Jaundice and Ascites

Question 1

Jaundice/Icterus

Answer 1

-Yellow pigmentation of skin, sclerae and mucus membranes resulting from elevated serum bilirubin levels
-Typically levels above 3 mg/dL will lead to jaundice, icterus
-Hyperbilirubinemia

-A sign of various illnesses, including liver disease and hematologic disorders

Question 2

The liver has a large reserve capacity of enzymes and thus ______

Answer 2

liver function tests may remain relatively normal until liver dysfunction is severe!!

Question 3

Liver function tests measure

Answer 3

-Aspartate aminotransferase (AST)
(Aka - Serum glutamic oxaloacetic transaminase- SGOT)
-Alanine aminotransferase (ALT)
(Aka - Serum glutamic pyruvic transaminase- SGPT)
-Serum albumin
-Prothrombin time
-Serum bilirubin
-Serum alkaline phosphatase
-Gamma-Glutamyl transferase (GGT)

Question 4

Serum Albumin and Prothrombin time reflect

Answer 4

hepatic capacity for protein synthesis

Question 5

Albumin levels fall with

Answer 5

prolonged liver dysfunction or in acute liver impairment
(Norm: 3.5-5.5 mg/dL)


*If pt has hypoalbuminemia and normal Prothrombin time – Consider malnutrition, renal or GI losses

Question 6

Prothrombin time is dependent on

Answer 6

coagulation factors II, V, VII and X
(2, 5, 7, 10)

-Norm = 10.5 to 13 seconds
-Responds rapidly to altered hepatic function
*However, these are dependent upon Vitamin K and a coexistent vitamin k deficiency must be ruled out.

Question 7

Screening for hepatobiliary disease

Answer 7

Tests of biliary obstruction and cholestasis
Tests of hepatocellular damage

-Important to realize lack of specificity of these tests
-Primary use lies in overall pattern of tests as well as magnitude of abnormality

Question 8

Serum Bilirubin reflects

Answer 8

balance between production, conjugation, and excretion into bile by the liver

-Unconjugated (indirect) and Conjugated (direct)
-Normal = 0.2 – 1 mg/dL
-Conjugated (direct) represents up to 30% of total

Question 9

Serum Alkaline phosphatase
is a group of isoenzymes derived from

Answer 9

Liver, bone, intestine and placenta

Question 10

Elevation of Serum Alkaline phosphatase occurs in a variety of conditions:

Answer 10

-Cholestasis, partial or complete bile duct obstruction
-Bone regeneration
-Pregnancy
-Neoplastic, infiltrative, and granulomatous liver diseases
-An isolated elevated alkaline phosphatase may be the only clue to pathology

Question 11

Aspartate (AST/SGOT) and Alanine (ALT/SGPT) aminotransferases are

Answer 11

Intracellular amino-transferring enzymes in hepatocytes

-After injury or death – these are released into the circulation
-These aminotransferases are sensitive (not specific) for liver damage
-Quantity of enzyme level correlates with the severity of hepatic necrosis

Question 12

ALT

Answer 12

-Found primarily in hepatocytes
***More specific than AST for liver disease***
-In most hepatocellular disorders, ALT is higher than AST
**Except in alcoholic liver disease (where its reversed)

Question 13

AST

Answer 13

-Found primarily in liver and cardiac muscle; but also in skeletal muscle, kidneys, brain, lungs pancreas, leukocytes, erythrocytes
**Will be higher than ALT in alcoholic liver disease
-Usually 2 or 3 times that of ALT

Question 14

GGT

Answer 14

-Increased in any cause of acute damage to the liver or bile ducts
-Not very specific and thus not really part of work-up for acute liver dysfunction/injury
-Can be helpful in determining reason for elevation of Alkaline Phosphatase level in serum (see next slide)

Question 15

If GGT is low or normal, then elevation of Alk Phose is likely due to

Answer 15

bone disease rather than liver injury or insult

-A low level or normal GGT level also makes it less likely that the person has consumed alcohol or has liver disease

