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9/17/2013 PSS – PortoSystemic Shunts Introduction z Anomalous connection between the portal and systemic venous systems James Y Kim DVM, DACVS Providing the best quality care and service for the patient, the client, and the referring veterinarian. Introduction z Bypass of the liver – – Normal in utero (ductus venosus) Abnormal postpartum z z z Patent ductus venosus Intrahepatic Extrahepatic – – Single Multiple Portal vein hypoplasia – Microvascular dysplasia z z Abnormal hepatic bloodflow Histopathologic finding – z z Communication between portal & systemic circulation at microvascular level Occur concurrently w/ PSS – z z Small intrahepatic portal vessels 58% of dogs & 87% of cats PVH-MVD alone have similar signs to PSS Cairn & Yorkshire Terriers 1 9/17/2013 Liver physiology z Protein metabolism – – z z Albumin Coagulation proteins – Gluconeogenesis Glycogenolysis – – – z – – – Bile acids Cholesterol production Neurologic – z Lethargy, ataxia, obtundation, pacing, circling, blindness, seizures, coma Gastrointestinal – Vomiting, diarrhea, anorexia, pica, melena, hematemesis Extrahepatic – z z z – z – z Small/toy breeds z Vitamins Fats Glycogen Trace minerals Clinical signs z z Kupffer cells Toxic metabolites Bacterial endotoxins Drug metabolism Storage – Fat metabolism – Immune/Clearance – Carbohydrate metabolism – z Signalment Intrahepatic – Yorkies Maltese Havanese Pugs Terriers Large breeds z z z z Irish Wolfhounds Retrievers (labs & goldens) Australian cattle dogs Australian shepherds Cats z DSH, Persians, Siamese, Himalayans, & Burmese Hepatic Encephalopathy (HE) z Urinary – Hematuria, stranguria, pollakiuria, urethral obstruction z z Pathophysiology largely unknown & complex >20 compounds in excess w/ PSS – Ammonia, aromatic AAs, benzodiazepines, GABA, glutamine, short chain FAs, tryptophan z Ammonia – – Excitotoxic ↑glutamate z – Excitatory neurotransmitter Chronicity leads to ↑ to inhibitory factors z z GABA Endogenous benzodiazepines 2 9/17/2013 Diagnostics z Complete blood count – Diagnostics z Microcytosis z – +/- normochromic, nonregenerative anemia – Target cells – Poikilocytes – Leukocytosis Serum chemistry – – – z associated with a poor prognosis Diagnostics z Urinalysis – Hyposthenuria to isosthenuria z z – – Diagnostics z Bile acids – Hepatic encephalopathy (psychogenic PD) Poor renal medullary gradient (decreased BUN) Crystaluria z z – Ammonium biurates Glomerular sclerosis secondary to antigen exposure Paired samples z z – 12 hour fasting 2 hour postprandial Normal values z Proteinuria z Hypoalbuminemia Reduced BUN Hypocholesterolemia Hypoglycemia Fasting 1.7 ± 0.3µM Postprandial 8.3 ± 2.2µM Some normal Maltese dogs have increased serum bile acids 3 9/17/2013 Diagnostics z Baseline Ammonia – z Abnormal in 62-88% of animals w/ PSS Ammonia tolerance test (ATT) – – – Administration of ammonium chloride per os or per rectum Samples taken at prior administration & 30 minutes post Contra-indicated in animals exhibiting HE Imaging Diagnostics z Nuclear Scintigraphy – – – – Great screening tool Highly sensitive Noninvasive, requiring no anesthesia Technetium pertechnetate Protein C z z z z z Vit K dependent serine protease enzyme Test to differentiate PSS from PVH-MVD Normal >70% PSS < 70% PVH-MVD >70% Imaging Diagnostics z Transcolonic scintigraphy – – Isotope infused per rectum into the colon Radioactivity is visualized sooner and in higher concentration at the heart Liver Heart 4 9/17/2013 Imaging Diagnostics z Transplenic scintigraphy – – – Sedation required Ultrasound guided injection Identify location and number of shunts Imaging Diagnostics z Abdominal Ultrasound – – – Highly operator dependent Sensitivity and specificity increases with sedated or anesthetized patients Findings z z Morandi F, Cole RC, Tobias KM, et al. Use of 99mTcO4 transplenic portal scintigraphy for diagnosis of portosystemic shunts in 28 Dogs. Vet Radiol Ultrasound 2005;46:153–161. z z Shunting vessel Microhepatica Renomegaly Cystic calculi Imaging Diagnostics