haematuria a challanging medical problem.mansfans.com

Urology & Nephrology Center, Mansoura University, Egypt

HAEMATURIA

A Challenging Medical Problem

ByBy

TAREK MEDHAT ABBAS,TAREK MEDHAT ABBAS, MDMDLecturer of NephrologyLecturer of Nephrology

Urology & Nephrology CenterUrology & Nephrology CenterMansoura UniversityMansoura University

EgyptEgypt


Definitions:

Normally the number of RBCs in urine should not be more than 5 RBCs/ high power field on microscopic examination of fresh centrifuged urine sample.

Haematuria

So, haematuria is defined as a secretion of more than 5 RBCs/ HPF in urine.

www.MansFans.com


Detection & quantificationDetection & quantificationof hematuriaof hematuria

Detection & quantificationDetection & quantificationof hematuriaof hematuria

Screening test ( dipsticks )Screening test ( dipsticks ) - 0.02-0.03 mg/dL of Hb, myoglobin- 0.02-0.03 mg/dL of Hb, myoglobin - ~5-20 RBC/mm³- ~5-20 RBC/mm³

Semiquantitative estimationSemiquantitative estimation - centrifugation of 10-15 ml of urine- centrifugation of 10-15 ml of urine - resuspention of sediment in 1 ml of - resuspention of sediment in 1 ml of residual urineresidual urine - high-power microscopy- high-power microscopy

Counting chamberCounting chamber – – the number of cells in 1 microliter of unspun the number of cells in 1 microliter of unspun

urineurine


Classification of hematuriaClassification of hematuria

Macroscopic - MicroscopicMacroscopic - Microscopic

Symptomatic - SymptomlessSymptomatic - Symptomless

Transient - PersistentTransient - Persistent

www.MansFans.com


Haematuria may be the only symptom or may be associated with other manifestations, according to the cause e.g. loin pain and fever with infection and renal colic with renal stones.

Haematuria could be gross (causing red-coloured urine) or microscopic (urine appears normal but RBCs are seen on microscopic examination). In gross hematuria, urine looks red if alkaline, but brown or coca-cola like if urine is acidic due to denaturation of the hemoglobin.


www.MansFans.com


HematuriaHematuriaHematuriaHematuria

Transient phenomenonof little significance

Transient phenomenonof little significance

Sign of seriousrenal disease

Sign of seriousrenal disease

www.MansFans.com


Causes of HematuriaCauses of HematuriaCauses of HematuriaCauses of Hematuria

Kidney diseaseKidney disease

Lesions along the urinary tractLesions along the urinary tract

Conditions unrelated to kidney and Conditions unrelated to kidney and urinary tracturinary tract www.MansFans.com


First: PRE-RENALFirst: PRE-RENAL

Hemorrhagic blood diseaseHemorrhagic blood disease

Sickle cell anemiaSickle cell anemia

Malignant hypertensionMalignant hypertension

Use of anticoagulantUse of anticoagulant

Liver diseaseLiver disease www.Man

sFan

s.com


Haematuria of renal origin:

I. Glomerular haematuria:

Primary glomerular disease (e.g. IgA nephropathy, mesangial proliferative glomerulonephritis or crescentic glomerulonephritis)

Secondary glomerulonephritis i.e. renal involvement is a part of systemic disease

(e.g. post-strephococcal glomerulonephritis, Henoch-Schönlein purpura, SLE, polyarteritis nodosa).


b. Renal infection and tubulointerstitial diseases: Pyelonephritis, renal papillary necrosis, tuberculosis, and toxic nephropathies.

c. Stone disease, idiopathic hypercalciuriad. Renal neplastic diseases: Renal cell

carcinoma, transitional cell carcinoma of the renal pelvis and others.

e. Hereditary renal diseases: Modularly, sponge kidney, polycystic kidney disease, Alport’s syndrome, and thin basement membrane disease.


f. Loin-pain haematuria syndrome.

g. Coagulation defect: use of anticoagulant, liver disease and thrombocytopaenia.

h. Renal vascular disease: Renal infarction, renal vein thrombosis or malignant hypertension.

i. Exertional haematuria.www.MansFans.com


Nephrolithiasis. Malignancy.

Ureteral inflammatory condition secondary to nearby inflammation e.g. diverticulitis, appendicitis or salpingitis.

