Hematuria

Approach to Hematuria

See figure.

Sometimes urine becomes red with Hb rather than blood. This may be induced by vigorous exercise in young people e.g. prolonged marching in soldiers (march hemoglobinuria). These patients are believed to defective RBC membranes which makes them more vulnerable to trauma.

Nephrologic Urologic Symptoms

Constitutional: if 2 to systemic disease. Arthralgia. Rash. Deafness (Alport’s synd). Pain. Gross blood. Prostatism. Signs increase BP (occasionally). Urine Protein. Casts. RBCs only. Labs increase Creatinine (occasionally). Normal Creatinine (unless obstructed). Possible Investigations (depending on setting): Serum complement, ASO, ANA, ANCA, Anti-GBM antibodies, cryoglobulins, Hep B and C, HIV.

N.B. Make sure that: Female patients have not mistaken menstrual bleeding for hematuria. You rule out facititious causes.

Diagnostic Features

Stage of micturition at which blood appears is sometimes diagnostically useful. Blood from kidneys, ureters, bladder wall: will completely mix with urine and be present throughout urinary stream. Urethral bleeding: o may leak out independently of micturition. OR may be seen only at beginning or end of urinary stream. Blood arising from bladder beck / posterior urethra: may sometimes present as terminal hematuria.

IX:

1.Likely source may be suspected from Hx and P/E.

2.Urinalysis; looking for:

Dipstick testing for hematuria is extremely sensitive and yields many false +) result +) dipstick result should be confirmed by microscopy of a fresh urine (which can also check for infection). Presence of RBCs casts / dysmorphic (abnormally shaped) RBCs Glomerular bleeding. = RBCs are deformed by mechanical and osmotic stress as they pass through tubules. Heavy proteinuria suggests glomerular lesion.

3. Microscopic examination of urine: WBC casts Renal inflammation. Bacteria may be seen and culture should be performed.

4.Urine should always be sent for cytology.

5.Plasma Urea (BUN) and plasma Creatinine: Assess renal function.

6.Plain abdo film and US of renal tract: Assess renal size and look for structural lesions (calculi, tumors, cysts).

A lesion of renal tract is suspected if: (a)patient is old. (b)No evidence of intrinsic renal disease.

Proceed to cystoscopy with IVU (if upper renal tract has not been clearly identified by US).

Normal urine (centrifuged deposit) contains:

1. RBCs 1 X 106 cells / 24 hrs (3 / HPF).
2. WBC’s 2 X 106 cells / 24 hrs (6 / HPF).
3. Hyaline casts = uromucoid (Tamm-Horsfall protein which is excreted by normal tubular cells).
4. Cellular casts result from adherence of either: RBCs (implying glomerular bleeding). OR WBC’s (implying tubular inflammation) to surface of hyaline casts.
5. Epithelial cells may be found in normal urine due to contamination by cells from vulva / prepuce.

   Case History

   History: An 80-year-old woman is admitted to hospital with a fractured neck of femur. Routine urine testing by the ward nurse reveals blood (++++). A specimen collected in a bottle shows obvious pink discoloration. Pt has never noted bloody urine, nor has she complained of urinary symptoms.

   P/E: She is not pale or pyrexial. No systemic signs of renal disease No Renal angle or supra-pubic tenderness. Kidneys are not palpable.

   Investigations (Ix): Reveal a mild iron deficiency anemia. Slightly raised serum creatinine. Urine microscopy shows numerous red cells but few white cells and bacteria. Culture of urine is (-)ve. Plain abdominal radiograph reveals no ureteric stones and the kidney outline is normal. Kidney US is normal. IVU shows normal upper renal tract, but there’s mucosal irregularity of bladder mucosa. Flexible cystoscopy reveals bladder papillomas which are biopsied.

   Comments:

   1. The absence of pain and dysuria does not exclude infection. Urine microscopy and culture is necessary.
   2. In GN, hematuria is a/w biochemical evidence of kidney failure.
   3. Bleeding with kidney stones is usually painful syndrome and 90% of renal and ureteric stones are visible on a plain radiograph.
   4. Kidney tumors are usually visible on US and contrast urography. Cystoscopy allows direct visualization and biopsy of bladder.

   Self-Assessment Multiple Choice Questions.

