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Non-Glomerular Causes of Hematuria

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					Non-Glomerular Causes of
      Hematuria


Timothy D. Averch, M.D., F.A.C.S
      Assistant Professor
    Director of Endourology
    Department of Urology
     UPMC Health System
               Objectives
• Learn the differential diagnosis of
  hematuria
• Devise a work-up sequence for patients
  with non-glomerular hematuria
• Be able to outline the treatment modalities
  and outcome for these patients
               Differential
• Trauma
• Stones
• Cancer
• Infection
• Iatrogenic
• Miscellaneous
                    Work Up
• Urinalysis
   – Upper vs. lower tract
• Intravenous pyelogram
   – IVP
• CT scan
   – (-) Contrast or (+/-)
      contrast
• Cystoscopy
• Retrograde urethrogram
  and cystogram
• 90% of work up will be
  negative
    Hematuria from Trauma
• Blunt and penetrating renal trauma
• Ureteral trauma
• Blunt and penetrating bladder trauma
• Rupture of the membranous urethra
• Straddle trauma to the bulbar urethra
• Injury to the penile urethra
        Blunt Renal Trauma
• Etiology
  – MVA‘s
  – Falls
  – Contact sports
• Graded I - V
• With microscopic hematuria
  – Work-up not necessary if hemodynamically
    stable
     • Except children or clinical suspicion
  – CT usually done for other injuries
        Blunt Renal Trauma
            Treatment




• Observation
  – ‗til urine clear
• Surgery
  – Grade V
   Penetrating Renal Trauma

• Stab or gun shot wound
• 88% associated with other organ injury
• After stabilization, surgical exploration
  – Rare to study
          Ureteral Trauma
• Rare
• Deceleration injury or penetrating trauma
• Iatrogenic causes
• Incidental congenital anomalies
  – Uretero-pelvic junction obstruction
• Surgical repair
      Blunt Bladder Trauma
• MVA‘s
• Gross hematuria typically present
• Types
  – Contusion
  – Extraperitoneal rupture
     • 10% of pelvic fxs
     • Tx: bladder drainage
  – Intraperitoneal rupture
     • Surgical repair
• Retrograde urethrogram first
 Penetrating Bladder Trauma

• Stab or gun shot wound
• Diagnostic studies only if stable
• Surgical repair
  Rupture of the Membranous
           Urethra
• 10% pelvic fxs in males
• GROSS BLOOD AT
  MEATUS
• Retrograde urethrogram
• Operative realignment
   – Open or endoscopic
     Straddle Trauma to the
         Bulbar Urethra
• Butterfly hematoma
• Tx: extended drainage
• Long term: stricture disease
  Injury to the Penile Urethra
• Penetrating trauma or sexual activity
  – Fractured penis
• Gross blood
• Retrograde urethrogram
• Open surgical repair
Kidney
  Stones
             Calculus Disease
• One of the most common renal diseases of the
  Western World
• Present in Egyptian mummies dated to 4800 B.C.
• 2 to 4% of the American population are at risk of
  at least one stone episode during his/her life time
• 50% of those will experience at least one further
  episode of stone formation over the ensuing 10
  years
• Stone disease accounts for 1 of every 1000
  hospitalizations
   – 200,000 hospitalizations per year
   – Exceeding $400 million dollars annually
 3 Theories of Stone Formation
• Matrix Theory
   – Organic matrix compounds present in all stones are
     causally related to stone formation
• Inhibitor Theory
   – Deficiency in the urine of substrates which normally
     inhibit crystallization and growth
• Crystalloid or Precipitation-Crystallization
  Theory
   – Supersaturation with respect to the stone-forming
     constituents
• Reality: likely due to a combination of these
  theories
Calcium Oxalate Monohydrate
        or Dihydrate
• Pathogenesis/risk factors
   – Idiopathic
   – Metabolic defects
       • Alkaline urine pH
       • Hypercalciuria
       • Hyperoxaluria
       • Hyperuricosuria
   – Family history
   – Dehydration
   – Diet or medications
       • Vitamins A,D,C
       • Acetazolamide
       • Antacid abuse
              CaOx Features
• Accounts for about 85% of all stones
• Male to female ratio is 3-4:1
• High incidence of stones in the South Eastern
  United States = Stone Belt
• Hypercalciuria
   – > 300 mg/24 hr in males
   – > 250 mg/24 hr in females
• Calcium homeostasis requires
   – hormones: 1,25 vitamin D, PTH
   – organs:   bone, kidney, gut
                  Hypercalcuria
• Increased gut absorption of calcium
   – Increased 1,25 vit D (sarcoid, primary
     hyperparathyroidism)
   – Dietary calcium excess
   – Idiopathic
• Increased bone reabsorption
   – Primary hyperparathyroidism
   – Distal RTA
   – Idiopathic
              Hypercalcuria

