ASCITES

Dr. Hary Bagijo Sp.PD

Seksi HepatologyGastroenterology
FK UHT/RSAL Dr.Ramelan

ASCITES
DEFINITION FREE FLUID IN THE
ABDOMINAL CAVITY

JAMA 1992;267:2645-2648

Ascites

ascites accumulation of fluid in the abdominal cavity

Whats so bad about

ascites?
Painful
Anorexia & malnutrition
Reduced mobility with
deconditioning
Hernias
Impaired ventilation
with atelectasis &
pneumonia
Increased variceal
pressure
May become infected
(SBP)

Causes of ascites

Cirrhosis
Hepatic congestion (CHF)
Renal disease
Pancreatic
Malignancy
Infections (TB)
Inflammatory disease
Hypothyroidism

Why do cirrhotics
retain salt and
water?

Underfill
Low albumin & portal
HTN
Transudation of fluid
Reduced renal perfusion
Renin release
Salt retention

Serum

Ascites
Hydrostatic

Albumin
Oncotic

Why do cirrhotics retain salt and

water?
Overflow

Systemic vasodilatation
Reduced renal perfusion
Renin, angiotensin system activation
Salt retention
Increased venous pressure
Portal
Systemic

Transudation of fluid

Features of the systemic

hemodynamic derangement of
cirrhosis
Systemic vasodilatation
Low blood pressure
High cardiac output
Mesenteric vasodilatation
Portal hypertension
Pulmonary vasodilatation
Hepatopulmonary
syndrome
Renal vasodilatation
Reduced GFR

Stages of ascites
Salt avidity without ascites
Overt edema/ascites
Responsive to diuretics/salt restriction
Refractory

Hepatorenal syndrome
Type II
Type I

Medical Rx
Salt restriction
Distal tubular
diuretics
Spironolactone
Amiloride

Loop and
proximal
diuretics
Furosemide

Resistant ascites
Inadequate treatment
Patient noncompliance
Physician reluctance

Refractory ascites
Failure to resolve despite maximal diuretics
Intolerance to treatment
Diuretic side effects (cramps, etc.)
Hyponatremia
Prerenal azotemia

Hepatorenal syndrome, type II

Refractory ascites with persistent Cr > 1.5

PATHOPHYSIOLOGY OF ASCITES

HYDROSTATIC PRESSURE
CIRRHOSIS
CHF
CONSTRICTIVE PERICARDITIS

OSMOTIC PRESSURE
NEPHROTIC SYNDROME
MALNUTRITION
PROTEIN LOSING ENTEROPATHY

FLUID PRODUCTION EXCEEDING RESORPTIVE

CAPACITY
INFECTION TB
MALIGNANCY
JAMA 1992;267:2645-2648

HISTORY
USEFUL

H/O INCREASED ABDOMINAL GIRTH

H/O PEDAL EDEMA
H/O WEIGHT GAIN
H/O CHF
H/O HEPATITIS

NOT AS USEFUL

H/O ETOH
H/O MALIGNANCY

JAMA 1992;267:2645-2648

BULGING FLANKS

ASCITES OR OBESITY?
JAMA 1992;267:2645-2648

SHIFTING DULLNESS

METHOD OF EXAMINATION
BEGIN BY PERCUSSING AT THE UMBILICUS AND MOVING TOWARD
THE FLANKS. THE TRANSITION FROM AIR TO FLUID CAN BE
IDENTIFIED WHEN THE PERCUSSION NOTE CHANGES FROM
TYMPANIC TO DULL.
ROLL THE PATIENT ON THEIR SIDE AND PERCUSS AS BEFORE. THE
AREA OF TYMPANY WILL SHIFT TOWARDS THE TOP AND THE AREA OF
DULLNESS TOWARDS THE BOTTOM.
JAMA 1992;267:2645-2648

