2. Diseases of the
Liver & Biliary System

3. • If individual hepatocytes are destroyed
but the architecture of the lobule is not
destroyed, the remaining hepatocytes will
totally regenerate the liver parenchyma.
Liver regeneration

4. • If whole lobules are destroyed, the
remaining lobules will expand. They will
function normally, though bile may not
be drained quite so well.

5. • Of course, if scar tissue alters the flow of
blood through the liver (i.e., cirrhosis has
occurred), regeneration will only produce
less-than-fully-perfused nodules of liver
cells.
– (This will disappoint well-read problem drinkers who
understood that their hepatocytes had unlimited
capacity to regenerate....)

8. NORMAL CT SCAN

9. • Blood enters the liver from the hepatic artery
and the portal vein and leaves the liver from
the hepatic vein.
• The blood from the artery carries oxygen while
the portal vein carries nutrients from the
intestine.
Liver blood supply

11. • The portal vein is formed by the junction of the
splenic & superior mesenteric veins.
• Within the liver, the hepatic artery & portal vein
come together with the bile ducts & lymphatics.
• The branches of all of these vessels extend into
the liver into the central lobular vein
Functional anatomy

12. • The acinus make up the primary functional unit
of the portal tract which contains branches of the
hepatic artery, bile ducts, branches of the portal
vein.
• Hepatocytes (liver cells) are in the ascini. They
contain glycogen. Each cell abuts the sinusoids.
• The bile canaliculi run between the liver cells
forming a network which end up in the bile ducts.
Functional anatomy

14. • Inside the two lobes is a network of tubes, also
called the biliary tree that carries bile from the
liver to the intestine.
• Bile is a substance that helps carry away wastes
and is needed for the breakdown and absorption
of dietary fats.
Hepatic Ducts

15. • Each tube is called a duct. Smaller ducts
connect to larger ducts. The larger ducts
join to form the hepatic duct.
• This duct network allows bile to drain out
of the liver.

16. • Concentrate & conduct the 1-1.5L of bile
produced by the liver to the intestine
• Fasting diversion of bile into the gall bladder
for storage & concentration
• Food intake releases CCK to relax sphincter of
Oddi for delivery of bile into the intestine
Gallbladder

17. • Bile acids & detergents cholesterol &
phospholipids to the intestine.
• Also solubilizes dietary fat & promotes its
digestion & absorption

22. The liver has multiple functions:
• Making bile to help digest foods
– Bile acid synthesis & secretion
• Stopping cuts from bleeding (coagulation)
– Responsible for the synthesis of prothrombin,
factor VII, IX, and X from vitamin K absorption.
What Does the Liver Do?

23. • Killing germs, helping keep the body
healthy
• Filtering toxic chemicals from the body
– Remove waste products of nutrient breakdown
• Biotransformation, detoxification & excretion of
various endogenous & exogenous compounds

24. • Helps with disposing of bilirubin
– excretes bilirubin into the small bowel so that
bowel bacteria can change it into the safe green
colored biliverdin.
– Break down the major nutrients in foods
(protein, fats and carbohydrates)
Role of Liver (cont)

25. • Helping to build muscles/ proteins
• Plasma protein synthesis
• Lipid & lipoprotein synthesis
• Glucose homeostasis

26. • Albumin is synthesized exclusively in the liver
• albumin is essential for carrying molecules (and
drugs), and for keeping fluid in the blood vessels.
• Hypoalbuminemia causes fluid shift into tissue
and patient will show signs of edema.
• albumin decreases in malabsorption & tumor
necrosis, or any form of chronic liver disease.
Role of the liver (cont)

27. • Storing energy
– Store vitamins A, D, E and K, & B12
Role of the liver (cont)
Fate – Soluble Vitamins
Vitamin Function
A Visual pigments, normal development of bones
D Absorption of Ca++
E Antioxidant, stability of cell membranes
K Prothrombin synthesis (clotting)

28. • Bilirubin is the primary waste product of
heme metabolism -degradation of
hemoglobin (RBC’s).
• Unconjugated bilirubin is transported in the
plasma bound to albumin.
• The liver is the major site of metabolism of
bilirubin & ammonia
Liver Physiology

29. • The metabolism of carbohydrate in the liver
is regulated by insulin, glycogen,
catecholamines, corticosteroids, & thyroxine
• Most drugs are metabolized by the liver,
microsomal enzymes such as cytochrome
p450 system and rendered water soluble
Hepatic Physiology (cont.)