• Increased renal excretion
  – Hypercalcemia of any cause

  – Distal RTA

  – Dietary sodium or protein excess

  – Idiopathic hypercalciuria
     • Renal leak
                  Other Hypers
• Hyperuricosuria
  – Uric acid crystals may serve as a nucleus for calcium salt
    precipitation
• Hyperoxaluria
  –   > 40 mg/24 hours
  –   End product of metabolism
  –   Forms an insoluble complex with calcium
  –   NOT pH dependent
  –   Causes: Increased production Increased intestinal absorption
               congenital                 dietary excess
               vitamin C (2 gm/day)       enteric hyperoxaluria
               ethylene glycol            dietary calcium restriction
        Enteric Hyperoxaluria
• Malabsorption syndromes
   – Crohn's disease
   – Intestinal bypass
• Pathophysiology
   – Fatty acid soaps bind calcium in the gut
   – Calcium prevented from complexing with oxalate
   – Oxalate then "free" to be absorbed in large quantities
• Paradoxical treatment
   – Calcium or magnesium supplementation
   – Treat the underlying condition
                 CaOx Dx & Rx
• Diagnosis
  – Stone analysis
  – Calcium oxalate crystals NOT diagnostic
  – 24 hour urine studies
• Treatment
  – Decrease urinary calcium/sodium/oxalate/uric acid
  – Inhibitors
  – Fluids, Rx underlying defect, education
           Calcium Phosphate
• Pathogenesis/risk
  factors
   – Hypercalciuria
      • Vitamin D intoxication
      • Hyperparathyroidism
      • Sarcoid
   – Alkaline urine
      • Urinary acidification
        defect
          – Distal, Type I RTA
      • Acetazolamide
      • Milk-alkali syndrome
             CaPhos Dx & Rx
• Clinical features
   – Common minor constituent of garden variety calcium
     stones
   – Pure calcium phosphate stones are rare
• Diagnosis
   – Stone analysis; crystals NOT diagnostic
   – 24 hour urine studies: hypercalcuria
   – Identify other causative risk factors
• Treatment
   – Decrease calcium excretion
   – Fluids, Rx underlying defect, education
         Urate Nephropathy
• Uric acid stones
   – Most common form of uric acid disposition in the
     urinary tract
• Acute uric acid nephropathy
   –   Particularly malignant form of u.a. precipitation
   –   Chemotherapy for a lymphoma or leukemia
   –   May obstruct of the urinary tubules by sludging
   –   True crystals, or stones do not form
• Chronic urate nephropathy
   – Unrelated to stone disease
   – Progressive disease occurring in a minority of gout
     patients
   – Precipitates in the interstium and pyramids
        • Interstitial nephritis
Uric Acid Calculi
       • Pathogenesis
          – Hyperuricosuria
              • gout
              • psoriasis
              • Lesch Nyhan syndrome
              • obesity
              • Status post chemotx
          – Persistently acid, concentrated
            urine (pH < 5.5)
              • chronic diarrheal disease, esp. via
                ileostomy
          – Uric acid solubility decreases 10-
            20x when urine pH falls 7 to 5
       Uric Acid Calculi Cont’
• Clinical features
   – 5-10% of all stones
   – Only truly radiolucent stone
• Diagnosis
   – Stone analysis
   – Uric acid crystals in the urine NOT diagnostic
   – 24 hour urine studies: hyperuricosuria
• Treatment
   – Very susceptible to solubility conditions
   – Alkalinization to reach urinary pH 6.5-7.0
   – Fluids, Rx underlying condition, education
                   Struvite Stones
• Pathogenesis/risk factors
   – Urinary tract infection with urea-splitting organism
      • Proteus - most common
      • Kliebsiella
      • Serratia
      • Enterobacter
   – Markedly alkaline urine (pH 7.5-8.0)
   – Supersaturation with magnesium-ammonium phosphate
      Struvite Clinical Features
•   Accounts for about 20% of stones
•   Most common cause of staghorn calculi
•   Most common stone in women and paraplegics
•   Recurrent UTIs
    – Bacteria reside in stone
• 40% of struvite stones are mixed calculi
• Sequela
    – Progressive renal insufficiency