SHIFTING DULLNESS

PATIENT OR
ASSISTANT
TAP

FEEL

METHOD OF EXAMINATION
HAVE THE PATIENT OR ASSISTANT PLACE
THEIR HANDS IN THE MIDLINE
TAP ONE FLANK SHARPLY AND USE THE
FINGERTIPS OF THE OPPOSITE HAND TO
FEEL FOR AN IMPULSE ON THE OPPOSITE
FLANK
JAMA 1992;267:2645-2648

PUDDLE SIGN

METHOD OF EXAMINATION
PATIENT IS PRONE FOR 3-5 MINUTES AND THEN
RISES TO ALL FOURS
DIAPHRAGM OF THE STETHOSCOPE IS PLACED
OVER MOST DEPENDENT AREA OF THE ABDOMEN
BEGIN BY FLICKING A FINGER OVER A LOCALIZED
FLANK AREA
MOVE THE STETHOSCOPE OVER THE OPPOSITE
FLANK
SUDDEN INCREASE IN INTENSITY IS A POSITIVE
SIGN (NO LONGER USED)
JAMA 1992;267:2645-2648

Causes of ascites

Hepatic (cirrhosis, fibrosis, obstruction)

Renal (nephrotic syndrome, obstrutive, PD)
Cardiac (heart failure, constrictive pericarditis)
Infectious (abscess,TB, Chlamydia, schistosomia)
Gastraointestinal (infarcted bowel perforation)
Neoplastic (lymphoma, neuroblastoma)
Pancreatic (pancreatitis, ruptured pancreatic duct)
GYN (ovarian tumor, torsion, rupture)
Miscellaneous (SLE, VP shunt, chylous, hypothyroidism)

Physical diagnosis

Bulging flanks
Flank dullness
Shifting dullness
Fluid wave
Pedal edema
Puddle sign

Pathophysiologic
mechanisms

Initial therapy
Sodium restriction
Diuretics
Spironolactone 50 400 mg po QD
Furosemide 40 160 mg po BID

Initial therapy
Goal weight loss per day
No edema: 500 grams
Edema: up to 1 kg

Human Serum Albumin:

Properties and
Physiological Function

Human Serum Albumin:

A Unique Protein
Most abundant protein in blood plasma
(accounting for approximately 60% of all
plasma proteins)
Multifunctional protein
Possesses:
unique ligand-binding capacity
enzymatic properties
different types of hydrolytic activity

Serves as a:
transporter
storehouse for several endogenous and exogenous
compounds
Kragh-Hansen U, et al. Biol Pharm Bull. 2002;25:695-705; Peters T Jr. San Diego: Academic Press; 1996.

Human Serum Albumin:

Structure
Albumin is a heart-shaped protein with three spherical domains (IIII), each of which is comprised of 2 subdomains (A and B)

Kragh-Hansen U, et al. Biol Pharm Bull. 2002;25:695-705.

Human Serum Albumin:

Structure
Human serum albumin (HSA) is:
A single-chain protein
A simple protein, thus lacking prosthetic
groups and covalently bound carbohydrate
and lipid
Synthesized and secreted from the liver

Contains 585 amino acids

Molecular mass: 66,500 Da
Kragh-Hansen U, et al. Biol Pharm Bull. 2002;25:695-705; Peters T Jr. San Diego: Academic Press; 1996.

Human Serum Albumin:

Physiological Function
Maintains oncotic pressure difference
between plasma and interstitial space
Involved in the regulation of fluid exchange
across the capillary walls
Ensures distribution of body fluids between
intravascular compartments and body tissues

Negatively charged (overall charge: -15)

The glomerular basement membrane, which
is also negatively charged, cannot filtrate
albumin in urine

Gekle M. Annu Rev Physiol. 20052;67:12-1=12.22.