Ureteral trauma e.g. during ureteroscopy.

Ureteral varices, aneurysms, or arteriovenous malformation.

Haematuria of ureteral origin:


a. Infection: schistosoma, viral or bacterial cystitis.

b. Neoplasm.

c. Foreign body in the bladder e.g. stones.

d. Trauma: During instrumentation or accidental.

e. Drug: e.g. cyclophosphamide induced haemorrhagic cystitis.

Haematuria of bladder origin:

www.MansFans.com


a. Urethritis: foreign body or local trauma to the urethra.

b. Prostate: Acute prostatitis, benign prostatic hypertrophy.

Hematuria of urethral (or associated

structures) origin:

www.MansFans.com


Acute nephritic syndromeAcute nephritic syndrome Acute nephritic syndromeAcute nephritic syndrome

Hematuria Hematuria

Proteinuria Proteinuria

Reduced renal functionReduced renal functionEdemaEdema

HypertensionHypertension

www.MansFans.com


Idiopathic Idiopathic HypercalciuriaHypercalciuria

Idiopathic Idiopathic HypercalciuriaHypercalciuria

Definition:Definition: Calcium excretion > 4 Calcium excretion > 4 mg/kg/daymg/kg/day

Urinary Ca/Creatinine > 0.2Urinary Ca/Creatinine > 0.2

Possible mechanism of hematuria:Possible mechanism of hematuria: microcrystals damaging the tubular or microcrystals damaging the tubular or mucosal epithelia. Resolution of mucosal epithelia. Resolution of hematuria with anticalciuric therapyhematuria with anticalciuric therapy


Alport syndromeAlport syndrome- hereditary disorder of GBM- hereditary disorder of GBM

X-linked dominantX-linked dominant

Autosomal recessiveAutosomal recessive

Autosomal dominantAutosomal dominant ww

w.M

ansF

ans.c

om


Renal diseaseRenal disease

Macro /MicrohematuriaMacro /Microhematuria

ProteinuriaProteinuria

Nephrotic syndromeNephrotic syndrome


Renal failure- malesRenal failure- males

Progressive or juvenile – 20 yProgressive or juvenile – 20 y

Nonprogressive – 40 yNonprogressive – 40 y


Hearing defectsHearing defects

Sensorineural bilateralSensorineural bilateral

Never congenitalNever congenital

Boys- 85% . Girls – 18% < 15yBoys- 85% . Girls – 18% < 15y

Progression of hearing loss parallels Progression of hearing loss parallels renal impairmentrenal impairment


Diagnosis of Alport syndromeDiagnosis of Alport syndrome

Hematuria with or without proteinuriaHematuria with or without proteinuria


Renal failureRenal failure

Ocular defects – anterior lenticonusOcular defects – anterior lenticonus

Familial hematuriaFamilial hematuria

Sensorineural hearing lossSensorineural hearing loss

Progression to renal failure occurring Progression to renal failure occurring in at least one affected subjectin at least one affected subject


ALPORT’S SYNDROME

www.MansFans.com


Familial benign essential Familial benign essential hematuriahematuria

Familial hematuria without Familial hematuria without proteinuria and without progression proteinuria and without progression to renal failure or hearing defectto renal failure or hearing defect

Diffuse attenuation of the GBM is Diffuse attenuation of the GBM is usually considered the hallmark of usually considered the hallmark of the conditionthe condition

It’s non pathognomonic of FBEHIt’s non pathognomonic of FBEH


ContinueContinue

Autosomal dominant traitAutosomal dominant trait

Normal antigenicity of the GBMNormal antigenicity of the GBM


Thin basement membrane Thin basement membrane nephropathynephropathy

HematuriaHematuria

ProteinuriaProteinuria

Attenuation of the GBMAttenuation of the GBM

In children may be AlportIn children may be Alport

In adults m/p benign disorderIn adults m/p benign disorder

www.MansFans.com


HEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHYHEREDITARY NEPHROPATHY

Benign Familial Hematuria

Alport Syndrome

Overlap of histological findingsOverlap of histological findings

The prognosis appears to be depend more on the degree of clinical expression in other members of the family and less

on the histological findings


www.MansFans.com


Hematuria not representing kidney Hematuria not representing kidney or urinary tract disorderor urinary tract disorder

Hematuria not representing kidney Hematuria not representing kidney or urinary tract disorderor urinary tract disorder

Following exerciseFollowing exercise

Febrile disorders Febrile disorders

Gastroenteritis with dehydrationGastroenteritis with dehydration

Contamination from external Contamination from external genitaliagenitalia


Transient microscopic haematuria is relatively common. Up to 39% of adults between ages of 18 and 33 may have microscopic haematuria at least once, and up to 16% may have it in two or more occasions. Therefore, an extensive workup is not warranted except in high-risk patients, > 50 years of age and those patients with other clinical or urinary abnormalities.