z Computed Tomographic Angiography – – – Gold standard in human medicine Dual-phase CT angiography superior Identify non-surgical PSSs 5 9/17/2013 Other Imaging Diagnostics z Portovenography – – – z z Antibiotics – Treat bacteremia Decrease bacterial ammonia production Metronidazole – Ampicillin – Neomycin – z z z 7.5mg/kg 22mg/kg 22mg/kg MRI – – – 85% in dorsal 91% in right lateral 100% in left lateral Medical treatment – z Performed during laparotomy w/ fluoroscopy Injection into splenic or jejunal vein w/ iohexol Sensitivity z z Other Imaging Diagnostics – Extended anesthesia Cost prohibitive CT provides superior detail CT is extremely quick w/ multi-sliced scanners Medical treatment z Lactulose – – – Convert ammonia (NH3) to ammonium (NH4+) Decrease intestinal transit time 0.5-1.0 ml/kg PO q 6-8hrs 6 9/17/2013 Medical treatment z Gastroprotectants – – – Sucralfate z – Loading 16mg/kg divided over 4 doses during a 12-24hr period Maintenance 2-4mg/kg PO divided into 2-3 doses/day Potassium bromide z Loading 400-600mg/kg divided over 1-5 days Maintenance 20-30mg/kg/day Keppra(levetiracetam) z 40mg/kg Protein-restricted diet 20mg/kg PO q 8hrs Fryer KJ, Levine JM, Peycke LE, Thompson JA, Cohen ND. Incidence of postoperative seizures with and without levetiracetam pretreatment in dogs undergoing portosystemic shunt attenuation. J Vet Intern Med. 2011 NovDec;25(6):1379-84. Medical treatment z Hepatosupport – SAMe – Ursodeoxycholic acid (ursodiol) 18-22% dogs 30-35% cats – Vit E Dairy & vegetable protein sources – Milk thistle (silymarin) Moderate protein restriction z z – z – 2-3µg/kg Medical treatment – z 1.0-2.0mg/kg Misoprostol z Phenobarbital 0.5-1.0mg/kg – z Anti-convulsants – Omeprazole z z z Gastrointestinal ulcerations Famotidine z – Medical treatment z z z z 17-22mg/kg/d 10-15mg/kg/d 15 IU/kg/d 8-20mg/kg divided q 8hrs 7 9/17/2013 Medical treatment outcomes z Long term survival1 – – z z 51.9% for medically treated patients 87.9% for surgically treated patients – – Did not affect survival Intrahepatic vs – Poor prognostic indcators – Age1 – z Predictors of outcome – Extrahepatic2 64.7% vs 33% were euthanized due to uncontrolled signs – 1Greenhalgh SN, Dunning MD, McKinley TJ, Goodfellow MR, Kelman KR, Freitag T, O'Neill EJ, Hall EJ, Watson PJ, Jeffery ND. Comparison of survival after surgical or medical treatment in dogs with a congenital portosystemic shunt. J Am Vet Med Assoc. 2010 Jun 1;236(11):1215-20. 2Watson PJ, Herrtage ME. Medical management of congenital portosystemic shunts in 27 dogs--a retrospective study. J Small Anim Pract. 1998 Feb;39(2):62-8. Surgical treatment z Suture ligation – 2-0 silk Complete attenuation – Partial attenuation – z 86% cannot tolerate Low albumin Anemia Leukocytosis Low body weight (IHPSS) Neurologic signs (HE) Surgical treatment z Ameroid ring – – – Ring of casein surrounded by stainless steel Hygroscopic substance that swells after absorbing fluid Incites fibrous tissue reaction 8 9/17/2013 Surgical treatment z Cellophane banding – – – – Clear nonmedical grade cellophane 1 x 10cm strips folded into thirds Hemoclips used to secure the band Fibrous tissue reaction leading to gradual occlusion Surgical treatment z Surgical video Percutaneous transjugular coil embolization – – – Fluoroscopic guidance Caval stent placed via jugular vein Embolization coils inserted through a vascular catheter Surgical treatment z Liver biopsies – – – Identify PVH-MVD 58% of canine cases 87% of feline cases 9 9/17/2013 Surgical complications z Hypoglycemia – z Portal hypertension – z 44% of cases 2-14% of cases usually w/ suture ligation Seizures – – – 3-18% dogs, 8-22% cats w/in 80hrs post-op Concurrent disease z z Recurrence – – – – Post-operative management z Failure of attenuation Second shunt Development of multiple extrahepatic shunts PVH-MVD Continued medical management – z Antibiotics, lactulose, protein restricted diet Recheck technesium scan – z Recheck bloodwork – – – – @ 3 months Bile acids Albumin BUN @ 6 weeks GME, hypoxia, epilepsy Questions ? Thank you! 10