34. • Liver Function
• Hepatic Test
• Jaundice
• Biliary Tract Disease
– Cholelithiasis-Choledocholithiasis
– Cholecystitis-Cholangitis
– Biliary tract obstruction
Disorders

35. • Hepatic Disease
– Hepatitis Acute & Chronic A/B/C/D/E,
ETOH/drug
– Cirrhosis
– Hepatic Failure
• Neoplasm (later section)

37. Functions of the Liver and
Manifestations of Altered Function
Function Manifestations of Altered
Function
Production of bile salts Malabsorption of fat and fat-
soluble vitamins
Elimination of bilirubin
Metabolism of steroid hormones
Elevation in serum bilirubin and
jaundice
Sex hormones Disturbances in gonadal function,
including gynecomastia in the
male
Glucocorticoids Signs of increased cortisol levels
(i.e., Cushing’s syndrome)

38. Function Manifestations of Altered Function
Aldosterone Signs of hyperaldosteronism (e.g.,
sodium retention and hypokalemis)
Metabolism of drugs Decreased drug metabolism
Decreased plasma binding of drugs
owing to a decrease in albumin
production
Carbohydrate
metabolism
Hyperglycemia may develop when
glycogenolysis and gluconeogenesis
are impaired
Stores glycogen and
synthesizes glucose
from amino acids, lactic
acid, and glycerol
Abnormal glucose tolerance curve
may occur because of impaired
uptake and release of glucose by the
liver

39. Fat metabolism
Formation of lipoproteins
Conversion of carbohydrates
and proteins to fat
Impaired synthesis of
lipoproteins
Synthesis, recycling, and
elimination of cholesterol
Formation of ketones from
fatty acid
Protein metabolism
Deamination of proteins
Altered cholesterol levels
Formation of urea from
ammonia
Elevated blood ammonia
levels

40. Synthesis of plasma proteins Decreased levels of plasma
proteins, particularly
albumin, which contributes
to edema formation
Synthesis of clotting factors
(fibrinogen, prothrombin,
factors V, VII, IX, X)
Bleeding tendency
Storage of mineral and
vitamins
Signs of deficiency of fat-
soluble and other vitamins
that are stored in the liver
Filtration of blood and
removal of bacteria and
particulate matter by
Kupffer’s cells
Increased exposure of the
body to colon bacilli and
other foreign matter

41. Clinical Manifestations of Liver Disease
Sign/Symptom Pathogenesis Liver Disease
Constitutional
Fatigue, anorexia,
malaise, weight loss
Liver dysfunction Acute or chronic
hepatitis Cirrhosis
Fever Hepatic inflammation
or infection
Liver abscess
Alcoholic hepatitis
Viral hepatitis
Fetor hepaticus Sulfur compounds,
produced by intestinal
bacteria, not cleared
by the liver
Acute or chronic
liver failure

42. Sign/Symptom Pathogenesis Liver Disease
Cutaneous
Spider
telangiectasias,
palmar erythema
Altered estrogen and
androgen metabolism
with altered vascular
physiology
Cirrohsis
Jaundice Diminished bilirubin
excretion
Biliary obstruction
Severe liver disease
Pruritus Uncertain Biliary obstruction
Xanthomas and
xanthelasma
Increased serum
cholesterol
Biliary obstruction /
cholestasis

43. Endocrine
Gynecomastia,
testicular atrophy,
di-minished libido
Altered estrogen
and androgen
metabolism
Cirrohsis
Hypoglycemia Decreased
glycogen stores
and
gluconeogenesis
Acute liver failure
Alcohol binge
with fasting

44. Gastrointestinal
Right upper quandrant
abdominal pain
Liver swelling,
infection
Acute hepatitis
Hepatocellular
carcinoma
Liver congestion (heart
failure)
Acute cholecystitis
Liver abscess
Abdominal swelling Ascites Cirrhosis, portal
hypertension
Gastrointestinal
bleeding
Esophageal
varices
Portal hypertension

45. Hematologic
Decreased red cells,
white cells, and/or
platelets
Hypersplenism Cirrhosis, portal
hypertension
Ecchymoses Decreased synthesis
of clotting factors
Liver failure
Neurologic
Altered sleep pattern
subtle behavioral
changes, somnolence,
confusion, ataxia,
asterixis, obtundation
Hepatic
encephalopathy
Liver failure,
portosystemic
shunting of blood

46. History
• FHx: Hx of jaundice or liver disease.
• Social Hx-Recent travel. Exposure to alcohol,
Exposure to individuals or animals with liver or
parasitic disease. Exposure to alcohol.
Multiple sex partners. IV drug use. Exposure to
alcohol.

