Hematuria
Definition
Passage of RBC in the urine. We have to distinguish it from other causes of
urine discoloration, because red urine is not always caused by hematuria.
If hematuria has initially been diagnosed on dipstick, it must always be
confirmed by microscopy.
DD Hematuria
    Microscopic hematuria : From at least 2 properly collected urine
     specimen show >3 RBC/hpf. Transient (UTI), strenuous (exercise),
     spurious (contamination from menstruation and sexual course),
     persistent (true hematuria).
    Macroscopic hematuria : Red brown urine, sometimes with blood clot.
     Always pathologic.
Or
Renal
    Glomerular
        o IgA nephropathy
        o Alport disease and thin basement membrane nephropathy
        o Glomerulonephritis
    Non Glomerular
        o Neoplastic (RCC, benign renal mass)
        o Tubulointerstitial (nephrolithiasis, PKD, pyelonephritis, AIN)
        o Vascular (arterial/ vein thrombosis, Nutcracker syndrome,
           malignant hypertension)
        o Metabolic (hypercalciuria/ uricosuria)
Extrarenal
    Ureter (mass, stone, stricture)
    Bladder (Transitional cell carcinoma, cystitis)
    Urethra (urethritis, traumatic catheterization, stricture)
    Prostate (BPH, prostatitis, cancer)
Some drugs that can cause red urine
    Rifampin
    Chloroquin
    Ibuprofen
    Nitrofurantoin
    Phenytoin
History Taking
Pain associated with infection/ inflammation
Painless associated with tumor or TB
Loin pain  Kidney disease
Colic pain  stone
Suprapubic pain + dysuria + frequency  cystitis
Initial hematuria  suggest bleeding from urethra and prostate
Terminal hematuria  prostate and bladder
Total hematuria  Upper urinary tract
History of familial polycystic kidney dz, TB
Travelling  schistosomiasis
History of catheterization
Check for prostatism
Pelvic injury and fracture
Medication anticoagulant, other drugs
Any history of blood malignancies, malaria and sickle cell disease, hemolysis
Strenuous exercise, muscle injury  myoglobinuria
History of renal biopsy
Abdominal pain with purplish urine  Acute intermittent porphyria
Physical Examination
    Anemia, weight loss  CKD, malignancies
    Palpable abdominal mass  Hypernephroma, distended bladder
    DRE Smooth enlargement of prostate  BPH
      DRE hard craggy prostate  Prostate Ca
    Bone tenderness  Bone meta
Laboratory
    FBC : Decreased Hb in gross hematuria, malignancy. Increased HB in
      polycythemia associated with hypernephroma. Increased WCC in
      infection. Low platelet in blood dyscrasia. High ESR in TB, malignancy.
    Urine microscopy : RBC indicates Hbnuria, ingestion of substance, high
      WCC in infection
    Ureum, Creatinine and electrolyte : Renal failure
    Clotting screen : Anticoagulant therapy, blood dyscrasia
      CXR : Metastasis, TB
      KUB radiograph : Renal calculus
Specific Investigation
    PSA : prostate ca, BPH, prostatitis
    Sickling test : Sickle cell disease
    IVU : Stone, tumor, TB
    US : cystic vs solid, stone, urinary tract obstruction
    CT : tumor, cyst, obstructive uropathy
    Cystoscopy : infection, tumor, stone
    Ureteroscopy : tumor, obstruction
    Renal angiograph : vascular malformation, tumor
    Biopsy : glomerular disease and tumor
Bladder Cancer (Transitional Cell Carcinoma)
Present as painless visible hematuria in older male smoker. Other symptoms
dysuria, blood clots and obstructive symptoms. 90% urothelial cancer.
Risk factor
    Male
    Smoker
    Age >40
    Preexisting urothelial cancer (RCC,
       ureteral, prostate)
    Chronic UTI
    Chemical/ toxin exposure
Diagnostic tools
    Cystoscopy with biopsy : gold
      standard
    Hexaminolevulinate fluorescence cystoscopy : for detection of CIS
    Multiphasic CT Urograph : improve sensitivity of cystoscopy
    US : sensitivity 63%, specificity 99%
Therapy
    Transurethral resection if minimally invasive
    Intravesicular chemotherapy after operation
    Radical cystectomy + cisplatin
Prognosis 10 years survival is 65-72%
Renal Cell Carcinoma (Grawitz)
Present with hematuria, flank pain and renal mass (palpated or seen on
radiograph exam). Usually symptomatic after the disease is advanced. Blood clot
may present, abdominal mass only palpable in thin individual, non tender and
moving with repiration. Fatigue, weight loss, anemia.