    – Urosepsis or perinephric abscesses
    – Obstruction
Struvite Dx & Rx
        • Diagnosis
           – stone analysis
           – struvite crystals diagnostic
             of UTI with urea splitting
             organism
               • NOT struvite stone
           – urinary pH 8 suspect
             struvite stones
        • Treatment
           – antibiotics
           – percutaneous
             surgery/lithotripsy
           – fluids, Rx underlying
             disease, education
                  Cystine Calculi
• Pathogenesis/risk factors
   – Cystinuria
        • Autosomal recessive genetic defect in dibasic amino acid
          transport in renal tubule and gastric mucosa
            – COLA = cystine, ornithine, lysine, arginine
        • Only AA to cause clinical disease
   – 1% of all stones
• Clinical features
   –   Onset often in childhood or early adolescence
   –   Family history
   –   Staghorn calculi can form, mildly radio-opaque
   –   Progression to renal failure
        • Renal parenchymal damage
                     Cystine Dx
• Diagnosis
  – Stone analysis
  – Cystine crystalluria
     • Hexagonal crystals
  – Cyanide-nitroprusside
    test
     • Qualitative
  – 24 hour urine studies
     • Quantitative
     • Homozygous vs
       heterozygous
                      Cystine Rx
• Treatment
  –   High fluid intake (4L/d)
  –   Patient education- compliance
  –   Resistant to ESWL
  –   Alkali therapy
       • Increase in cystine solubility at urine pH > 7.5
  – Penicillamine
       • Covalently bonds to cystine, making a soluble complex
       • Toxic -- glomerulonephritis, SLE syndrome, marrow
         depression
  – -MPG—similar action to penicillamine but better
    tolerated
                Inhibitors
• Deficient in urine of stone-former
• Citrate
  – Forms a soluble Ca+2-citrate complex
  – Increases urinary pH
  – Hypocitraturia occurs in states of chronic
    metabolic acidosis (distal RTA, chronic real
    failure, acetazolamide therapy), K+ depletion
    and idiopathic cases
  – Presumably raises the formation product of all
    types of calcium stones
Clinical Features & Treatment
            Options
• Dull ache in the loin from distention of the renal
  capsule
• Renal "colic" from acute or transient obstruction
   – Lumbar area and radiates around and down into groin,
     testis, labia or thigh
   – Pain changes as calculus moves
   – Patient cannot get comfortable
• Nausea, vomiting, abdominal distention
• Hematuria - gross or microscopic—does not have
  to be present
• Frequency and urgency
• Fever/chills
         Acute Management:
        Diagnostic Procedures
• History and physical examination
   – Risk factors, associated medical conditions,
     medications
• Urinalysis: pH, rbc, wbc, culture, crystals
   – Not all crystals are diagnostic of stone disease
• KUB = x-ray of the abdomen with pelvis
   – Kidney, Ureter, Bladder
• Spiral CT without contrast
   – Current diagnostic test of choice
   – Patients unable to have contrast agents
     Spiral CT Scan without
             contrast
• ―Renal colic CT‖
• ―Kidney stone
  protocol CT‖
• Rapid and specific
  More Diagnostic Procedures
• IVP = intravenous pyelogram
  – Previously best first test
  – Evaluation for obstruction and location
• Ultrasound
  – May diagnose obstruction
  – Locate radio-opaque calculi
  – Limited in ureteral calculi
• Cystoscopy with retrograde pyelograms
        Acute Management: Rx
• 90% of stones less than 5 mm in diameter will
  pass spontaneously
• Increase fluid intake
• Strain all urine to catch stone for analysis
• Antibiotic
• Indications for surgical intervention
   –   Infected system
   –   Obstruction persists >4 weeks
   –   Intractable pain or nausea
   –   Stone unlikely to pass due to size
 Acute Management: Surgery
• If small calculus in the lower or middle third of
  the ureter
   – Ureteroscope with basket or ESWL
   – May need to be fragmented to remove
      • Laser, pneumatic, or electrohydraulic