Initial is usually urethral.

Terminal hematuria is usually prostatic or bladder origin.

Total hematuria is either bladder ureteral or renal origin.

Patterns Of Haematuria

www.MansFans.com


Differential Diagnosis of Haematuria:A. First, haematuria should be differentiated

from other causes of red or brownish urine:Dipsticks (Hemastix) will be positive with

haematuria, hemoglobinuria (hemolysis) and with myoglobinuria (muscle damage) but negative with other causes e.g. prophyrins (in porphyria), bile (in jaundice), melanin (in melanoma), alkaptonuria, food dyes and drugs as PAS or phenylphthalein.

Microscopy will show RBC’s only with haematuria.


False positive test for haematuria:

Haemoglobinuria.

Myoglobinuria.

Ascorbic acid.

False negative test for hematuria:

Highly diluted urine.


Haematuria could be glomerular (because of glomerular disease, sometimes called medical); or non glomerular (sometimes called surgical).

1. The shape of RBCs in urine are small and dysmorphic in cases with glomerular haematuria while it will be normal in case of non glomerular haematuria.

Glomerular haematuria could be differentiated from non glomerular haematuria by:


2. Means corpuscular volume of RBCs in urine of patient with glomerular haematuria is smaller (< 72 FL) than that in peripheral blood, but in non glomerular cases is equal.

3. Proteinuria is present in most cases of glomerular hematuria but not in cases of non glomerular hematuria.

4. Casts, especially red cell casts are seen in glomerular haematuria.

5. Blood clots indicate non-glomerular bleeding and can be associated with pain & colic.

6. Three-glass test.


Glomerular versus extraglomerular Glomerular versus extraglomerular bleedingbleeding

Urinary findingUrinary finding GlomerularGlomerular ExtraglomerularExtraglomerular

Red cell castsRed cell casts May be presentMay be present AbsentAbsent

Red cell Red cell morphologymorphology

DysmorphicDysmorphic UniformUniform

ProteinuriaProteinuria May be presentMay be present AbsentAbsent

ClotsClots AbsentAbsent May be presentMay be present

ColorColor May be red or May be red or brownbrown

May be redMay be red


Isolated HematuriaIsolated Hematuria(microscopic)(microscopic)

Isolated HematuriaIsolated Hematuria(microscopic)(microscopic)

No other urinary abnormalitiesNo other urinary abnormalities

No renal insufficiencyNo renal insufficiency

No evidence for systemic diseaseNo evidence for systemic disease

Incidence ( school-aged children )Incidence ( school-aged children )

4-6% - single urine examination4-6% - single urine examination

0.5-1% - repeated testing over 6-12 0.5-1% - repeated testing over 6-12 monthsmonths


Etiologies of isolated HematuriaEtiologies of isolated HematuriaEtiologies of isolated HematuriaEtiologies of isolated Hematuria

GlomerularGlomerular - - Benign Recurrent or Persistent Hematuria Benign Recurrent or Persistent Hematuria 1.Sporadic1.Sporadic 2.Familial2.Familial - IgA Nephropathy- IgA Nephropathy - Alport syndrome- Alport syndrome - PSAGN- PSAGN

Non-glomerularNon-glomerular - Idiopathic Hypercalciuria- Idiopathic Hypercalciuria - Cystic Kidneys- Cystic Kidneys - Urinary Tract obstruction- Urinary Tract obstruction - Tumors- Tumors - Trauma- Trauma

www.MansFans.com


Hematuria with familial associationHematuria with familial associationHematuria with familial associationHematuria with familial association

GlomerularGlomerular - Benign Familial Hematuria - Benign Familial Hematuria - Alport syndrome- Alport syndrome

Non-glomerularNon-glomerular

- Idiopathic Hypercalciuria- Idiopathic Hypercalciuria - Polycystic Kidney Disease- Polycystic Kidney Disease - Urolithiasis- Urolithiasis - Tumors- Tumors


First exclude haemoglobinuria and myoglobinuria since both of them can also cause positive dipstick test for haematuria. This is done by microscopic examination of fresh urine sample. In case of haematuria, RBCs could be seen while in the other two conditions no RBC’s could be seen.

