Evaluation of AscitesAndrew MaclennanMorning Report July 24, 2009

Pathophysiology of AscitesFrom: Robbins Basic Pathology

Causes of AscitesSource: UpToDate

CauseFrequencyCirrhosis81%Cancer10%Heart Failure3%Tuberculosis2%Dialysis1%Pancreatic Disease1%Other2%

Rare Causes of Ascites

CategoryInfectious diseasesAmebiasis, Ascariasis, Brucellosis, Chlamydia peritonitis, Complications related to HIV infection, Pelvic inflammatory disease, Pseudomembranous colitis, Salmonellosis, Whipple's diseaseHematologicAmyloidosis, Castleman's syndrome, Extramedullary hematopoiesis, Hemophagocytic syndrome, Histiocytosis X, Leukemia, Lymphoma, Mastocytosis, Multiple myelomaMiscellaneousAbdominal pregnancy, Crohn's disease, Endometriosis, Gaucher's disease, Lymphangioleiomyomatosis, Myxedema, Nephrotic syndrome, lymphatic tear or ureteral injury. Ovarian hyperstimulation

ImagingUltrasound with DopplersEasily confirms ascitesMay see nodularity of cirrhosisEvaluate patency of vasculatureNo radiation, contrastCT / MRI Evaluation for malignancy

Tests on Ascitic Fluid

RoutineOptionalUnusualCell count and differentialGlucose concentrationTuberculosis smear and culture, adenosine deaminaseAlbumin concentration LDH concentration Cytology Total protein concentration Gram stain Triglyceride concentration Culture in blood culture bottlesAmylase concentrationBilirubin concentration

Cell Count, differential and cultureIs ascites infected?Greater than 250 PMN = SBPIf ascites is bloody ( > 50,000 RBC/mm3), correct by subtracting 1 PMN / 250 RBCIs ascites bloody?5% of pts w/ cirrhosis - spontaneous or s/p traumatic tap. Non-traumatic associated with malignancy20% of malignant ascites10% of peritoneal carcinomatosis

Serum to Ascites Albumin GradientIs portal hypertension present? 97% accurateSAAG > 1.1 g/dL Portal HTN SAAG < 1.1 g/dL Other causes

The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Runyon BA; Montano AA; Akriviadis EA; Antillon MR; Irving MA; McHutchison Ann Intern Med 1992 Aug 1;117(3):215-20.

Serum to Ascites Albumin Gradient

SAAG > 1.1 g/dLSAAG < 1.1 g/dLCirrhosisPeritoneal carcinomatosis

Alcoholic hepatitisPeritoneal tuberculosisCHFPancreatitis Massive hepatic metastasesSerositis Budd Chiari SyndromeNephrotic syndromeCongestive heart failure/constrictive pericarditis

Total ProteinExudate ( > 2.5 g/dL) or Transudate?Supplanted by SAAG

Is there gut perforation? (vs SBP)Total protein >1 g/dL Glucose

Glucose and LDHConsistent with infection or malignancy?Infection and cancer consume glucoselow

LDH is a larger molecule than glucose, enters ascitic fluid with difficulty.Ascitis/Serum LDH ratio~ 0.4 in cirrhotic ascitesApproaches 1.0 in SBP>1.0, usually infection or tumor

Other testsAmylase Uncomplicated cirrhotic ascites About 40 IU/L. The AF/S ratio is about 0.4Pancreatic ascitesAbout 2000 IU/L. The AF/S ratio is about 6Triglycerides run on milky fluid. Chylous ascites - TG > 200 mg/dL, usually 1000 mg/dLBilirubin run on brown ascites. Biliary perforation AF Bili > serum Bili

Tests for TBSmear extremely insensitiveCulture 62-83% when large volumes culturedCell count mononuclear cell predominanceAdenosine deaminase Enzyme involved in lymphoid maturationFalsely low in pts with both cirrhosis and TB

Cytologyalmost 100% with peritoneal carcinomatosis have positive cytologyMalignant ascites from massive hepatic mets, HCC, lymphoma are usually negativeOverall sensitivity for detection of malignancy-related ascites is 58 to 75 %

Not helpfulSome tests of ascitic fluid appear to be useless. These include pH, lactate, and humoral tests of malignancy such as fibronectin, cholesterol, and many others

BiopsyCirrhosisFatty Liverhttp://library.med.utah.edu/WebPath/LIVEHTML/LIVERIDX.html#2

Causes of Cirrhosis

CauseTestingAlcoholic liver diseaseHistory, AST / ALT > 2Chronic hepatitis C Hep C Ab, Viral loadPrimary biliary cirrhosisAntimitochondrial antibodiesPrimary sclerosing cholangitisContrast cholangiography , ANA, Anti smooth muscle Ab, ANCAAutoimmune hepatitis Type 1: ANA, ANCA antismooth muscle Ab Type 2: anti-LKM-1 Chronic hepatitis BHepatitis B serologiesHemochromatosisFerritin, genetic testingWilsons diseaseCeruloplasminAlpha-1-antitrypsin deficiency Serum AATNonalcoholic fatty liver disease Hx of DM or metabolic syndrome

Malignant AscitesDefinition: abnormal accumulation of fluid in the peritoneal cavity as a consequence of cancer.Commonly caused by cancers of:Breast, bronchus, ovary, stomach, pancreas, colon20% of cases have tumors of unknown primarySurvival poor usually less than 3 months

Becker, G. Malignant ascites: Systematic review and guideline for treatment. European Journal of Cancer 42 (2006) 589 - 597

Malignant Ascites: PathophysiologyObstruction of lymphatics by tumorPrevents absorption of fluid and proteinAlteration in vascular permeabilityHormonal mechanisms (VEGF, IL2, TNF alpha)Decreased circulating blood volumeActivates RAAS leading to Na retention

Becker, G. Malignant ascites: Systematic review and guideline for treatment. European Journal of Cancer 42 (2006) 589 - 597

Pathophysiology of Malignant Asciteshttp://www.fresenius.de/internet/fag/com/faginpub.nsf/Content/Pressemappe+ASCO+2007

Management of Malignant AscitesTherapeutic paracentesisRemoving up to 5L appears safe No good data on role of volume expandersDiureticsEquivocal evidence of efficacyMay be helpful for portal HTNLess/minimally useful when no portal HTNDrainage CathetersPeritoneovenous shunts

Peritoneovenous ShuntDenver Shunt(Similar to LaVeen Shunt)ContraindicationsProtein > 4.5 g/l (occlusion)Loculated ascitesCoagulopathyAdvanced renal/cardiac diseaseGI malignancy

ComplicationsInfectionHematogenous spread of metsDICPulmonary edemaPulmonary emboli

Transjugular intrahepatic portosystemic shunt (TIPS)

ReferencesUp to DateAscites and renal dysfunction in liver disease, Second edition. Edited by Pere Gins, Vicente Arroyo, Juan Rods, and Robert W. Schrier. Malden, Mass., Blackwell, 2005.The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Runyon BA; Montano AA; Akriviadis EA; Antillon MR; Irving MA; McHutchison Ann Intern Med 1992 Aug 1;117(3):215-20. Becker, G. Malignant ascites: Systematic review and guideline for treatment. European Journal of Cancer 42 (2006) 589 - 597Aslam, N. Malignant ascites; New concepts in pathophysiology, diagnosis, and management. Arch Intern Med. Vol 161. Dec 10/24, 2001.