Transcript JAUNDICE AND ASCITES

JAUNDICE AND ASCITES
An Approach to the Patient with
Suspected Liver Disease
Objectives:
 1. discuss the pathophysiology of
jaundice and ascites
 2. do a complete history and physical
examination on a patient with liver
disease
 3. know the significance of liverlaboratory tests
 4. evaluate a patient with liver
disease
Hyperbilirubinemia
 1. overproduction of bilirubin
 2. impaired uptake, conjugation, or
excretion of bilirubin
 3. regurgitation of unconjugated or
conjugated bilirubin from damaged
hepatocytes or bile ducts
 Unconjugated hyperbilirubinemia
 Conjugated hyperbilirubinemia
Evaluating a patient with
jaundice
 1. determine whether conjugated or
unconjugated hyperbilirubinemia
 2. determine presence of other
abnormal laboratory tests
 In a patient with jaundice, a careful
history, physical examination, and
review of standard laboratory tests
should permit a physician to make an
accurate diagnosis in 85% of cases.
Franz Ingelfinger, MD
1958
Causes of Jaundice
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viral hepatitis
alcohol-induced liver disease
chronic active liver disease
drug-induced liver disease
gallstones and their complications
carcinoma of the pancreas
primary biliary cirrhosis
sclerosing cholangitis
Clinical History
 Related to viral hepatitis
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Blood transfusions
IV drug use
Sexual practices
Contact with jaundiced persons
Needle stick exposure
Work in renal dialysis unit
Body piercing/tattoos
Travel to endemic areas
Clinical History
 Medication related
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Review all prescription medications
Over-the-counter drugs
Use of vitamins, especially vit A
Herbal preparations
Food supplements
Home remedies purchased in health food
store
Clinical History
 Alcohol use
 Detailed quantitative history of both
recent and previous alcohol from patient
and family members
 History of withdrawal symptoms
 CAGE criteria
 Evidence of alcohol associated illnesses
(pancreatitis, perpheral neuropathy)
Quantification of alcohol intake
 1 oz whiskey contains 10-11 g alcohol
 1 12-oz beer contains 10-11 g alcohol
 4 oz red wine contains 10-11g alcohol
 Ingestion of >3 units/day everyday or 21
units/week every week is excessive.
 Threshold for alcohol-induced hepatic injury
appears to be 30 gm for women and 60 gm
for men if ingested >10 yrs
CAGE criteria
 1. has the patient tried to cut back on
alcohol use?
 2. does the patient become angry
when asked about his alcohol intake?
 3.does the patient feel guilty about
his alcohol use?
 4. does the patient need an eye
opener in the morning?
Clinical History
 Miscellaneous
Pruritus
Evolution of jaundice
Recent changes in menstrual cycle
History of anemia
Symptoms of biliary tract disease
Family history of liver disease,
gallbladder disease
 Occupational history
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Physical Examination
 General inspection
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Scleral icterus
Pallor
Wasting
Needle tracks
Skin excoriations
Ecchymosis/petechiae
Muscle tenderness and weakness
Lymphadenopathy
Evidence of congestive heart failure
Physical Examination
 Peripheral stigmata of liver disease
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Spider angiomata
Palmar erythema
Gynecomastia
Dupuytren’s contracture
Parotid enlargement
Testicular atrophy
Paucity of axillary and pubic hair
Physical Examination
 Abdominal examination
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Hepatomegaly
Splenomegaly
Ascites
Prominent abdominal collateral veins
Bruits and rubs
Abdominal masses
Palpable gallbadder
Liver
 Liver span is about 10-12 cm in men, and
8-11 cm in women
 Normal liver is non-tender, sharp-edged,
smooth and not hard, left lobe not palpable
 Modest hepatomegaly in viral hepatitis,
chronic hepatitis, cirrhosis
 Marked enlargement in tumors, fatty liver,
severe congestive heart failure
 Pulsatile liver in tricuspid regurgitation
Spleen
 Normally not palpable
 Enlarged in portal hypertension
because of cirrhosis
 Splenomegaly also seen in infections,
leukemias, lymphomas, infiltrative
disorders, hemolytic disorders, etc
Gallbladder
 Not normally palpable
 Palpable in 25% of cancer of the head of
the pancreas (Courvoisier’s law)
 Palpable in about 30% of cholecystitis,
usually because of stone impacted in neck
of gallbladder
 Palpable in the RUQ at the angle formed by
the lateral border of the rectus abdominis
muscle and the right costal margin
Ascites
 Assessed on physical examination by:
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Shifting dullness
Fluid wave
Puddle sign
Bulging flanks
 Both shifting dullness and fluid wave
test will not uniformly detect fluid less
than 1000 ml
 Both tests have a sensitivity of about
60% when compared with ultrasound
 Confirmation of presence of ascites
by imaging procedures
 Tests can be spuriously positive in
obese patients
Causes of ascites:
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cirrhosis
congestive heart failure
nephrosis
disseminated carcinomatosis
Laboratory findings
 Because many of the clinical features
of liver injury are non-specific, the
history and physical examination are
routinely supplemented by “liver
function” tests, which are so widely
available that they have become a
standard and esssential component of
the evaluation.