Human Serum Albumin:

Physiological Function
Serves as a transporter of a variety of
substances, such as

Ca2+
Thyroid and other hormones
Unconjugated bilirubin
Fatty acids
Magnesium
Trytophan
Drugs
Toxins
Toxins are transported to the liver where they are
converted to a water-soluble form that can be excreted

Gekle M. Annu Rev Physiol. 20052;67:12-1=12.22.

Human Serum Albumin:

Physiological Function
Transport properties of albumin are
dependent on:
Its ability to competitively absorb
metabolites at the loading stage
Capacity of the binding site
Strength of ligand fixation during transfer
in blood
Rate of albumin-ligand complex
dissociation, which occurs during
interaction with target objects
MedInnovation GmbH. 2004. Available at: http://www.medinnovation.de/background/hsa.htm.

Human Serum Albumin:

Physiological Function
Properties that allow the many
functions of albumin:
Flexibility of the protein molecule to
change conformation
Readiness/flexibility for
chemical/biological change at binding
sites

MedInnovation GmbH. 2004. Available at: http://www.medinnovation.de/background/hsa.htm.

Human Serum Albumin:

Physiological Function
Buffers pH
Influences renal elimination of
bound small-molecular substances
Binding of these substances to
albumin decreases their filtration rate

Human Serum Albumin:

Normal Values
Although the normal value of human
serum albumin depends on the
laboratory, a level of 3.5 g/dL to 5 g/dL
is generally considered to be normal

Human Serum Albumin:

Transport Malfunctions
Several factors can modify the
conformation/properties of albumin
Modification of the human serum molecule
may be involved in several disease states
Solid tumors preferentially accumulate human
serum albumin

Such modification of the human serum

albumin molecule may have an effect on
organ function and/or disease progression

Human Serum Albumin: What

Causes Low levels of Albumin?
Albumin deficiency may be caused by:
Cirrhosis of the liver (diseased liver is unable to
produce adequate albumin)
Excess excretion by kidneys/bowel (eg, nephrotic
syndrome and protein-losing enteropathy,
respectively)
Shock/trauma (loss of albumin from circulation)
Damaged capillaries and blood vessels, which permit
leakage of albumin from the vascular system (eg, severe
burns)

Malnutrition (or very low-protein diet)

Malabsorption syndromes (eg, Crohns disease,
sprue, Whipples disease)

Adverse Effects of Low Human

Serum Albumin
Loss of oncotic pressure, resulting in
leakage of fluid from the blood vessels
into tissues:
Swelling in the ankles (edema)
Fluid accumulation in the abdomen
(ascites)
Fluid accumulation in the lungs
(pulmonary edema)

Breakdown of the transport system

Reversing Low Albumin Levels:

Indications
Emergency treatment of hypovolemic shock
Burn therapy (during the first 24 hours to
restore volume; beyond 24 hours to maintain
oncotic pressure)
Cardiopulmonary bypass (priming)
Acute liver failure
Sequestration of protein-rich fluids (eg, acute
peritonitis, pancreatitis, mediastinitis,
extensive cellulitis)
Hypoproteinemia, with or without edema (eg,
post-surgery, sepsis, ICU patients)
Bayer Corporation, Pharmaceutical Division. Elkhart, IN; February 2002.

Reversing Low Albumin Levels:

Indications (contd)
Adult respiratory distress syndrome (ARDS)
Neonatal hemolytic disease
Erythrocyte resuspension (to avoid
excessive hypoproteinemia during certain
types of exchange transfusion or with the
use of very large volumes of previously
frozen or washed red blood cells)
Acute nephrosis
Renal dialysis
Bayer Corporation, Pharmaceutical Division. Elkhart, IN; February 2002.

Hemodynamic Effects of a 40-g IV Albumin

Infusion in Patients with Cirrhosis

Increased plasma volume

Decreased systemic vascular resistance
Decreased arterial compliance
Decreased plasma renin and aldosterone

Brinch et al: J Hepatology. 2003;39:24-31.