47. • General:
– fever & weight loss
• Cutaneous:
– spider angiomas, telangiectasias, palmar
erythema, jaundice, xanthomas & xanthelasma
• Endocrine:
– gynecomastia, testicular atrophy, hypoglycemia
Physical exam

48. • G.I.:
– RUQ pain, abdominal swelling/ascites,
heptosplenomegaly, G.I. Bleed
• Hematological:
– pale skin/mucous membranes, ecchymoses
• Neuro:
– Ataxia, somnolence, confusion, asterixis &
obtundation

55. Ascites

59. Telangiectatic Lesions

60. Xanthelasma

61. Xanthomata on the abdomen

62. Splinter hemorrhages

63. Spider angioma

65. • Serum albumin (or prealbumin levels):
– multipurpose serum protein synthesized in the
liver.
– It is decreased when disease is prolonged
enough to deplete the blood levels.
– Albumin is the protein of the highest
concentration in plasma.
Tests of liver function

66. –Albumin transports many small
molecules in the blood (for
example, bilirubin, calcium,
progesterone, and drugs).
– It is also of prime importance in maintaining
the oncotic pressure of the blood (that is,
keeping the fluid from leaking out into the
tissues).

67. –This is because, unlike small molecules
such as sodium and chloride, the
concentration of albumin in the blood is
much greater than it is in the
extracellular fluid.
–Because albumin is synthesized by the
liver, decreased serum albumin may
result from liver disease.

68. – It can also result from kidney disease, which
allows albumin to escape into the urine.
– Decreased albumin may also be explained by
malnutrition or a low protein diet.
– The normal range is 3.4 to 5.4 g/dL.

69. –Prothrombin time (PT)-
• Prolongation of the PT is one of the most
sensitive prognosticators of severe liver disease.
• Tests capacity for protein synthesis
• It measures the function of the livers clotting
ability of factors I (fibrinogen), II
(prothrombin), V, VII, and X.
Tests of Liver Function

70. • When any of these factors is deficient,
the PT is prolonged.
• Coumadin or vitamin K deficiency impair
the function

71. Plasmalogen

72. • The normal PT range is 11 to 15 seconds
– ("normal" varies somewhat in different labs).
• The normal value for the INR is 1.0
• Also used for oral anticoagulant monitoring
following venous thromboembolism,
myocardial infarction, atrial fibrillation or
rheumatic heart disease
PT (prothrombin time) &
INR (international normalized ratio)

73. • For a person on full anticoagulant therapy,
the PT should be 2 to 3 times the laboratory
"control" value. INR 2.0-3.0
• For oral anticoagulant monitoring for those
with mechanical heart valves: INR 2.5-3.5

77. • Transaminases Aspartate-AST (SGOT) &
Alanine-ALT (SGPT):
LFT’s/Transaminases

78. – AST (SGOT)
• is normally found in a diversity of tissues
including liver, heart, muscle, kidney, and
brain. It is released into serum when any one
of these tissues is damaged.
–For example, its level in serum rises with
heart attacks and with muscle disorders.
• It is therefore not a highly specific indicator
of liver injury.

79. – ALT (SGPT)
• is, by contrast, normally found largely in the
liver.
• This is not to say that it is exclusively located in
liver but that is where it is most concentrated.
• It is released into the bloodstream as the result
of liver injury.
• It therefore serves as a fairly specific indicator
of liver

80. – status.released into the circulation following
hepatocyte injury or death.
• The ratio of AST:ALT can be helpful
– AST:ALT > 2:1 suggesting alcoholic liver
disease
– AST:ALT < 1:1 suggesting viral hepatitis.
AST/ALT

81. – They are sensitive, but non-specific for liver damage.
– Need isoenzymes
– The normal range of values for AST (SGOT) is from
5 to 40 units per liter of serum (the liquid part of the
blood).
– The normal range of values for ALT (SGPT) is from 7
to 56 units per liter of serum.
• Normal range can vary according to a number of factors,
including age and gender.

82. • The highest levels of AST and ALT are found
with disorders that cause the death of numerous
liver cells (extensive hepatic necrosis).
– Although, the precise levels of these enzymes do not
correlate well with the extent of liver damage or the
prognosis
AST/ALT

83. • This occurs in such conditions as acute viral
hepatitis A or B, pronounced liver damage
inflicted by toxins as from an overdose of
acetaminophen (Tylenol), and prolonged
collapse of the circulatory system (shock)
when the liver is deprived of fresh blood
bringing oxygen and nutrients

84. • Derived from liver, intestines, bones & placenta.
• Released causing high levels during
– liver damage, particularly necrosis,
– cholestasis/ bile duct obstruction,
– neoplastic,
– infiltrative & granulomatous liver disease.
• Need isoenzymes
Serum Alkaline Phosphatase-
(Alk Phos)

