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Objectives
Define and classify hematuria. Review the pathophysiology of
hematuria.
The Problem
A 40 year old woman presents for a yearly healthmaintenance examination. She is not currently on her menstrual period. On her dipstick urinalysis, she has 2+ blood, trace protein, trace leukocyte esterase and negative nitrates.
Definitions
Hematuria is defined as three or more RBCs per highpowered field on urine microscopy, from 2 of 3 specimens.
In this photo, arrows point to WBCs surrounded by monomorphic RBCs.
Journal of Urology, February 2010: Retrospective analysis of 320 new patient visits to a urology office with the diagnosis non-macroscopic hematuria. Of these referrals, only 41% had had microscopic urinalysis prior to referral, and only 24% had 3 or more RBCs/hpf.
Unnecessary Referrals
The Medicare cost of working up these 69 patients without microscopic confirmation was approx. $45,000. Thirty-five of the 69 underwent cystoscopy; only one (with true hematuria) had a malignancy. Moral of the story: Confirm hematuria with microscopy!
Take-Home Point #1: Positive dipsticks for blood should get microscopic confirmation.
Beeturia
Rhubarburia Medications (phenazopyridine, methyldopa, senna, others) Porphyria
CLINICAL
Gross
Classification
frankly bloody
Macroscopic
red urine
PATHOPHYS
Glomerular
Non-Glomerular
History
Age is probably the most important factor.
Pain? Quality, radiation, severity, etc. + unilateral flank pain: urolithiasis, clot (or CA). Zebra: loin pain-hematuria syndrome - 1967 report, ?focal renal cortical ischemia, prevalence ~0.012%
Review of systems: weight loss, rash, joint pain, fatigue, edema. + recent URI: think PSGN or IgA nephropathy
Uncommon
Factitious Fever HUS Hemophilia HSP Schistosomiasis
0 to 15
15-50
AVMs or fistulae DIC Goodpastures syndrome Loin pain-hematuria syndrome Renal infarction Renal vein thrombosis Schistosomiasis Medullary sponge kidney AVMs or fistulae Cyclic hematuria in women Endometriosis TTP Renal vein thrombosis Toxins (cantharidin, djenkol bean) LP-HS
>50
History (cont.)
Recent exercise or trauma?
Recent travel? (Especially to Africa, Middle East or India.) PMH: coagulopathies (acquired or hereditary), irradiation, chemo. Family Hx: hereditary nephritis, PKD, sickle cell disease. Social Hx: smoking, industrial exposures (tetraethylchloride, benzene, aromatic amines)
RED FLAGS
Smoking history Occupational exposure to chemicals or dyes (benzenes or aromatic amines) History of gross hematuria Age >40 years (>50, some sources say) History of urologic disorder or disease (not simple UTIs) History of persistent irritative voiding symptoms History of recurrent or chronic urinary tract infection Analgesic abuse History of pelvic irradiation
Source: Urology 2001;57(4)
Physical Examination
Vitals
Heart
Lungs
crackles, rhonchi? (Goodpastures syndrome)
Abdomen
masses? (cancer, obstruction) bruits? (renal ischemia)
Extremities
Rectal
BPH? nodules? (cancer) tenderness? (prostatitis, endometriosis)
Take-Home Point #2: Most serious hematuria is going to be due to: 1. Infection (UTI, prostatitis) 2. Stones 3. Malignancy (anywhere along the urinary system)
Welcome to...
A 7 year old boy presents 2 weeks after an episode of pharyngitis because his mother noticed his urine was red. He has mild edema on examination.
1. Schistosomiasis 2. Goodpastures syndrome 3. Post-streptococcal glomerulonephritis 4. Prostatitis
A 50 year old man presents with 1 week of vague pelvic discomfort, urinary hesitancy, frequency and nocturia. His examination reveals a temperature of 38.1 C and a tender, boggy prostate. His urinalysis shows 20-30 RBCs/hpf without pyuria or crystals.
A 38 year old woman with chronic pelvic pain presents with macroscopic hematuria. She has no fever, dysuria or flank pain. She notes that her urine only turns dark red with or soon after her menstrual cycle.