Albumin in Liver Diseases

Prevalence of liver
disease
Overview of portal
hypertension
Uses of Albumin

Resuscitation
Ascites
Hepatorenal syndrome
Spontaneous Bacterial
Peritonitis

Albumin in Liver Diseases

Prevalence of liver
disease
Overview of portal
hypertension
Uses of albumin

Resuscitation
Ascites
Hepatorenal syndrome
Spontaneous bacterial
peritonitis

Progression of Fibrosis
Liver injury (ie, hepatitis C, hepatitis B, alcohol)
No Fibrosis

Stage 1: Fibrous
expansion of
some portal areas

Stage 3:
Fibrous
expansion of
most portal
areas
with occasional
portal to portal
Courtesy of Gregory Everson, MD.
bridging

Stage 4: Fibrous
expansion of
portal areas with
marked bridging
(portal to portal
and portal to
central)
Stage 5,6: Cirrhosis,
probable or defined

Cirrhotic liver:
Gross anatomy
of cadaver

Portal Hypertension
Portal hypertension
Cirrhosis
Increased intrahepatic
vascular resistance
Decreased nitric oxide
Portal hypertension

Hyperdynamic circulation
Increased splanchnic blood
flow
Increased total blood volume
Increased cardiac output
Systemic vasodilation
(decreased systemic vascular
resistance)
Increased renin-angiotensin,
vasopressin, sympathetic
systems

Albumin in Liver Diseases

Prevalence of liver
disease
Overview of portal
hypertension
Uses of albumin

Resuscitation
Ascites
Hepatorenal syndrome
Spontaneous bacterial
peritonitis

Albumin in Liver Diseases

Prevalence of liver
disease
Overview of portal
hypertension
Uses of albumin

Resuscitation
Ascites
Hepatorenal syndrome
Spontaneous bacterial
peritonitis

Pathophysiology of Ascites

Ascites
Second most frequent complication of
cirrhosis
5-year cumulative rate: 30%

Once ascites develops the 1-year survival is

about 50%
Removal of large amounts of ascitic fluid (>2
liters) should be with concomitant albumin
Prevents circulatory dysfunction (CD)
CD is associated with rapid reaccumulation of
ascites
CD has an increased mortality
Gastroenterology. 1997;113:579.

Hemodynamic Effects of
Albumin in Patients with Cirrhosis
40-g IV albumin infusion in patients with
cirrhosis produces:

Plasma volume
Systemic vascular resistance
Arterial compliance
Plasma renin and aldosterone

J Hepatology. 2003;39:24-31.

Treatment of Moderate-Large
Ascites
Initial
Large-volume
paracentesis + IV albumin
(8 g/L removed)

Maintenance
Low-sodium diet
Spironolactone + loop
diuretics (furosemide)
Large-volume
paracentesis + albumin

American Association for the Study of Liver Disease. 2004.

Albumin in Liver Diseases

Prevalence of liver
disease
Overview of portal
hypertension
Uses of albumin
Resuscitation
Ascites
Hepatorenal syndrome
(HRS)
Spontaneous bacterial
peritonitis (SBP)

Hepatorenal Syndrome (HRS)

End-stage spectrum of ascites; represents the
extreme in systemic vasodilation
Decrease in effective blood volume
Maximal activation of renal vasoconstriction

Definition

Creatinine >1.5 mg/dL in a cirrhotic patient

Exclude other etiologies
Oliguria
Unresponsive to 1.5-L fluid bolus
Proteinuria <500 mg/day

Hepatology. 1996;23:164.

Hepatorenal Syndrome (HRS)

Type I
Progressive renal failure on >2.5 mg/dL in
<2 weeks

Type II
Slow development of renal failure with
creatinine >1.5 mg/dL over months

Gastroenterology. 2001;120:726.