85. Alk Phos

86. Alk Phos

87. Alk Phos

88.
Property
Examined
Significance of Abnormal
Result
Tests of Hepatic Function (Normal Values)
Serum albumin
(3.5-5.5 mg/dl)
Protein
synthetic
capacity (over
days to weeks)
Decreased synthetic capacity
Protein malnutrition
Increased protein loss (nephritic
syndrome, protein-losing
enteropathy)
Increased extracellular fluid
volume
Prothrombin
time (10.5-13
sec)
Protein
synthetic
capacity (hours
to days)
Decreased synthetic capacity
(especially factors II and VII)
Vitamin K deficiency
Consumptive coagulopathy

89.
Property
Examined
Significance of
Abnormal Result
Screening Tests of Hepatobiliary Disease
Tests of Biliary
Obstruction or
Impaired Bile Flow
Serum bilirubin
(0.2-1.0 mg/dl)
(3.4-17.1 mol/L
Extraction of
bilirubin from blood
conjugation and
excretion into bile
Hemolysis
Diffuse liver disease
Cholestasis
Extrahepatic bi,e
duct obstruction
Congenital disorders
of bilirubin
metabolism

90.
Property
Examined
Significance of
Abnormal Results
Serum alkaline
phosphatase (also 5’-
nucleotidase and γ-
glutamyl
transpeptidase) (56-
176 U/L)
Increased enzyme
synthesis and
release
Bile duct obstruction
Cholestasis
Infiltrative liver
disease (neoplasms,
granulomas)Bone
destruction/remodeling
Pregnancy

91.
Property
Examined
Significance of
Abnormal Results
Tests of
Hepatocellular
Damage
Aspartate
Aminotransferase
(AST, SGOT)
(10-30 U/L)
Release of
intracellular
Enzyme
Hepatocellular
necrosis
Cardiac or skeletal
muscle necrosis
Alanine
aminotransferase
(ALT, SGPT)
(5-30 U/L)
Release of
intracellular
enzyme
Same as AST;
however, more
specific for liver cell
damage

92. Characteristic Patterns of Liver Function Tests
Disorder Bilirubin
Alkaline
Phosphatas
e
Aspartate
Aminotransferas
e
Alanine
Aminotransfera
se
Prothromb
in Time
Albumi
n
Gilbert’s syndrome
(abnormal bilirubin
metabolism)
↑ NL NL NL NL NL
Bile duct
obstruction
(pancreatic cancer)
↑↑↑ ↑↑↑ ↑ ↑ ↑-↑↑ NL
Acute
hepatocellular
damage (toxic, viral
hepatitis)
↑-↑↑↑ ↑-↑↑ ↑↑↑ ↑↑↑ NL-↑↑↑ NL-↓↓
Cirrhosis NL-↑ NL-↑ NL-↑ NL-↑ NL-↑↑ NL-↓↓
NL = normal; ↑ = increased; ↓ = decreased (arrows indicate extent of change; ↑-↑↑↑=slight to large)

93. • Liver biopsy- U/S or CT guided.
– Valuable in the histological differential, diagnosis
& treatment of diffuse or localized parenchymal
disease.
– Generally safe.
– Must check coagulation values and platelets
before procedure secondary to risk of severe
hemorrhage.
LFT’s/ Diagnostic Tests

94. • Serum bilirubin- Balance between bilirubin
production and its conjugation & excretion into
bile by the liver.
• Elevated level is not specific for any etiology of
liver disease
Tests for biliary obstruction/cholestasis
&/or hepatocellular damage

95. – Direct bilirubin (already conjugated by the
liver): elevated in intra- or extra hepatic
obstruction.
– Indirect bilirubin (Unconjugated, insoluble):
elevated when hemolysis releases it from red
blood cells (RBC’s) or in rare genetic
deficiencies in conjugating enzymes.

96. • Jaundice- yellow/green appearance to the skin &
eyes (Icterus) produced by increased serum
bilirubin.
• Usually given in a direct/total relationship
• Normal Bilirubin ranges 0.5 to 1.0 mg/dl.
• Levels >3.0 mg/dl to be clinically jaundiced.
– Newborn period is the exception
Approach to Jaundice

97. • Red cells (Heme) break down forming
biliverdin (bile pigment).
• This is unconjugated (indirect bilirubin).
• It is transported by albumin & is not soluble.
– (No Bilirubin in the urine).
Bilirubin Metabolism

98. • (i.e., Binding Bilirubin ("indirect",
unconjugated) to plasma albumin.)
• The bile pigment is converted to
conjugated (Direct bilirubin) by the Kupffer
cells of the liver.

99. • In the liver, the bilirubin is conjugated
– with UDPglucuronate, making it water-
soluble Bilirubin diglucuronide,
• i.e. ("direct" conjugated bilirubin).
• This is soluble & only shows up in blood &
urine with obstruction in the system.