• If large calculus and/or in the pelvis of the kidney,
  or upper third of the ureter
   – Ureteroscope, percutaneous removal or ESWL
Bladder Stone
                     Surgery
• Extracorporeal Shock
  Wave Lithotripsy
  – Effective and safe
    procedure
  – Revolutionized the
    treatment of all types
    of stone disease
  – Typically first line
    therapy
  – Minimal anesthesia
  – Outpatient
Staghorn Calculi
        • Percutaneous surgery
          alone or with ESWL
        • Recurrence reported at
          10-40%
Percutaneous Nephrolithotomy
         Chronic Management:
         Metabolic Work Up
• Blood chemistry: calcium, phosphate,
  bicarbonate, uric acid, BUN, creatinine
• 24 hour urine collections on "normal" diet
   –   calcium nl to 300 mg in M, 250 mg in F
   –   uric acidnl to 800 mg in M, 750 mg in F
   –   sodium desired 100-125 mEq
   –   volume desired >2000 ml
   –   citrate nl 300-900 mg
   –   oxalate nl < 40 mg
   –   cystine nl < 100 mg
• Stone analysis
    Chronic Management: Rx

• Fluid intake 24 hours/day > 2-3 L/day

• Dietary modification

• Regulate urinary pH

   – Alkalinization: uric acid and cystine stones

   – Acidification almost never indicated
      • Cranberry juice NOT indicated
                Drug Therapy
• Citrate
   – Alkalinization also for calcium phosphate stones
• Thiazide diuretic
   – Decreases urinary calcium for calcium stones
• Sodium cellulose phosphate
   – Binds calcium in the gut for absorbtive hypercalcuria
• Allopurinol
   – Decreases urinary uric acid for uric acid and calcium
     stones
          And More Drugs
• Antibiotics
• D-penicillamine
• -MPG
        Hematuria Of Cancer
• Gross hematuria common
• Cytology
• Bladder cancer- Transitional cell –Uroepithelial
  cell
• Renal carcinoma
• Urethral cancer
   – Only GU cancer more common in females
   – Urothelial in proximal urethra
   – Squamous in distal
  Benign Prostatic Hyperplasia
• Common cause hematuria: turbulent
  flow
• Symptoms determine therapy, not size!
• Meds: alpha blockers
• Surgery
  – Minimally invasive
     • Microwave
     • Laser
     • Radiofrequency
  – Resection (TURP)
  – Open surgery
Renal Cystic Disease
        Simple Renal Cysts
• Not cause of hematuria
Adult Polycystic Renal Disease
•   1 in 500
•   Cause end-stage renal dx
•   Autosomal dominant
•   Involves nephron
•   Other organs
   – Pancreas, spleen, lungs
• HTN common
• Flank pain
• No tx
             Infectious Causes
• Cystitis
• Urethritis
• Prostatitis
• Pyelonephritis
   Miscellaneous Rare Causes
• Instrumentation
• Foreign body
• Anticoagulation
  – Remember: something
    is bleeding
• Chemotherapy
  – Cyclophosphamide
               Conclusions
• Numerous causes
  – Cancer until proven otherwise

• Specific treatments
• Hematuria is the red flag to initiate further
  work up
Thank You!




       Questions?

				
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posted:9/15/2011
language:English
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