Approach to a case of haematuria


In case of myoglobinuria, clinical examination may show manifestations of muscle disease and the examination of urine by immunoelectrophoresis may show myoglobin.

In case of haemoglobinuria, manifestations of haemolysis may be evident


Evaluation of HematuriaEvaluation of Hematuria HistoryHistory

Evaluation of HematuriaEvaluation of Hematuria HistoryHistory

Detailed review of family historyDetailed review of family history hematuriahematuria proteinuriaproteinuria renal insufficiencyrenal insufficiency deafnessdeafness stonesstones

Precipitating factorsPrecipitating factors infectioninfection exerciseexercise

Abdominal painAbdominal pain HSPHSP hydronephrosishydronephrosis pyelonephritispyelonephritis urolithiasisurolithiasis


History Taking History Taking

Past history Past history （（ previous episodes, recent previous episodes, recent 　　 food and drug ingestion, exercise, food and drug ingestion, exercise, 　　 instrumentation, menstruation…instrumentation, menstruation… ））

Dysuria ? Dysuria ? Associated bladder irritability or flank pain ?Associated bladder irritability or flank pain ?

Time of hematuriaTime of hematuria initial:initial: urethritis, stricture, meatal stenosisurethritis, stricture, meatal stenosis total:total: bladder, ureter, kidneybladder, ureter, kidney terminal:terminal: bladder neck or prostatic urethrabladder neck or prostatic urethra


History Taking (2)History Taking (2)

Associated symptomsAssociated symptoms Fever, chills, other bleeding point, dyspnea, Fever, chills, other bleeding point, dyspnea, recent URI, recent URI,

Painful hematuria:Painful hematuria: stone, inflammation, cancer stone, inflammation, cancer bladder, cancer prostate, SEP, traumabladder, cancer prostate, SEP, trauma

Painless gross hematuriaPainless gross hematuria consider tumorconsider tumor


Evaluation of HematuriaEvaluation of HematuriaPhysical ExaminationPhysical Examination

Evaluation of HematuriaEvaluation of HematuriaPhysical ExaminationPhysical Examination

I- GENERAL EXAMINATION:I- GENERAL EXAMINATION:Growth failureGrowth failureHypertensionHypertensionPallorPallorEdemaEdemaRashRashExamination of the skin for hemorrhagic Examination of the skin for hemorrhagic

spotsspotsAbdomen: search for a mass or tendernessAbdomen: search for a mass or tendernessGeneral manifestations of the causeGeneral manifestations of the cause


LOCAL EXAMINATIONLOCAL EXAMINATION

• External genitalia: bleedingExternal genitalia: bleeding

infectioninfection

traumatrauma

PR examination: prostate or bladder causePR examination: prostate or bladder cause

Suprapubic tenderness or massSuprapubic tenderness or mass

Tender loinTender loin

Palpable renal massPalpable renal masswww.MansFans.com


INVESTIGATIONSINVESTIGATIONS

www.MansFans.com


Study of hemorrhagic profileStudy of hemorrhagic profile

Blood picture:Blood picture:

Sickle cell anemiaSickle cell anemia

LymphomaLymphoma

leukemialeukemia


Urine analysisUrine analysis

Volume:Volume: low in nephritic syndrome low in nephritic syndrome

Colour:Colour: red in macroscopic hematuria, red in macroscopic hematuria, smokey in nephritic syndromesmokey in nephritic syndrome

Bilharzial ovaBilharzial ova

CrystalsCrystals

Malignant cellsMalignant cells


Examination of urine for:

Proteinuria.

Casts.(RBC in nephritic syndrome, PUS

cells in UTI, WBC in pyelonephritis)

Pus.