100. • In the terminal ileum the bilirubin is converted to
stercobilinogen & urobilinogen by natural
bacteria.
• Conjugated bilirubin is excreted into the bile and
passed into the intestine where it is further
metabolised: urobilinogen ->urobilin->
stercobilin, which colors the feces brown.
Bilirubin conjugation

101. • Some is reabsorbed and returned to the
liver.
• Some urobilinogen is found in the urine.
• If excretion of conjugated bilirubin is
hindered, it is excreted by the kidney.

102. A. Normal process of conjugation of bilirubin by the liver, which promotes
excretion through the bile. B. With increased destruction of red blood cells,
large amounts of unconjugated bilirubin are released and the liver is unable to
conjugate all that comes to it. Increased bilirubin in the blood results, which
leads to bilirubinemia and jaundice.

104. • Pre-hepatic jaundice
– Hemolytic disease
• Post hepatic jaundice
– Hepatitis
– Drug induced hepatitis
– Cirrhosis
Bilirubin Metabolism

105. • Notes:
– Obstruction of biliary system prevents
production of urobiligen & stercobilinogen
• Stool is light and urine is dark showing
bilirubin

106. • Diseases that elevate blood levels of bilirubin fall
into one of these four categories of disorder:
– 1. Increased bilirubin production
– 2. Decreased bilirubin uptake by the liver
– 3. Impaired conjugation in the liver
– 4. Decreased excretion of bilirubin into the bile
(cholestasis)
Hyperbilirubinemia

107. • The first 3 types listed are unconjugated
(indirect)= normal stool and urine color.
• The 4th
(decreased excretion/ cholestasis)
shows increased conjugated bilirubin (direct)
with dark urine and light stool color.

108. Due to overproduction, decreased hepatic
uptake or decreased conjugation of
bilirubin
Unconjugated (Indirect)
hyperbilirubinemia

109. – 1. Overproduction 20
hemolysis
(autoimmune), ineffective erythropoiesis
(megablastic anemia), increase RBC
fragility/turnover (2,3 DPG deficiency)
– 2. Impaired hepatic uptake: Gilbert’s
syndrome & certain drugs such as rifampin,
anesthetics & radiographic dyes

110. • 3. Impaired conjugation: Hepatocellular
disease, drug inhibition such as
chloramphenicol, anabolic steroids, genetic
disorders such as Gilbert’s syndrome or
Crigler- Najjar syndrome (decreased UDP-
glucuronyl transferases).
Unconjugated (Indirect) hyperbilirubinemia

111. • The most common cause of jaundice is
neonatal jaundice
– They do not have a significant quantity of
glucouronyl transferase (the enzyme used for
conjugation), due to enzyme immaturity, but
kicks in within a few weeks.
Unconjugated (Indirect) hyperbilirubinemia

112. • Bilirubin is very toxic to the neonatal brain
(kernicterus), UV light is used to isomerize
the bilirubin, which prevents it from crossing
the blood-brain barrier.

113. – Common causes of neonatal jaundice Rh
disease/ABO incompatibility is hemolytic
and also impaired hepatic intake.
– Kernicterus: is a type of brain damage that
causes athetoid cerebral palsy and hearing
loss. It also causes problems with vision and
teeth and sometimes can cause mental
retardation.

114. 4. Due to Altered biliary drainage, impaired
hepatic excretion of bile, or extra hepatic
obstructions:
– A. Altered biliary drainage of bile (TPN,
cholestasis, drugs), hepatocellular disease,
cirrhosis.
Conjugated (Direct) hyperbilirubinemia

115. • May occur in setting of cholestasis with
impaired formation or excretion of all
components of bile or hepatocellular injury
independent of cholestasis.
• May indirectly cause increase in unconjugated
also if severe enough
**You will have change in color of stool and urine**

116. – B. Impaired hepatic excretion: intrahepatic
cholestasis- Dubin-Johnson syndrome & all
disorders in the transport of conjugated bile
from the hepatocytes to intrahepatic bile
ducts.
• Drug-induced cholestasis-phenothiazines, OCP’s &
methyltestosterone.
Conjugated (Direct) hyperbilirubinemia

117. – C. Extra hepatic: Gallstones,
pancreatic/biliary obstructive tumors,
strictures & biliary atresia
**Dark brown or green urine implies conjugated
hyperbilirubinemia

118. • Cholestatic jaundice--Increased alk phos to
3-4 times normal.
– Hypercholesterolemia, pruritus, malabsorption of
fat & fat-soluble vitamins.
– Minimal or marked evidence of liver cell damage.
Causes of Conjugated (Direct)
hyperbilirubinemia

119. Determine mechanism involved:
• Hx: pale stools & pruritus--> cholestasis.
– & nausea--> gallstones = biliary obstruction.
– Inquire about drugs & alcohol use, risks for viral
hepatitis & pre-existing liver disease.
Diagnosis of conjugated
hyperbilirubinemia

120. • Laboratory:
– biliary obstruction: <5-10 fold increase in
transaminases & >2-3x normal alk phos.
– Hepatocellular disease: >10-15 fold increase
in transaminases & < 2-3x normal alk phos.