Risk factor
    Smoking
    Obesity
    Hypertension
    PKD
Histologically
    Clear cell (75-85%)
    Papillary (10-15%)
    Chromophobe (5-10%)
    VHL tumor supressor gene is mutated in RCC
Diagnostic
    CT scan abdomen : solid renal lesion, thickened irregular walls, also used
      for staging
    US abdomen: does not meet criteria for simple cyst
    Bone scan, CT chest, MRI, PET for distant metastasis
Therapy
    Partial/ complete nephrectomy  biopsy (diagnostic and therapeutic)
    Thermal ablation (cryotherapy)
Prognosis 5 year survival rate
    Stage I >90%
    Stage II 75-95%
    Stage III 59-70%
    Stage IV <10%, median survivor of 16-20 months
IgA Nephropathy
Present with hematuria within 12-72 hours of a (usually) Upper Respiratory
Tract Infection (synpharingitic hematuria). Visible/ non visible hematuria
with proteinuria.
Peak incidence is between 20s-40s, leads to CKD in 25 years. Hypertension and
heavy proteinuria may occur in advance state.
Etiology
     IgA deposition in glomerular mesangium
     No evidence of a role for any specific antigen
Diagnostic
    Immunofluorescence and immuneperoxidase studies for IgA deposits
           o Benign if absence of proteinuria, hypertension or decreased GFR.
           o Severe if proteinuria >500-1000 mg/day, elevated serum
             creatinine, hypertension.
Therapy
    If benign  monitor every 6-12 mo for sign of progression
    If severe  primarily aid at reducing proteinuria and optimizing BP
         o ACEi or ARB optimizing BP and reducing proteinuria
         o Fish oil
         o Very severe  Immunosuppressive agents
         o Renal transplant if already progressed to CKD
Thin Basement Membrane Nephropathy
Hematuria with normal renal function, no or minimal proteinuria. Thinned
GBM on electron microscopy.
Most common cause of persistent hematuria in children and adult.
Etiology
     Defect in type IV collagen
Diagnostic
    Renal biopsy if proteinuria 200-300 mg/ day
    Electron microscopy if no proteinuria, normal renal function
    Immunohistochemical to distinguish TBMN with early Alport syndrome
Therapy
    BP goal <130/80 mmHg
    ACEi if proteinuria >1 g/ day
Prognosis : excellent
Infection related GN
New onset of Nephritic syndrome (hematuria, proteinuria, edema,
hypertension), AKI and infection.
Epidemiology
    Post streptococcal GN occurs in children
    Immunocompromising comorbidities DM, alcoholism.
Etiology
     Mostly associated with Streptococcal pharyngitis and impetigo
     In children 1-2 wks after pharyngitis and 2-4 wks after impetigo
Diagnostic
    ASTO for streptococcal infection
    Hypocomplementemia C3 and C4
      Adult may have nephrotic range proteinuria, hematuria RBC cast, while
       older adult may have sign of volume overload (increased JVP, S3, edema,
       pulmo crackles)
      Biopsy is recommended in adult
Therapy
    Children  Supportive
    Adults
        o Treat underlying infection
        o Antihypertensive, diuretics and sodium restriction for managing
            nephritic complication
Prognosis
    Complete recovery in children
    Adult  CKD
Nephrolithiasis
Rapid onset of excrutiating back and flank pain radiate to abdomen and
groin. Increasing pain with movement, associated with nausea, vomiting, dysuria
and urinary frequency.
Etiology
Stones because of supersaturation in urine  precipitation and crystallization
     Calcium oxalate 75% (hypercalcemic, hyperPTH, excess sodium intake)
     Calcium phosphate (sama kayak Ca oxalate)
     Uric acid (excess dietary purines, MPD, uricosuric agents, metabolic
       syndrome)
     Proteus mirabillis  struvite formation
Complication
    Ureteral obstruction
    Pyelonephritis
    Sepsis
    Renal failure
Diagnostic
    CT scan non contrast
    US for pregnant woman
    Hematuria
Therapy
    Pain control NSAID/ Opidoid
    Hydration oral/ IV
    Uncontrolled pain, nausea and vomiting, AKI  hospitalize
    Sepsis : Broad spectrum Abx and drainage via nephrostomy
    Stone passage
        o Nifedipine and tamsulosine
        o Lithotripsy
    Prevention
          o Reducing phosphate containing soft drinks
          o Stop thiazide, citrate supplementation, allopurinol
BPH
Urgency frequency, nocturia, urge incontinence, stress incontinence, hesitancy,
poor flow, straining, dysuria
Diagnostic using DRE
Therapy
    Diuretics
    Moderate to severe : Alpha bloker (terasozin, doxasozin) + 5alpha RI
       (finasteride), or phosphodiesterase inhibitor (tadalafil)
Prostatitis
Abdominal pain, recent UTI, fever, chills, urinary retention, recent prostate
biopsy
Ascending infection through reflux of urine to prostate through ejaculatory/
prostate ducts.
Eti
     Ecoli, kleb, proteus, pseudomonas
     STD  chlamidya
Diagnostic
     DRE, urinalysis and culture, PSA.
     If abscess occur  CT, MRI, TRUS.
     Renal function
Therapy
     First line Fluoroquinolone, TMP SMX 3-4 wks
     Supportive : pain reliever and stool softener
     Abscess  drainage
Alport Syndrome
Hematuria with strong family history of renal disease and sensory neural
hearing loss
Diagnostic urinalysis with microscopy, SrCr, family history and biopsy.
