Congenital extrahepatic portosystemic shunts

WHAT IS YOUR DIAGNOSIS? A three year old, male neutered miniature schnauzer was presented to the R(D)SVS Internal Medicine Service for investigation of a two month history of progressive dysuria and stranguria. On physical examination he was bright. The heart rate was 80 beats per minute with strong synchronous peripheral pulses and a normal chest auscultation. Respiratory rate was 16 breaths per minute. The oral mucous membranes were pink and moist, with a capillary refill time of less than two seconds. The penis examination was unremarkable. Abdominal palpation was unremarkable, peripheral lymph nodes were within normal limits and rectal temperature was 38.0⁰C. Rectal examination was unremarkable. 1) What are the differential diagnoses for this case? 2) How would you investigate this case further? 1) Differentials diagnoses would include: 1. 2. 3. 4. 5. 6. Urinary tract infection. Urolithiasis (e.g. Calcium Oxalate, Struvite, Urate or compound more likely). Inflammatory cystitis or urethritis. Trauma. Prostatic disease. Urinary tract neoplasia less likely. 2) How would you investigate this case further? Initial diagnostic work-up included haematology, serum biochemistry and urinalysis. Test Result Reference range WBC 12.3 6 - 15 x10e9/l Neutrophils 7.48 3.6 - 12 x10e9/l Lymphocytes 3.0 0.7 - 4.8 x10e9/l Monocytes 0.78 0 - 1.5 x10e9/l Eosinophils 0.8 0 - 1 x10e9/l 0 0 - 0.2 x10e9/l RBC 4.1 5.5 - 8.5 x10e12/l PCV 0.30 0.39 - 0.55 l/l Hb 11.2 12 - 18 g/dl MCV 50 60 - 77 fl MCHC 34.5 32 - 36 % Platelets 365 200 - 500 x10e9/l Reticulocytes 25 <60 x10e9/l Basophils Test Albumin ALT ALKP Bile Acids Bilirubin (total) Calcium (ionised) Chloride Cholesterol Creatinine Globulin Inorganic Phosphate Potassium Protein (total) Sodium Triglyceride Urea (BUN) Glucose Result 23 255 190 17 3.1 1.34 100 3.1 109 29.2 1.91 4.2 51 158 0.7 1 2.7 Reference range 26 - 35 g/l 21 - 102 U/l 20 - 60 U/l 0 - 7 umol/l 0 - 6.8 umol/l 1.15 - 1.54 mmol/l 99 - 115 mmol/l 3.8 - 7 mmol/l 40 - 132 umol/l 18 - 37 g/l 0.9 - 2 mmol/l 3.6 - 5.6 mmol/l 58 - 73 g/l 139 - 154 mmol/l 0.57 - 1.14 mmol/l 1.7 - 7.4 mmol/l 3 - 5 mmol/l Table 2: Serum biochemistry results. Table 1: Haematology results. Test Result USG 1.012 pH 7.0 Blood 1+ Protein Negative Nitrite Negative Ketones Negative Glucose Negative Table 3: Urinalysis results. Leukocytes Negative Bilirubin Negative Sediment (See Figure 1) Table 3: Urinalysis results. Figure 1: Fresh urine deposit under microscope (40x). The results are suggestive of liver insufficiency, in this case a vascular anomaly such as a portosystemic shunt (PSS) was considered to be the most likely cause. Haematology showed a mild microcytic normochromic non-regenerative anaemia. This is thought to be caused by mechanisms altering the hepatic iron metabolism. Serum biochemistry evidenced mild hypoalbuminaemia, hypocholesterolaemia, hypoglycaemia and low blood urea nitrogen. The low urea may due to decreased hepatic synthesis capacity and a deficient urea cycle. Mildly increased bile acids were also detected. The urinalysis results showed isosthenuria with a low urine specific gravity of 1.012 and ammonium biurate crystalluria (see Figure 1). Ammonium biurate crystals are golden brown and spherical with irregular protrusions, giving a thorny appearance. They may be found in patients with a deficiency in urea and uric acid cycles resulting in excessive renal ammonia and urate excretion. These compounds can precipitate into crystals or stones in the kidney or bladder, a major cause for lower urinary tract signs in these patients. The low specific gravity results from the polydipsia that these animals display, as well as the poor medullary concentration gradient that occurs with low BUN. Further liver function testing was indicated. Measurement of postprandial serum bile acids is the test of choice for evaluating liver function in animals suspected of having a PSS. The result of this were 78 umol/l, a value well above the reference range. An abdominal ultrasound was then performed, showing microhepatia and an extrahepatic portosystemic shunting vessel. Two small urinary stones were evidenced in the bladder (Figure 2). Figure 2: Showing single tortuous vessel shunting from the splenic vein to the vena cava, with and without Doppler (A and B). Two small 2mm uroliths were seen as well in the urinary bladder (arrow in C). Outcome: Medical therapy was started with Metronidazole 7.5mg/kg PO BID, Lactulose 0.5ml/kg PO TID and feeding a liver disease prescription diet. A surgical attenuation of the shunting vessel was performed several weeks after diagnosis, by means of an ameroid constrictor placement. The patient did well and the urinary tract signs resolved after several weeks. Discussion: Congenital extrahepatic portosystemic shunts (EHPSS) are seen most commonly in small or toy breeds such as Yorkshire Terrier, Maltese, Pug or Miniature Schnauzer; while intrahepatic shunts are overrepresented in larger dogs. The three most commonly affected body systems are CNS, GI and urinary system. Signs normally start early in life, including weight loss or failure to gain weight, occasional lethargy or abnormal behaviours (stargazing, head pressing, random barking, aggression, etc.). Then, more obvious neurological signs (ataxia, circling, blindness or seizures), GI signs (vomiting, diarrhoea, melena) or polyuria and polydipsia commonly develop. As in this case, 20-50% of the animals are reported to have signs of lower urinary tract disease: haematuria, stranguria, pollakiuria or urethral obstruction. Formation of ammonium urate calculi is common and can be associated with bacterial urinary tract infections. Any patient showing lower urinary tract signs benefits from a full urine analysis, always including a fresh and stained deposit examination; this allowed us to detect urinary crystals in this particular case. The final diagnosis of EHPSS is made by imaging techniques. Ultrasonography is the most widely used diagnostic tool for PSS detection although other imaging techniques such as Computed Tomographic Angiography can be performed as well. Ultrasonographic diagnosis can be difficult; especially in small patients, with small vessel size, depending on its location or the presence of gas in the GI tract. In practice, abdominal radiographs can be very useful. Often they demonstrate microhepatia and bilateral renomegaly. Marginally radiopaque calculi can be seen in the urinary bladder in cases with ammonium biurate stones. If these are mixed with other salts, they can be more radiopaque. In some patients, the calculi do not resolve with treatment for the PSS or can relapse. In these cases, calculi prevention can be challenging. It usually consists in increasing the water intake or adding water to food aiming for lower USG, urine alkalinisation with substances like potassium citrate or lower purine foods (which may not be ideal for dogs with liver disease in all cases).