   Choose the BEST answer:

   1.Microscopic hematuria is an expected finding in all the following conditions except:

   1. Infective endocarditis.
   2. Renal infarction.
   3. Renal amyloidosis.
   4. Papillary necrosis.
   5. Post-infectious glomerulonephritis

   2. A 40-year-old man has the sudden onset of severe right flank pain that comes in waves all night long. When he is seen in the emergency room, after waiting for two hours, he is exhausted. His urine specimen is examined by dipstick in the emergency room, and this reveals no ketones, glucose, protein, nitrite, or urobilinogen; however, blood is present, but few WBC’s. The specific gravity is 1.015 and the pH is 5.5. The most probable diagnosis is:

   1. Benign prostatic hyperplasia.
   2. Benign prostatic hyperplasia.
   3. Ureteral calculus.
   4. Renal angiomyolipoma.
   5. Transitional cell carcinoma (TCC) of bladder.

   3. A 40-year-old male has severe lower abdominal pain one evening. He notes the presence of bloody urine. Physical examination reveals no abdominal tenderness or masses, and bowel sounds are active. An abdominal CT scan reveals a small bright rounded object in the region of the left ureter. The underlying cause for these findings is most likely to be:

   1. Hypercalciuria.
   2. Hyperparathyroidism.
   3. Urinary tract infection.
   4. Gout.
   5. Cystinosis.

   4. A 10-year-old girl was brought by her parents to their family physician. History revealed that the child had a sore throat for about 10 days prior to the office visit. Initial laboratory tests ordered by the family physician revealed an elevated BUN and creatinine. A microscopic urinalysis showed hematuria with dysmorphic RBC’s. The light microscopic appearance of the renal biopsy showed hypercellularity, with PMN’s present, and there were subepithelial electron dense “humps” seen by electron microscopy. What additional laboratory finding is most likely to be present in this setting?

   1. Elevated serum glucose.
   2. Antibody to double stranded DNA.
   3. Antiglomerular basement membrane antibody.
   4. Positive C3 nephritogenic factor.
   5. Elevated antistreptolysin O titer.

   5. A 59-year-old man notes blood in his urine, which is confirmed by urinalysis, but there is no proteinuria or glucosuria. A urine culture is negative. A cystoscopy is performed, and a 3 cm exophytic mass is noted in the dome of the bladder. A biopsy of this mass reveals fibrovascular cores covered by a thick layer of transitional cells. Which of the following risk factors is most likely to have led to development of this lesion?

   1. Diabetes mellitus.
   2. Recurrent urinary tract infection.
   3. Therapy with methicillin.
   4. Cigarette smoking.
   5. Tuberous sclerosis.

   6. If the urine dipstick test for blood is positive but no red blood cells are seen by urine sediment microscopy, a diagnosis to strongly consider is:

   1. Post-streptococcal glomerulonephritis.
   2. Renal papillary necrosis.
   3. Ureteral lithiasis.
   4. Myoglobinuria.
   5. Renal infarction.

   7. A 19-year-old male notes hematuria and sees his physician, who also notes mild proteinuria on a urinalysis specimen. There is no blood, glucose, or ketones noted in the urine. Additional examination, including audiometry, reveals only hearing loss. Which of the following findings is LEAST likely to be present?

   1. Other affected family members.
   2. Basement membrane abnormalities.
   3. Immune complexes in the mesangium.
   4. Increased risk for renal failure in 10 years.
   5. Visual problems

   8. A 50-year-old male with a long history of smoking has a routine urinalysis performed that demonstrates pH 5.5, specific gravity 1.013, 2+ blood, no protein, and no glucose. A urine cytology is performed and he has atypical epithelial cells seen. A urologist performs a cystoscopy, but no mucosal lesions are noted. Which of the following conditions best explains these findings?

   1. Adenocarcinoma of prostate.
   2. Transitional cell carcinoma of renal pelvis.
   3. Acute interstitial nephritis.
   4. Nodular glomerulosclerosis.
   5. Squamous cell carcinoma of penis.

   Challenging question!

   9. A 55 year old male who complains of some dull flank pain has a urinalysis performed that demonstrates microscopic hematuria. A CBC is performed and shows WBC count 7800/ﾵL, Hgb 21.1 g/dL, Hct 63.5%, MCV 94 fL, and platelet count 195,000/microliter. His serum urea nitrogen is 20 mg/dL and creatinine 1.4 mg/dL. Which of the following radiographic findings is most likely to be present?

   1. Hydronephrosis and hydroureter on intravenous pyelogram.
   2. An 8 cm right renal lower pole mass on abdominal CT scan.
   3. Radiopaque ureteral calculus on an abdominal plain film.
   4. Enlarged, multicystic kidneys on abdominal ultrasound.
   5. An 11 cm pelvic mass below the bladder on MRI scan.