Biochemical Liver Tests
 Hepatocellular Necrosis
Aminotransferases
Lactic Dehydrogenase
 Cholestasis
Alkaline Phosphatase
Gamma Glutamyl Transpeptidase
Bilirubin
 Hepatic Synthetic Activity
Prothrombin time
Albumin
Aminotransferases
 Increased levels results from leakage
from damaged tissues, released from
damaged hepatocytes following injury
or death
 AST not exclusive for liver, also found
in heart, muscle, kidney, brain,
pancreas and erythrocytes.
 Confirm liver injury by doing ALT
which is almost exclusive to liver
Aminotransferases
 Acute elevations to >1000 IU reflect
severe hepatic necrosis and usually
seen in viral hepatitis, toxin-induced
hepatitis and hepatic ischemia.
 AST/ALT >2 with AST level of <300IU
is suggestive of alcohol-induced liver
disease.
Higher AST levels in viral hepatitis,
ischemia and other liver injuries.
Aminotransferases
AST and ALT levels
 Poorly correlates with the extent of
hepatocyte injury
 Not predictive of outcome
 Azotemia can lower AST level
 Persistent elevation of AST from
macroenzyme complex with albumin
Etiology of mild ALT/AST
elevations
 ALT predominant
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Chronic hepatitis B & C
Acute hepatitis A & E
Steatosis / steatohepatitis
Medications / toxins
autoimmune hepatitis
 AST predominant
 Alcohol-related liver disease
 Steatosis / steatohepatitis
 cirrhosis
Etiology of mild ALT/AST
elevations
 Nonhepatic
 Hemolysis
 Myopathy
 Thyroid disease
 Strenuous exercise
Time Course of ALT
5000
Ischemia/Toxin
Viral/Drug
ALT
(U/L)
1000
0 Weeks
1
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4
Lactic Dehydrogenase (LDH)
 Wide tissue distribution
 Massive but transient elevation in
ischemic hepatitis
 Sustained elevation with elevated
alkaline phosphatase in malignant
infiltration of the liver
Alkaline Phosphatase
 Major sources: bone and liver
 Others: intestine, placenta, adrenal
cortex, kidney and lung
 Increased levels because of increased
synthesis and release from damaged
cells
 Marked increase in infiltrative hepatic
disorders or biliary obstruction
Alkaline Phosphatase
 Marked increases seen in ductular
injury – intrahepatic cholestasis,
infiltrative process, extrahepatic
biliary obstruction, biliary cirrhosis,
malignancy and organ rejection
 Lesser increase in viral hepatitis,
cirrhosis and congestive hepatopathy
Gamma Glutamyl Transpeptidase (GGTP)
 Wide distribution
 Not found in bone
 Main use: determine if elevation in AP is
liver rather than bone in origin
 Induced by alcohol and drugs
 GGTP/AP ratio > 2 suggests alcohol abuse
 Isolated elevations are non-specific, most
cases not associated with clinically
significant liver disease
5 ‘ Nucleotidase
 Wide distribution
 Significant elevations in liver disease
 Sensitivity comparable to AP
detecting obstruction, infiltration,
cholestasis
Measurement of serum bilirubin
(van den Bergh reaction)
 Direct fraction = conjugated bilirubin = B1
- fraction that reacts with diazotized sulfanilic
acid in the absence of an accelerator
 Total bilirubin
- amount that reacts with diazotized sulfanilic
acid in the presence of an accelerator