121. • Sepsis-
– mainly gram-negative organisms.
– Mildly elevated serum alk phos
Disorders of the Biliary System

122. • Post-op jaundice-- 1-10 days post-op.
– 15% incidence following heart/ 1% elective
abdominal surgery.
– Increased alk phos & minimally elevated levels of
transaminases.
– Secondary to anesthesia side effects

123. • Hepatocellular disease (hepatitis, cirrhosis)
– elevated transaminases, prolonged PT,
hypoalbuminemia & clinical features of hepatic
dysfunction.
• Extrahepatic biliary obstruction–
– obstruction of extra hepatic bile ducts--gallstones,
neoplasias, bile duct strictures, chronic
pancreatitis.
– Clay-colored stools.

124. • Extra hepatic obstruction: CT or U/S to
determine stone or bile duct dilation.
• Bile duct dilation: endoscopic retrograde
cholangiography (ERCP) for management &
treatment.
• Liver biopsy: for determining cause of
intrahepatic cholestasis.
Special diagnostic procedures in
cholestatic jaundice

125. • "HOT Liver":
Hemolysis
Obstruction
Tumor
Liver disease
Hyperbilirubin Mneumonic

126. Prehepatic (Excessive Red Blood Cell Destruction)
Hemolytic blood transfusion reaction
Hereditary disorders of the red blood cell
Sickle cell anemia
Thalassemia
Spherocytosis
Causes of Jaundice

127. Acquired hemolytic disorders
Hemolytic disease of the newborn
Autoimmune hemolytic anemias

128. Intrahepatic
Decreased bilirubin uptake by the liver
Gilbert’s disease
Decreased conjugation of bilirubin
Hepatocellular liver damage
Hepatitis
Cirrhosis
Cancer of the liver
Drug-induced cholestasis

129. Posthepatic (Obstruction of Bile Flow)
Structural disorders of the bile duct
Cholelithiasis
Congenital atresia of the extrahepatic bile ducts
Bile duct obstruction caused by tumors

130. Predominantly Unconjugated Hyperbilirubinemia
Overproduction
Hemolysis (e.g., spherocytosis, autoimmune disorders)
Ineffective erythropoiesis (e.g., megaloblastic anemias)
Decreased hepatic uptake
Gilbert’s syndrome
Drugs (e.g., rifampin, radiographic contrast agents)
Neonatal jaundice
Classification of Jaundice

131. Decreased conjugation
Gilbert’s syndrome
Crigler-Najjar syndrome types I and II
Neonatal jaundice
Hepatocellular disease
Drug inhibition (e.g., chloramphenicol)

132. Predominantly Conjugated Hyperbilirubinemia
Impaired hepatic excretion
Familial disorders (Dubin-Johnson syndrome, Rotor
syndrome, benign recurrent cholestasis, cholestasis of
pregnancy)
Hepatocellular disease
Drug-induced cholestasis
Primary biliary cirrhosis
Sepsis
Postoperative

133. Extrahepatic (“mechanical”) biliary obstruction
Gallstones
Tumors of the head of the pancreas
Tumors of bile ducts
Tunors of the ampulla of Vater
Biliary strictures (postcholecystectomy, primary
sclerosing cholangitis)
Congenital disorders (biliary atresia)

134. OBSTRUCTIVE JAUNDICE VERSUS
CHOLESTATIC LIVER DISEASE
SUGGESTS
OBSTRUCTIVE
JAUNDICE
SUGGESTS CHOLESTATIC
LIVER DISEASE
History Abdominal pain
Fever, rigors
Prior biliary surgery
Older age
Anorexia, malaise, myalgias,
suggestive of viral prodrome
Known infectious exposure
Receipt of blood products, use
of intravenous drugs
Exposure to known hepatotoxin
Family history of jaundice

135. Physical
examination
High fever
Abdominal
tenderness
Palpable abdominal
mass
Abdominal scar
Ascites
Stigmata of liver disease
(e.g., prominent
abdominal veins,
gynecomastia, spider
angiomata, Kayser-
Fleischer rings)
Asterixis, encephalopathy

136. Laboratory
Studies
Predominant elevation
of serum bilirubin and
alkaline phosphatase
Elevated serum
amylase
Prothrombin time
which is normal or
normalizes with
vitamin K
administration
Predominant elevation of
serum transaminases
Prolonged prothrombin
time which does not
correct with vitamin K
administration
Blood tests indicative of
specific liver disease