Question 16

Most bilirubin (80%) is derived from

Answer 16

the breakdown of senescent red blood cells (RBCs)
-The remainder derives from ineffective erythropoiesis and catabolism of myoglobin and hepatic hemoproteins
-Normal rate of production is about 4 mg/kg body weight daily

Question 17

Bilirubin is detected in biologic fluids by the van den Bergh reaction:

Answer 17

Direct-reacting fraction -> Conjugated bilirubin

Indirect-reacting fraction -> Unconjugated bilirubin

Total minus direct= indirect

Question 18

Causes of Unconjugated Hyperbilirubinemia

Answer 18

-Overproduction
-Impaired hepatic uptake
-Decreased conjugation of bilirubin
**Not usually associated with significant hepatic disease

Question 19

Pre-Hepatic Etiology of Unconjugated Hyperbilirubinemia

Answer 19

1. Any condition that results in excessive bilirubin production
(Hemolysis, Hematomas, Pulmonary emboli-->all things that break down RBCs and make bilirubin)
-Genetic disorders: Glucose-6-phosphate dehydrogenase deficiency, Sickle cell anemia, Spherocytosis

-Infectious diseases (Malaria)

Question 20

Jaundice resulting from hemolysis is usually

(pre hepatic)

Answer 20

mild

-Serum bilirubin levels rarely exceed 5 mg/dL in the absence of coexisting hepatic diseases

Question 21

Hemolysis can be investigated by examining: (pre hepatic)

Answer 21

-Peripheral blood smear (and bone marrow smear)
-Measuring reticulocyte count, haptoglobin, lactate dehydrogenase (LDH), erythrocyte fragility and Coomb’s test

Question 22

Unconjugated hyperbilirubinemia from Hepatic etiology:

Answer 22

-anything causing hepatic injury can cause hepatic jaundice
-Hepatitis (Any causes: Infectious, toxic metabolites, drugs, auto-immune disorders, and liver tumors)
-Gilbert syndrome
-Crigler-Najjar syndrome
-Niemann-Pick disease type C

Question 23

Impaired Hepatic Uptake can cause jaundice and occurs after

Answer 23

administering certain drugs

-Such as Rifampin
-Those involved in treating Gilbert syndrome

Question 24

Impaired conjugation can be due to

Answer 24

-Crigler-Najjar syndrome
-Acquired defects of UDP glucoronyl transferase induced by drugs such as chloramphenicol

Question 25

Two primary causes of neonatal jaundice

Answer 25

**Immature hepatic metabolic pathways are unable to conjugate bilirubin as efficiently and quickly as in adults
OR
-Bilirubin production is increase

Question 26

Increased bilirubin production in neonates leads to

Answer 26

unconjugated hyperbilirubinemia between 2nd and 5th day of life

-Lasts until the 8th day in normal births or 14th day in premies
-Usually harmless and doesn’t require any type of therapy

Question 27

Severe pathologic unconjugated hyperbilirubinemia in neonatal jaundice is usually caused by

Answer 27

hemolysis (due to blood group incompatibility) and defective conjugation

*This is a serious condition which requires immediate attention
-Can lead to severe hyperbilirubinemia which is a risk for permanent neurologic damage (Kernicterus)
**Phototherapy is the treatment of choice (If there is no response to phototherapy – seek another cause of the jaundice)

Question 28

Conjugated Hyperbilirubinemia is associated with

Answer 28

impaired formation or excretion of all components of bile (cholestasis)

1. A defect in the excretion of bilirubin from hepatocytes into bile (intrahepatic cholestasis)
2. A mechanical obstruction to the flow of bile through the bile ducts

Question 29

Impaired hepatic excretion (Intrahepatic cholestasis) during Conjugated Hyperbilirubinemia can be caused by