1. Endometriosis 2. Exercise-induced hematuria 3. Polycystic kidney disease 4. Polycystic ovarian disease 5. Both B and C
A 28 year old man presents to the ER with the sudden onset of unilateral, severe flank pain radiating to the ipsilateral groin. He is afebrile, but diaphoretic and nauseous. His urine dipstick shows 3+ blood and trace leukocytes.
1. 2. 3. 4.
An 82 year old man presents to the ER with the sudden onset of unilateral, severe flank pain radiating to the ipsilateral groin. He is afebrile, but diaphoretic and nauseous. His urine dipstick shows 3+ blood and trace leukocytes.
1. 2. 3. 4. 5.
Drug-seeker Urolithiasis Dissecting AAA Post-streptococcal GN Probably B, but I want to rule out C
Take-Home Point #3: Look for typical clusters of symptoms and signs to quickly and roughly differentiate between infection, stones and cancer.
Is it glomerular or nonglomerular?
Glomerular:
acanthocytosis (acantho, thorn or spike) or casts.
Non-glomerular:
isomorphic RBCs.
Glomerular Acanthocytes
If its glomerular...
Again:
acanthocytes or casts in the sediment...
If its nonglomerular...
Again, regular-appearing, isomorphic RBCs. Ask: where, then, is the bleeding from? Step 1: CT urogram. Looks for the big anatomical lesions.
If no lesion, then--
Step 3: Is the patient high-risk for malignancy--over 40, toxic exposures, irradiation, etc.? if yes, go to cystoscopy anyway and consider repeating cytology at 6, 12, 24 and 36 months.
CT Urography
Journal of Urology, March 2008: Retrospective review of the radiologic, pathologic and urologic records of 468 patients without prior hx of GU cancer. All underwent CT urogram. 50 urinary system neoplasms diagnosed, with CT-U finding 32/50. Sensitivity = 64%, specificity = 98%, PPV = 76%, NPV = 96%. Conclusion: CT-U is moderately sensitive and highly specific for GU neoplasm, but does not replace cystoscopy and urine cytology in high-risk patients with hematuria. In other words: very helpful if abnormal, not very reassuring if normal.
A 55 year old male smoker with isolated microscopic hematuria (no fever, pyuria or prostate symptoms) has isomorphic RBCs, no casts or acanthocytes on urine micro. What test would you order first?
1. 2. 3. 4.
If the test you ordered in the last question failed to show a lesion, which referral would be most appropriate?
1. 2. 3. 4. 5.
Top 3 Suspects are: Infection, Stones and Malignancy. Look for Illness Scripts
ex: unilateral flank pain, afebrile, N/V (stones) ex: hematuria correlated with menses (endometriosis) ex: obstructive sxs, fever, prostate tenderness (prostatitis) ex: CVAT, fever, dysuria (pyelo)
If its not easy, ask: Glomerular or Not? Glomerular - protein or renal dz? If so, refer to nephrology. Not - 1. CT-U; 2. Cytology; 3. Cystoscopy.
References
Beers MH, et al., Merck Manual of Diagnosis and Therapy (18th print and online editions), Chapter 226: Approach to the Genitourinary Patient: Isolated Hematuria. Cohen RA and Brown RS, Microscopic Hematuria, New England Journal of Medicine, 348:23, 5 June 2003. Grossfeld GD, et al., Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy recommendations. Part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up, Urology 2001; 57(4). Kaplan M, et al., Essential Evidence Plus Online (www.essentialevidence.com), Hematuria, updated 9-11-2009, and Rauta V, EBM Guideline: Haemat-uria (6-32003). Rao PK, et al., Dipstick Pseudohematuria: Unnecessary Consultation and Evaluation, J Urol, 2010 February; 183(2). Rose BD, et al., UpToDate Online(www.uptodate.com), v. 17.3, Evaluation of Hematuria in Adults. Sudakoff GS, et al., Multidetector CT Urography as the Primary Imaging Modality for Detecting Urinary Tract Neoplasms in Patients with Asymptomatic Hematuria, J Urol, 2008 March, 179(3). Zepf B, Evaluation of Patients with Microscopic Hematuria, American Family Physician, 1 March 2004. Schrute D, Beets and Urine Pennsylvania Beet Farms, vol 3, no. 6.
Thank You!