Bacteria (specific and non specific)

Culture (Ordinary and special)

PCR (TB-DNA)


Ultasound, plain X-ray, I.V.P. (if serum

creatinine is normal), CT, MRI and

possibly angiography, for the diagnosis

of surgical diseases e.g. stone,

malignancy, infection, or

malformations.

Radiological investigationsRadiological investigations


RBCs in urine could be examined for its shape to differentiate glomerular (small, distorted) from non glomerular causes (by phase contrast microscopy).

Kidney function tests.

Specific investigations for diagnosis of systemic disease causing haematuria e.g. SLE.

Endoscopic study: to diagnose neoplastic disease , UB ulcers

Kidney biopsy: for glomerular haematuria.

OTHER INVESTIGATIONS


www.MansFans.com

Yes

Dipstick+Dipstick+ Uriinalysis (UA) with microscopy

RBCs present

•Hemoglobinuria•Myoglobinuria

Appropriate work up and therapy

NO

YesTransient cause?•Sexual intercourse• Infection•GU instrumentation

•Menstruation•Vigorous exerciseYes

Age < 50

Surveillance

Persistent hematuria

Glomerular etiology?•Proteinuria > 500 mg/24 hr•UA shows RBC casts +/- dysmorphic RBCs•Renal insufficiency

NO

Imaging:•Ultrasound •Spiral CT

•Mass•Stricture

•Hydronephrosis

Urology referral

•Cysto+/-•Cytology

•Age > 50•Aromatic amine exposure•smoker

Repeat UA when condition resolved

Nephrology referral

Biopsy

Cystic disease

Nephrology referral

Evaluation of haematuria


Work-up of a child with Work-up of a child with HematuriaHematuria

Work-up of a child with Work-up of a child with HematuriaHematuria

Phase IPhase I:: • Urinalysis ( sediment examination )Urinalysis ( sediment examination )• RBC’s morphologyRBC’s morphology• Urine cultureUrine culture• BUN, Creatinine, Proteins, Electrolytes BUN, Creatinine, Proteins, Electrolytes • Antibodies against strept. & other antigensAntibodies against strept. & other antigens• Complement, ANF, ImmunoglobulinsComplement, ANF, Immunoglobulins• Renal USRenal US• Urinalysis of 1Urinalysis of 1stst degree relatives degree relatives• 24h urine collection: Ca, Creat.,Protein, UA24h urine collection: Ca, Creat.,Protein, UA

Phase IIPhase II:: • Hearing testHearing test• CystoscopyCystoscopy• Renal biopsyRenal biopsy

www.MansFans.com


Isolated hematuriaIsolated hematuriaIsolated hematuriaIsolated hematuria

The child needs to be monitored for the The child needs to be monitored for the appearance of new clinical signs:appearance of new clinical signs:

hypertensionhypertension proteinuriaproteinuria changes in the pattern or severity of hematuriachanges in the pattern or severity of hematuria

If there is no change in the first year,observation If there is no change in the first year,observation at at yearlyyearly intervals is adequate intervals is adequate


Isolated hematuriaIsolated hematuria Possible Possible outcomeoutcome

Isolated hematuriaIsolated hematuria Possible Possible outcomeoutcome

Disappearance of hematuriaDisappearance of hematuria

Hematuria will persist -Hematuria will persist -

follow-up should be continuedfollow-up should be continued

The hematuria will no longer be The hematuria will no longer be “isolated” - further investigation“isolated” - further investigation


Most common causes of hematuria by age and Most common causes of hematuria by age and sexsex

Age/sex Age/sex Common causesCommon causes0-20 AGN, UTI, 0-20 AGN, UTI,

congenital urinary tract congenital urinary tract anomalies with obstructionanomalies with obstruction

20-40 male UTI, stones, bladder tumor20-40 male UTI, stones, bladder tumor40-60 female bladder tumor, stone, UTI40-60 female bladder tumor, stone, UTI>60 male BPH, bladder tumor, UTI>60 male BPH, bladder tumor, UTI>60 woman Bladder tumor, UTI>60 woman Bladder tumor, UTI


1. Treatment of the cause.

2. Haemostatic e.g.: Cyclokapron. Vitamin K DDAVP Frish frozen plasma.

3. Haematenics and blood transfusion.

Treatment Of Haematuria

haematuria a challanging medical problem.mansfans.com

Documents