Evaluation of Ascites

Andrew MaclennanMorning Report

July 24, 2009

Pathophysiology of Ascites

From: Robbins Basic Pathology

Causes of AscitesCause Frequency

Cirrhosis 81%

Cancer 10%

Heart Failure 3%

Tuberculosis 2%

Dialysis 1%

Pancreatic Disease 1%

Other 2%

Source: UpToDate

Rare Causes of AscitesCategory

Infectious diseases Amebiasis, Ascariasis, Brucellosis, Chlamydia peritonitis, Complications related to HIV infection, Pelvic inflammatory disease, Pseudomembranous colitis, Salmonellosis, Whipple's disease

Hematologic Amyloidosis, Castleman's syndrome, Extramedullary hematopoiesis, Hemophagocytic syndrome, Histiocytosis X, Leukemia, Lymphoma, Mastocytosis, Multiple myeloma

Miscellaneous Abdominal pregnancy, Crohn's disease, Endometriosis, Gaucher's disease, Lymphangioleiomyomatosis, Myxedema, Nephrotic syndrome, lymphatic tear or ureteral injury. Ovarian hyperstimulation

Imaging

• Ultrasound with Dopplers– Easily confirms ascites– May see nodularity of cirrhosis– Evaluate patency of vasculature– No radiation, contrast

• CT / MRI – Evaluation for malignancy

Tests on Ascitic FluidRoutine Optional Unusual

Cell count and differential Glucose concentration Tuberculosis smear and culture, adenosine deaminase

Albumin concentration LDH concentration Cytology

Total protein concentration Gram stain Triglyceride concentration

Culture in blood culture bottles

Amylase concentration Bilirubin concentration

Cell Count, differential and culture

• Is ascites infected?– Greater than 250 PMN = SBP

• If ascites is bloody ( > 50,000 RBC/mm3), correct by subtracting 1 PMN / 250 RBC

• Is ascites bloody?– 5% of pts w/ cirrhosis - spontaneous or s/p traumatic

tap. • Non-traumatic associated with malignancy

– 20% of malignant ascites– 10% of peritoneal carcinomatosis

Serum to Ascites Albumin Gradient

• Is portal hypertension present? • 97% accurate

SAAG > 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 GradientSAAG > 1.1 g/dL SAAG < 1.1 g/dL

Cirrhosis Peritoneal carcinomatosis

Alcoholic hepatitis Peritoneal tuberculosis

CHF Pancreatitis

Massive hepatic metastases Serositis

Budd Chiari Syndrome Nephrotic syndrome

Congestive heart failure/constrictive pericarditis

Total Protein

• Exudate ( > 2.5 g/dL) or Transudate?– Supplanted by SAAG

• Is there gut perforation? (vs SBP)– Total protein >1 g/dL – Glucose <50 mg/dL (2.8 mmol/L) – LDH greater than serum ULN

Glucose and LDH

• Consistent 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 ascites• Approaches 1.0 in SBP• >1.0, usually infection or tumor

Other tests• Amylase

– Uncomplicated cirrhotic ascites • About 40 IU/L. The AF/S ratio is about 0.4

– Pancreatic ascites• About 2000 IU/L. The AF/S ratio is about 6

• Triglycerides — run on milky fluid. – Chylous ascites - TG > 200 mg/dL, usually 1000

mg/dL

• Bilirubin — run on brown ascites. – Biliary perforation – AF Bili > serum Bili

Tests for TB

• Smear – extremely insensitive• Culture – 62-83% when large volumes

cultured• Cell count – mononuclear cell predominance• Adenosine deaminase –

– Enzyme involved in lymphoid maturation– Falsely low in pts with both cirrhosis and TB

Cytology

• “almost 100%” with peritoneal carcinomatosis have positive cytology

• Malignant ascites from massive hepatic mets, HCC, lymphoma are usually negative

• Overall sensitivity for detection of malignancy-related ascites is 58 to 75 %

Not helpful

• “Some tests of ascitic fluid appear to be useless. These include pH, lactate, and ‘humoral tests of malignancy’ such as fibronectin, cholesterol, and many others”

Biopsy

Cirrhosis Fatty Liver

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

Causes of Cirrhosis Cause Testing

Alcoholic liver disease History, AST / ALT > 2

Chronic hepatitis C Hep C Ab, Viral load

Primary biliary cirrhosis Antimitochondrial antibodies

Primary sclerosing cholangitis Contrast cholangiography , ANA, Anti smooth muscle Ab, ANCA

Autoimmune hepatitis Type 1: ANA, ANCA antismooth muscle Ab Type 2: anti-LKM-1

Chronic hepatitis B Hepatitis B serologies

Hemochromatosis Ferritin, genetic testing

Wilson’s disease Ceruloplasmin

Alpha-1-antitrypsin deficiency Serum AAT

Nonalcoholic fatty liver disease Hx of DM or metabolic syndrome

Malignant Ascites

• Definition: abnormal accumulation of fluid in the peritoneal cavity as a consequence of cancer.

• Commonly caused by cancers of:– Breast, bronchus, ovary, stomach, pancreas, colon

• 20% of cases have tumors of unknown primary

• Survival poor – usually less than 3 monthsBecker, G. Malignant ascites: Systematic review and guideline for treatment. European Journal of Cancer 42 (2006) 589 - 597

Malignant Ascites: Pathophysiology

• Obstruction of lymphatics by tumor– Prevents absorption of fluid and protein

• Alteration in vascular permeability– Hormonal mechanisms (VEGF, IL2, TNF alpha)

• Decreased circulating blood volume– Activates 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 Ascites

http://www.fresenius.de/internet/fag/com/faginpub.nsf/Content/Pressemappe+ASCO+2007

Management of Malignant Ascites

• Therapeutic paracentesis– Removing up to 5L appears safe – No good data on role of volume expanders

• Diuretics– Equivocal evidence of efficacy– May be helpful for portal HTN– Less/minimally useful when no portal HTN

• Drainage Catheters• Peritoneovenous shunts

Peritoneovenous Shunt

Denver Shunt(Similar to LaVeen Shunt)

Contraindications•Protein > 4.5 g/l (occlusion)•Loculated ascites•Coagulopathy•Advanced renal/cardiac disease•GI malignancy

Complications•Infection•Hematogenous spread of mets•DIC•Pulmonary edema•Pulmonary emboli

Transjugular intrahepatic portosystemic shunt (TIPS)

References1. Up to Date2. Ascites and renal dysfunction in liver disease, Second edition. Edited by Pere Ginès,

Vicente Arroyo, Juan Rodés, and Robert W. Schrier. Malden, Mass., Blackwell, 2005.

3. 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.

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

5. Aslam, N. Malignant ascites; New concepts in pathophysiology, diagnosis, and management. Arch Intern Med. Vol 161. Dec 10/24, 2001.

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