Dysuria
Pain or burning with or after urination. Most patients with dysuria have a
UTI.
When approaching the DD for dysuria, an anatomic approach to the GUT is
helpful for organization
Skin : Rash causing irritation with urination
    Herpes
    Irritant contact dermatitis
    Syphilitic chancre
    Erosive lichen planus
Urethra : From STI
    Gonorrhea
    Chlamydia
    Trichomoniasis
Male genial structure
    Epididymis : Epididymitis
    Testis : Orchitis
    Prostate : BPH, acute/ chronic prostatitis
Female genital structure
    Vagina : BV, trichomoniasis, candidiasis, atrophic vaginitis
    Uterine/ bladder prolapse
    Cervix : N. gonorrhea, c. trachomatis
Bladder
    Acute cystitis : Uncomplicated (healthy woman without UT abnormality),
      complicated (men, urinary obstruction, pregnancy, neurogenic bladder,
      immunosuppression)
    Interstitial cystitis
Kidney
    Pyelonephritis
Cystitis
Infection of bladder.
Dysuria + Suprapubic pain. Urinary frequency and urgency, hematuria.
No discharge, CVA tenderness, nausea, vomiting, fever. Not associated with
discharge.
Uncomplicated         : Cystitis in healthy woman
Complicated           : Men, urinary obstruction, pregnancy, neurogenic bladder,
immunosuppression
Elderly : incontinence, delirium, functional decline, acute confusion.
Pathogen
    Gram - E. coli (75%), K. pneumonia, Proteus
    Gram + S. saprophtycus, E. faecalis, group B strep
Risk factor : Sexual intercourse, use of spermicide, previous UTI, new sexual
partner
Diagnostic
    Urinalysis (leukocyte, leukocyte esterase  Pyuria, nitrites  gram (-),
      hematuria)
    Urine culture >105 CFU bacteria/ mm, women with cystitis had CFU <102
    CT in women with multiple episode of cystitis with same pathogen
Therapy
    First line Nitrofurantoin/ TMP-SMX
    Quinolon, amoxiclav, beta-lactams
    Uncomplicated 1-5 days
    Complicated 7-10 days
    If symptoms continue within 2 weeks after treatment  Resistance 
      Change antibiotic
    If recur beyond 1 month  Same standard treatment
    Postcoital Abx prophylaxis
Vaginitis
      Atrophic vaginitis : estrogen deficiency, post menopause
      Cervicitis may occur with vaginitis
Therapy
    BV : metronidazole/ clindamycin oral/ IV
    Trichomoniasis : Metro/ tinidazol
    Candida albicans : Topical antifungal or single dose fluconazole
    Atrophic vaginitis : Intravaginal esterogem
Pyelonephritis
Dysuria, flank/ back pain, fever, chills, malaise, nausea, vomiting, CVA
tenderness.
Upper UTI affecting kidney parenchyma.
Because of the ascending infection of the same pathogen that cause cystitis.
Diagnostic
    Urine culture : indicated for all patient suspected with PN.
    Urinalysis : same as cystitis
    CT : indicated if there is concern for concomitant nephrolithiasis/
      obstruction.
Therapy
Outpatient
      Fluoroquinolone first line
      Ceftriaxone, aminoglycoside if quinolone resistance
      7-10 days for uncomplicated, 14 days for complicated
      Follow up
Inpatient if unstable, inability to tolerate oral medication, pregnancy,
immunocompromised, obstruction
      IV quinolone, ceftriaxone, aminoglycoside w/wo ampicillin for 14 days
If fever persist  Imaging CT/ US (perinephric abscess, kidney stone or
obstruction) and broaden abx spectrum.
Cervisitis and Urethritis
Cervisitis : Cervical discharge, dyspareunia, dysuria, post coital bleeding
Urethritis : Dysuria, urethral pruritus, penile discharge, dyspareunia,
abdominal/ testicular pain.
Diagnostic
Urethritis
    Discharge on PE
    Microscopy discharge showing >5 WBC per oil immersion field
    Leukocyte esterase on first void urine
    Microscopy of first void showing >10 WBC per hpf
    Gram stain discharge/ urine culture (+)
Cervisitis
    Mucopurulent endocervical discharge
Urine, ureteral, endocervical, vaginal PCR for GO and chlamydia
Therapy
    Chlamydia : Azithromycin, doxycycline
    GO : Ceftriaxone
    Coinfection of GO-chlamydia is high, treat for both.
    Abstain from intercourse until 1 wk after single dose treatment
    Treat the partner
Urosepsis
Sign of cystitis with lethargy, confusion, orthostasis and SIRS. Hypotension,
thrombocytopenia, hypoxemia, oliguria, metabolic acidosis.
Diagnostic
    Urine dipstick
    Urine culture
    CT scan/ US
Therapy
    Hospitalized, admission to ICU
    IV antibiotics and volume resuscitation with IV fluid to prevent worsening
        sepsis.