138. Approach to the
patient with
cholestatic
jaundice

141. The word "hepatitis" means inflammation of the
liver.
It can be caused by a number of agents, including
bacteria, drugs, toxins and excess alcohol, but of
serious concern is hepatitis that results when any
one of several hepatitis viruses infect the liver.
Hepatitis

143. 1. Virus
A. Hepatitis A (HAV)
B. Hepatitis B (HBV)
C. Hepatitis C (HCV)
D. Hepatitis D (HDV)
E. Hepatitis E (HEV)
F. Cytomegalic (CMV)
G. Epstein-Barr (EBV)
Hepatitis Causes

144. 2. Toxins
3. Alcohol
4. Other diseases
a. Wilson’s disease
b. Leukemia
c. Lymphoma

145. • **Hepatitis E & A are fecal-oral
• (f E c A l –oral)
• **While Hep B,C,D are blood borne
(parenteral)
• “Coming in the Back Door”

146. • Viral Hepatitis
• Hepatitis A virus
• Hepatitis B virus
• Hepatitis C virus
• Hepatitis D virus (“delta agent”)
• Hepatitis E virus
• Epstein-Barr virus

147. • Cytomegalovirus
• Alcohol
• Toxins
• Amanita phalloides mushroom poisoning
• Carbon tetrachloride
• Drugs
• Acetaminophen

148. • Isoniazid
• Halothane
• Chlorpromazine
• Erythromycin
• Other
• Wilson’s disease
• Herbs

149. • Hepatitis A virus
• Hepatitis B virus
• Hepatitis C virus
• Hepatitis E virus
• Yellow fever virus
• Epstein-Barr virus (infectious
mononucleosis)

150. • Lassa, Marburg, and Ebola viruses
• Rubella virus
• Herpes simplex virus
• Cytomegalovirus
• Enteroviruses other than hepatitis A virus
• Leptospires (leptospirosis)
• Entamoeba histolytica (amebic hepatitis)

151. • Hepatitis can be defined as a constellation of
signs & symptoms resulting from inflammation
& hepatic cell necrosis
• In a previously asymptomatic individual the
term “acute” is applied
Acute Hepatitis

152. • Virus is the most common cause of
hepatitis.
– Only occasionally can bacterial infections
like syphilis or TB be considered
• Most cases of acute hepatitis are sub-
clinical & usually undiagnosed

153. • The different types of hepatitis cannot be
distinguished clinically & their distinction
depends upon serological testing
Acute Hepatitis

154. Histologically they are all the same:
• Classically the histological appearance of
acute hepatitis is liver damage & necrosis in
the centrilobular area
• Mild edema occurs in the portal tracts with
some degree of cholestasis causing jaundice,
depending on the degree of obstruction

155. • The hepatic cells undergo degeneration with
some scarring
• Most cases only have minimal damage & go on
to complete recovery
• Some cases progress to liver failure and death
Acute Hepatitis

156. Symptoms of Hepatitis
•Malaise •Vomiting
•Nausea •Diarrhea
•Anorexia •Low grade fever
•Fatigue •Rash
•Arthralgias

157. • Tenderness of the liver
• Hepatomegally on occasion
• Dark urine
• Jaundice
Clinical findings of Hepatitis

158. • Bilirubin elevated
• SGPT (ALT) (very specific for liver)
• SGOT ( AST) (not as specific)
• Alkaline phosphatase (alk phos)
– Nonspecific- represents obstruction of liver
• Can be elevated in bone ds. or child growth
• PT,PTT (elevated c ~55% liver destruction)
• Hypoglycemia
Laboratory Tests (LFT’s)

159. Serum markers for viral hepatitis
Anti-HAV (IgM-IgG) HBsAg
HBeAg Anti-HBc (IgM-IgG)
Anti-HBe Anti-HBs
Anti-HCV Anti-HDV
Monospot, Heterophile
(also do Urinalysis)

160. • 1. Massive hepatic necrosis (1%)
– Usually in B,C,D,E
• 2. Chronic Hepatitis
• 3. Cholestatic Hepatitis Syndrome
– Pruritis
– Dark urine
– Light stools
– Hyperbilirubinemia
– Alk phos elevation
Complications of Hepatitis

161. Don’t complain about the seating arrangements

162. Age: 15-25 yo “ Kissing Disease”
Symptoms:
Fever Hepatosplenomegally
Malaise** Lymphadenopathy*
Loss of appetite Sore throat**
Nausea/Vomiting Rash (maculopapular)
Fatigue Abd pain
Jaundice Headache**
**Most common symptoms
Mononucleosis Epstein-Barr Virus (EBV)

163. • Maculopapular rash:
• NEVER GIVE AMPICILLIN FOR SORE
THROAT TO MONO PATIENT causes
rash
Mononucleosis (EBV)

164. • Key Signs:
– Fever
– Exudative Pharyngitis
– Lymphadenopathy
– Splenomegaly
Mononucleosis (EBV)

