular HematuriaExtraglomerular Hematuria

UPPER URINARY TRACT

pyelonephritis ATN papillary necrosis nephrocalcinosis thrombosis malformation SCD tumor PCKD

LOWER URINARY TRACT

cystitis urethritis urolithiasis trauma coagulopathy heavy excersise UPJ obstruction ureterocele

Urine CytologyUrine Cytology

The sensitivity of urine cytology for the diagnosis of urothelial cell cancer is low, and a negative result does not exclude patients from further testing.

It has been shown in multiple studies that the addition of urine cytology in the primary analysis of hematuria does not contribute to diagnosis which is usually made by cystoscopy or imaging.

Urine CultureUrine Culture

The addition of cultures of urine may be indicated if the sediment shows leukocytes.

Clinical Chemistry Clinical Chemistry

Important to support a nephrologic diagnosis

RFT Coagulation profile

ImmunologyImmunology

Antinuclear antibody (ANA) , Anti-double stranded (ds) antibody

C3 & C4 complement concentrations– Low in SLE, acute post infectious

glomerulonephritis, Cryoglobulinemia

ASO titre– High after streptococcal infection

SerologySerology

Hepatitis B and C, HIV serology

ANCA test for diagnosis of vascuilitis

Anti-GBM antibodies in GP syndrome C-ANCA P-ANCA

CystoscopyCystoscopy

The American Urological Association best practice policy suggests that, in patients at low risk for urothelial cancer, cystoscopy may be avoided.

Imaging of the bladder should preferably precede cystoscopy, so it can aid the urologist and improve diagnostic yield.

Investigation : Investigation : Radiology Radiology

Helical CT Urogram (preferredpreferred) Renal US

– Defines anatomy– Signs of glomerular disease , hydronephrosis, and

renal cysts– CT Urogram is usually preferred over US

Intravenous Pyelogram– Suspected Nephrolithiasis

Cystoscopy– Extraglomerular source of Hematuria

MRI Urography– Indicated where CT Urogram is contraindicated

(e.g. Pregnancy, Children)– Identifies urothelial cancer, Nephrolithiasis and

renal tumors

http://www.ajronline.org/doi/full/10.2214/AJR.10.4198

American Journal of Roentgenology. 2010

Abdominal RadiographsAbdominal Radiographs

Its overall sensitivity for renal and ureteral stones is only 45–60% in multiple studies

Non-contrast CTNon-contrast CT

It is now the reference standard for stone detection, and even very-low-dose unenhanced CT techniques with a radiation dose comparable to that of abdominal radiographs have shown better results

ADPKDADPKD

UltrasoundUltrasound

Ultrasound is suitable as first-line diagnostic test

In comparison with excretory urography, ultrasound showed a higher sensitivity for bladder tumors and equal (i.e., moderate) sensitivity for upper urinary tract tumors. Ultrasound alone is not sensitive (19–32%) for stone detection,

ADPKDADPKD

Excretory UrographyExcretory Urography

For hematuria, multiple studies have now shown the superiority of CT urography over excretory urography.

There is also a low sensitivity (< 60%) for renal tumors smaller than 3 cm for excretory urography

A : IVPB: (CT)C: CT urography

MR Urography (MRU)MR Urography (MRU) MRU has inherent advantages

in that it does not require ionizing radiation, has a high contrast resolution, has good sensitivity for contrast media, and has the possibility for better tissue characterization than other imaging techniques do

MR Urography (MRU)MR Urography (MRU)

However, MRU is costly, technically demanding, and not widely practiced.

Therefore, MRU expertise is available only in specific dedicated centers.

It is good for pediatric diseases and for the evaluation of obstructive disease.

Nephrological referral Nephrological referral ++ biopsy biopsy

Evidence of declining GFR (by >10ml/min at any stage within the previous 5 years or by >5ml/min within the last 1 year)

Stage 4 or 5 CKD (eGFR <30ml/min)

Significant proteinuria

Isolated hematuria with hypertension in those aged <40

Visible haematuria coinciding with intercurrent (usually upper respiratory tract) infection

Exercise induced hematuriaExercise induced hematuria

•Gross or microscopic hematuria that occurs after strenuous exercise and resolves with rest

•Direct trauma to the kidneys and/or bladder may be responsible for the hematuria

•Renal ischemia due to shunting of blood to exercising muscles

•Exercise-induced gross hematuria should be differentiated from two other potential causes of red to brown urine following exercise: myoglobinuria due to rhabdomyolysis; and march hemoglobinuria

•Evaluation is not warranted in patients under age fifty who are not at increased risk for bladder or kidney cancer

•Evaluation for other causes of hematuria is warranted if the hematuria persists well beyond one week

Henoch–Schönlein purpuraHenoch–Schönlein purpura

HSP is a systemic vasculitis (inflammation of blood vessels) and is characterized by deposition of immune complexes containing the antibody IgA.

Rash, arthritis, abdominal pain and hematuria

C/P of poststrept GNC/P of poststrept GN In general, the latent period is 1-2 weeks after a throat

infection and 3-6 weeks after a skin infection.

Dark urine (brown-, tea-, or cola-colored)This is often the first clinical symptom.

Dark urine is caused by hemolysis of red blood cells that have penetrated the glomerular basement membrane and have passed into the tubular system.

C/P of poststrept GNC/P of poststrept GN The onset of puffiness of the face or eyelids is sudden. It

is usually prominent upon awakening and, if the patient is active, tends to subside at the end of the day

In some cases, generalized edema and other features of circulatory congestion, such as dyspnea, may be present.

Edema is a result of a defect in renal excretion of salt and water.

Gross hematuriaGross hematuria Gross hematuria is suspected because of the

presence of red or brown urine. The color change does not necessarily reflect the

degree of blood loss, since as little as 1 mL of blood per liter of urine can induce a visible color change.

Gross hematuria with passage of clots almost always indicates a lower urinary tract source.

The initial step initial step in the evaluation of patients with red urine is centrifugation of the specimen to see if the red or brown color is in the urine sediment or the urine supernatant. 

Causes of Asymptomatic Causes of Asymptomatic Gross Hematuria by Gross Hematuria by

IncidenceIncidence Acute Cystitis (23%)Acute Cystitis (23%) Bladder Cancer (17%) Benign Prostatic Hyperplasia (12%) Nephrolithiasis (10%) Benign essential Hematuria (10%) Prostatitis (9%) Renal cancer (6%) Pyelonephritis (4%) Prostate Cancer (3%) Urethral stricture (2%)

The most common risk The most common risk factors for urinary tract factors for urinary tract

malignancy in AMH patientsmalignancy in AMH patients Age >35 years Smoking history in which the risk correlates with the

extent of exposure Occupational exposure to chemicals or dyes (benzenes

or aromatic amines), such as printers, painters, chemical plant workers

History of gross hematuria History of chronic cystitis or irritative voiding

symptoms History of pelvic irradiation History of exposure to cyclophosphamide History of a chronic indwelling foreign body History of analgesic abuse, which is also associated

with an increased incidence of carcinoma of the kidneyThe American Urological Association (AUA)

NEJM, 2003

Evaluation of microscopic hematuria

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