      Answers to the MCQ’s

      1. C) In renal amyloidosis, proteinuria is typical presentation. B) There may be frank hematuria. D) Risk factors include diabetes mellitus, NSAID usage and alcoholism.

      2. C) These acute symptoms are typical of a calculus that is being passed. A) BPH may result in urinary tract obstruction that favors infection, but these symptoms are more acute, and few WBC’s are seen. Obstruction per se does not lead to calculus formation. B) Membranous GN typically produces a nephrotic syndrome without acute symptoms. D) These tumors are slow growing and unlikely to produce acute symptoms. E) Though a TCC could result in hematuria, it is not likely to produce such acute symptoms.

      3. A) Most urinary tract stones contain calcium. The concentration of calcium must exceed the solubility in the urine. B) Although there can be increased excretion of calcium and stones with hyperparathyroidism, many cases are idiopathic. C) Urinary tract infections are more often associated with magnesium ammonium phosphate (‘struvite’) stones. These constitute about 15% of urinary tract calculi. D) Sodium urate stones account for only about 5% of urinary tract calculi. E) Cystine crystals are very uncommon, because cystinosis is uncommon.

      4. E) This hypercellular glomerulus has many neutrophils, characteristic for a post-infectious glomerulonephritis, for which a nephritogenic strain of Streptococcus is a likely etiology.

      5. D) He has a transitional cell carcinoma of the urinary bladder, and smokers are at increased risk for this cancer. These cancers can be multiple and recurrent.

      6. D) The dipstick test is sensitive for both hemoglobin and myoglobin.

      7. C) He has hereditary nephritis (Alport’s syndrome), which is not associated with immune complexes. Mesangial matrix, however, is increased, and epithelial cells may appear foamy. It is either X-linked or autosomal dominant in most families. It leads to glomerular capillaries with irregular basement membrane thickening and attenuation with splitting of the lamina densa. Symptoms usually appear at ages 5 to 20, with overt renal failure between ages 20 to 50. It is associated with corneal dystrophy, lens dislocation, and posterior cataracts.

      8. B) The lack of findings in the bladder, but the presence of atypical cells, suggests that the lesion is located higher. A) Adenocarcinoma of prostate does not typically shed atypical cells into urine. C) Inflammatory changes may sometimes produce some degree of atypia, but the history of smoking strongly suggests that a neoplasm may be present. D) No atypical cells would be produced by this lesion. E) This lesion would be diagnosed by visual inspection.

      9. B) The polycythemia suggests a paraneoplastic syndrome, and a renal cell carcinoma is a likely candidate for the primary lesion. The flank pain and hematuria can be explained by a renal cell carcinoma. A) Dilation of the ureters and renal pelves would suggest an obstructive uropathy with chronic renal failure, not polycythemia. C) A ureteral calculus is likely to produce excruciating pain as it passes. D) Dominant polycystic kidney disease results in chronic renal failure. There may be occasional pain associated with hemorrhage or rupture of one of the cysts. E) Such a large mass could produce obstruction. It is possible for a large prostatic adenocarcinoma to do this, or a rhabdomyosarcoma in a child.

      Pix required: 1. Diagram for causes of Hematuria in Essential Surgery. 2. Cystoscopy in a standard Radiology Atlas (esp. for bladder papilloma) 3.

      References:

      1. Ferri FF, Practical Guide To The Care Of The Medical Patient, 5th ed, Mosby, 2001.
      2. Yue J, Ahuja G, Toronto Notes: MCCQE 2001 Review Notes, 17th ed, University of Toronto Press, 2001.
      3. Rubenstein D, Wayne D, Bradley J. Lecture Notes On Clinical Medicine, 5th ed, Blackwell Science, 1997.
      4. Browse NL, An Introduction To The Symptoms And Signs Of Surgical Disease, 3rd ed, 1997.
      5. Epstein O, Perkin GD, de Bono DP, Cookson J, Clinical Examination, 2nd ed, Mosby, 1997.
      6. Burkitt HG, Quick CRG, Gatt D, Essential Surgery: Problems, Diagnosis and Management, 2nd ed, Churchill Livingstone, 1996.
      7. Amirlak I, Dawson KP, Renal Assessment For The Paediatrician: Interpretation Of Urinalysis. Middle East Paediatrics 2000; 5 (1): 16-17.

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