Answer 29

-many things
-Drugs – can impair canalicular transport
-Destruction of intrahepatic bile ducts (Primary biliary cirrhosis)

Question 30

Primary biliary cirrhosis

Answer 30

-Chronic, progressive liver disease
-Occurs primarily in women
-Destroys small lobular bile ducts
-Leads to progressive cholestasis
-> portal inflammation -> fibrosis -> cirrhosis

Question 31

Drug-induced cholestasis (Intrahepatic cholestasis) during Conjugated Hyperbilirubinemia can be caused by

Answer 31

A wide array of drugs
-Nitrofurantoin, oral contraceptives, anabolic steroids
-Erythromycin, cimetidine, chlorpromazine
-Prochlorperazine, imipramine, sulindac, and Penicillins

-Post-operative Jaundice, occurs 1-10 days after surgery, 15% incidence after heart surgery

Question 32

Post-hepatic (Obstructive jaundice) during Conjugated Hyperbilirubinemia can be caused by

Answer 32

partial or complete obstruction of intrahepatic or extrahepatic bile ducts

-Most common causes are:
Gallstones in the common bile duct, Pancreatic head tumors

-Other causes include: Biliary atresia, ductal carcinoma, strictures of the common bile duct
-Pancreatitis, pancreatic pseudocysts, or liver flukes (parasites)

Question 33

Lab tests to order when you suspect jaundice

Answer 33

Comprehensive metabolic panel (CMP) [electrolytes, liver enzymes (including direct and indirect-bilirubin)], lipase, complete blood count


-Also ultrasound, CT scan, MRI, MRCP, ERCP,

Question 34

When you suspect jaundice, always ask yourself...

Answer 34

Is the patient on a medication that can be causing things? chart slide 47

Question 35

Ascites

Answer 35

-Accumulation of excess fluid in the peritoneal cavity
-Liver cirrhosis is the most common cause

Question 36

The ________ has replaced the exudative-transudative classification of ascites

Answer 36

serum ascites-albumin gradient

Question 37

An elevated serum ascites-albumin gradient (>1.1 g/dL) signifies

Answer 37

the presence of portal hypertension

Question 38

Ascites becomes clinically detectable with fluid accumulation of greater than ______

Answer 38

500 mL

**Shifting dullness to percussion is the most sensitive clinical sign of ascites
-Ultrasound is able to detect smaller volumes (250 mL)

Question 39

Ascites Overflow theory

Answer 39

-Overflow of fluid into the peritoneum resulting from portal hypertension and splanchnic vasodilation
-Excess renal sodium
-Water retention

Question 40

Ascites Underflow Theory

Answer 40

-Decreased effective circulating blood volume resulting from systemic arterial vasodilation leading to activation of neurohumoral systems
-Sodium and water retention

Question 41

Intervention is typically done when symptomatic, procedure of choice is

Answer 41

(symptoms are dyspnea, abdominal pain, etc…)

-Paracentesis is procedure of choice
-Usually done under ultrasound
-Can drain as much as 5-8 liters of fluid

Question 42

Ascites with hyponatremia?

Answer 42

restrict dietary sodium AND fluids

Question 43

Ascites with normal serum sodium?

Answer 43

restrict dietary sodium only
(

Question 44

If you have recurrent ascites after sodium restriction, try _________

Answer 44

Diuretic therapy (Spironolactone and Furosemide)

Question 45

Diuretic therapy (Spironolactone and Furosemide) doesn't work and pt has refractory ascites despite max diuretics or pt has electrolyte abnormalities/renal dysfunction try these 3 things:

Answer 45

1. Large volume paracentesis with colloid expansion (IV albumin)

2. Shunt placement (TIPS/surgical shunt)

3. Aquaretics? (class of drug that is used to promote aquaresis, the excretion of water without electrolyte loss, increase urine output and renal blood flow but maintain electrolytes in body)

Question 46

If surgical shunt/paracentesis/aquaretics don;t help ascites

Answer 46

Consider liver transplant