 Indirect fraction = unconjugated bilirubin = B2
- the difference between total and direct
fraction
Normal serum bilirubin
 Total bilirubin
3.4-15.4 uml
0.2-1 mg/dL
 Direct bilirubin
5.1 uml
0.3 mg/dL
Bilirubin
 Serum bilirubin level normally almost
unconjugated
 Bilirubin in urine is conjugated thus
indicative of hepatobiliary disease
 In chronic hemolysis with normal liver, levels
usually not more than 5 mg/dl
 Magnitude of elevation useful prognostically
in alcoholic hepatitis and acute liver failure
Urine bilirubin
 Bilirubin found in the urine is
conjugated bilirubin
 Unconjugated bilirubin is bound to
albumin in the serum; it is not filtered
by the kidney; and is not found in the
urine
Prothrombin Time
 Most important predictor of outcome in
acute liver failure
 Useful in monitoring hepatic synthetic
function
 Useful indicator of liver failure in both
acute and chronic hepatic injury
provided that cholestasis with
malabsorption of Vit K has been
excluded
Albumin
 Half life of 20 days
 Less useful than prothrombin time in
monitoring acute liver disease
because of long half life
 Correlates with prognosis in chronic
liver disease- used for grading system
Characteristic Biochemical
Patterns:
HEPATOCELLULAR NECROSIS
Toxin/Ischemia
Viral
Hepatitis
Alcohol
Aminotransferases 50-100x
5-50x
2-5x
AP
1-3x
1-3x
1-10x
Bilirubin
1-5x
1-30x
1-30x
Prothrombin
time
Prolonged & unresponsive to Vitamin
K in severe disease
Albumin
Decreased in subacute/chronic
disease
Characteristic Biochemical
Patterns:
BILIARY OBSTRUCTION
Complete
Partial
Pancreatic CA Hilar tumor,
PSC
Aminotransferases
AP
Bilirubin
Prothrombin
time
Albumin
1-5x
2-20x
1-30x
1-5x
2-20x
1-5x
Often prolonged & responsive
to parenteral vitamin K
Usually normal, decreased in
advanced disease
Characteristic Biochemical
Patterns:
HEPATIC INFILTRATION
Aminotransferases
AP
Bilirubin
Prothrombin time
Albumin
1-3x
1-20x
1-5x (often normal)
Usually normal
Usually normal
History & PE
Laboratory tests
Isolated elevation
Of bilirubin
Bilirubin & other
Liver tests elevated
Isolated elevation of bilirubin
Indirect hyperbilirubinemia
(Direct < 15%)
Drugs: Rifampicin
Probenecid
Inherited disorders:
Gilbert’s syndrome
Hemolytic disorders
Ineffective erythropoieisis
Direct hyperbilirubinemia
(Direct > 15%)
Inherited disorders:
Dubin-Johnson syndrome
Rotor’s syndrome
Bilirubin & other liver tests
elevated
Hepatocellular pattern:
ALT/AST elevated out
of proportion to
alkaline phosphatase
Cholestatic pattern:
Alkaline phosphatase
out of proportion
ALT/AST
Hepatocellular pattern
1. Viral serologies
Hepatitis A IgM
Hepatitis B surface
antigen & core antibody
Hepatitis C RNA
2. Toxicology screen
Acetaminophen level
3. Ceruloplasmin (if patient less
than 40 yrs of age)
4. ANA, SMA, LKM, SPEP
Results (-)
Additional virologic testing:
CMV DNA, EBV capsid antigen
Hepa D antibody (if indicated)
Hepa E IgM (if indicated)
Liver biopsy
Results (-)
Cholestatic pattern
Ultrasound
Dilated ducts
Extrahepatic cholestasis
CT/ERCP
Ducts not dilated
Intrahepatic cholestasis
Serologic testing:
AMA
Hepatitis serologies
Hepatitis A, CMV, EBV
Review drugs
Results (-)
ERCP/ Liver biopsy
AMA (+)
Liver biopsy