Spontaneous Bacterial Peritonitis

(SBP)
Infection of the ascites without a source,
such as intestinal perforation
Prevalence between 10-30% in cirrhotic
patients
Mortality of 30%
Diagnosis:
PMN cells >250 /mm3 in ascitic fluid

Treatment:
3rd generation cephalosporin for 5 days
PMN=polymorphonuclear
Gastroenterology. 2001;120:726.

Recommendations for the

Treatment of HRS and SBP
Hepatorenal Syndrome (HRS)
Albumin 1 g/kg + vasoactive drug (ie,
octreotide, midodrine or terlipressin)
Liver transplantation

Spontaneous Bacterial Peritonitis (SBP)

IV antibiotics
Albumin 1.5 g/kg within 6 hours of detection
Albumin 1.0 g/kg at day 3 of antibiotic
treatment
American Association for the Study of Liver Disease. 2004.

Diagnostic paracentesis
Indications
New-onset ascites
Admission to hospital
Clinical deterioration
Fever

Contraindications
Virtually none
Fibrinolysis or DIC

Technique
Avoid abdominal scars
Midline if possible
Midline is avascular
Inferior to umbilicus
Risk of entering bladder is low

Lower quadrant approach

Technique
Semirecumbent position is most
common
Dullness at site of needle entry
Ultrasound guidance
Metal needle
1.5 inches
22-gauge for diagnostic paracentesis
16-gauge for therapeutic paracentesis

Technique
Disinfect skin with iodine solution
Local anesthetic for skin and
subcutaneous tissue
Sterile gloves
Drapes not necessary
Z-tract
Do not aspirate continuously

Complications
Prospective study
Low morbidity
No mortality
Abdominal wall hematomas are most
common adverse event

Safe in coagulopathy

Fluid analysis

SAAG
Serum-Ascites Albumin Gradient
= serum albumin ascites albumin
> 1.1 = portal hypertension
< 1.1 = non-portal hypertension

SAAG

SAAG

Large volume
(total)
paracentesis

Can be done as needed to relieve symptoms

Benefits: comfort, nutrition, mobility,
respiratory function, ?renal perfusion
Risks:
Post paracentesis circulatory dysfunction:
prevented with 50 g albumin (transudates only)
Hemorrhage, infection, perforation

Diagnostic paracentesis:
AASLD Practice Guidelines
BA Runyon, 2004. Hepatology 39:841

Abdominal paracentesis should be performed and

ascitic fluid should be obtained from patients with
clinically apparent new onset ascites
Initial lab investigation should include:
Cell count and diff
Total protein, albumin -> calculate SAAG

Other studies can be ordered based on pretest

probability of disease, including:
Culture: routine, AFB, fungal
Chemistry: glucose, LDH, Amylase, TG
Cytology

 Low protein, high SAAG

cirrhotic
High protein, high SAAG
congestive
R sided CHF
Constrictive pericarditis
Budd-Chiari

Paracentesis
as a guide to
diagnosis

Low protein, low SAAG

hypoalbuminemic
Nephrotic
Enteropathic

High protein, low SAAG

exudative

Cancer
TB
Hypothyroid
Pancreatic

Low protein: < 2.5 g/dl

High SAAG: > 1.1 g/dl

Fluid Analysis
Cell Count:
PMNs
Hemorrhagic ascites- corrected PMN

Culture
Usually monomicrobial in SBP

Protein and Albumin

Fluid Analysis
Glucose
Usually falls below in secondary
bacterial peritonitis

LDH- releases from PMN lysis

Increased in SBP; further elevated
in secondary bacterial peritonitis

Amylase
Increased in pancreatitis and gut
perforation

Conclusions
Chronic liver disease (ie, hepatitis B) leads to
development of cirrhosis, which in turn, may
lead to complications
IV albumin should be given in all patients
undergoing large-volume paracentesis
IV albumin + vasopressin analogs may be
effective in the management of HRS
IV albumin + antibiotics are the main therapy
for spontaneous bacterial peritonitis
Paracenteses may be effective to reduce large
ascites