165. • Labs
– 1. CBC
• shows a relative lymphocytosis
– Atypical lymphocytes
• Reduction in platelet count
– 2. Mono spot test Heterophile
– 3. EBV specific serology
• IgM specific IgG confirms prior illness
– 4. Transaminase elevated slightly (AST/ALT)
Mononucleosis Epstein-Barr virus

166. • Complications-
– Bacterial pharyngitis
– Upper airway obstruction
– Bells palsy
– Ruptured spleen
Mononucleosis (EBV)

167. • Treatment-
– Supportive therapy
– Tylenol for fever and malaise
– Antibiotic if bacterial pharyngitis is present
• Avoid ampicillin (RASH)
– Steroids for severe pharyngitis & fever
• 40-60 mg of prednisone/day
– Activities reduced- no contact sports for 6 weeks
Mononucleosis (EBV)

168. • Similar to EBV in many ways
• No pharyngitis or respiratory symptoms
• Atypical lymphocytes
• Abnormal liver function studies
• Diagnosis made by CMV titers
• Transmitted in same manner as mono
• more common in transplant and AIDS patients.
**If mono test neg due CMV titer
Cytomegalic Virus

169. • Approximately 25% of all cases of hepatitis
• Less morbidity & mortality
• Contact by fecAl-oral route
• Incubation period 2-6 weeks (shortest)
Hepatitis A

170. • Symptoms: (more severe sx than mono)
Malaise Abd pain
Fever Jaundice
Hepatosplenomegally(25%) Diarrhea
Anorexia
** h/o eating clams, out of country travel, etc.

171. • Duration: 4 weeks
• Complications: rare (no chronic type)
• Lab:
– SGOT , SGPT , Bilirubin ,
– HAV IgM, HAV IgG
• Treatment:
– Good nutrition
– No alcohol
Hepatitis A (cont)

172. • Prophylaxis:
– Administration of Gamaglobulin
• effective in prevention (prior to exposure)
– Post exposure: is recommended for household &
sexual contacts within two weeks, plus Hepatitis A
vaccine
Hepatitis A (cont)

173. – Travelers: recommended in normal dose for
2 mo stay, and triple dose for 4-6 mo stay
– Hepatitis A vaccine given 15 days prior to
travel, followed by 6 mo later

174. • Incubation: 1-6 months
• Symptoms: same as Hep A, but even more
severe
• Contact: Parenteral inoculation, sexual (blood
or mucus membrane)
Hepatitis B

175. • Course:
– 90% recover
– 10% develop chronic hepatitis (with HBsAg carrier
state)
– A small amount go onto chronic progressive hepatitis
which goes on to cirrhosis
– 1% develop a fulminate course
Hepatitis B

176. • Lab tests:
– SGPT (ALT) & SGOT (AST) rise with
symptoms
– Bilirubin & alk phos
– PT, PTT
**(all these labs are higher than in HAV)

177. • Serological tests:
– HBcAg: disappears soon after the peak of ALT
– HBeAg: Positive in acute HBV
– HBsAg: positive in acute & chronic
Hepatitis B
(Lab continued)

178. – Anti-HBs: + in late acute HBV and
immunized (protective)
– HBeAb: appears when antigen decreased
– HBcAb:
• IgM marker for acute infection.
• IgG chronic HBV & carrier

181. • HBsAg: First virologic marker detectable in
serum in acute HBV infection;
• precedes elevations of liver enzymes and clinical
symptoms.
Serologic Markers:

182. • Usually detectable 4 weeks after infection and
typically disappears at 6 months after active
infection.
• Persistence of HBsAg beyond 6 months
implies chronic HBV infection.

183. • Anti-HBs: Appears shortly after HBsAg
disappears from serum and persists indefinitely
in patients who have recovered from acute
infection.
Serologic Markers:

184. • Anti-HBs is felt to be the protective antibody
against HBV infection; thus, vaccine consists
of nonglycosylated HbsAg particles that are
safe and highly immunogenic, thereby
inducing active immunity.

185. • HBcAg: Not detectable in serum
Serologic Markers: (cont)

186. • Anti-HBc:
– IgM
• appears at 1 to 2 weeks after the appearance of
HBsAg;
• its detection in serum is indicative of acute HBV
infection.
• It is the only marker of acute HBV during the
window period between the disappearance of
HBsAg and the appearance of anti-HBs in serum.
Serologic Markers: (cont)

187. • IgM predominates for the first 6 months
following acute infection but may persist
up to 2 years.

188. –IgG
• predominates after 6 months and
generally persists indefinitely in patients
who have recovered from HBV infection.
• Present in virtually all patients who have
ever been exposed to HBV

189. • HBeAg:
– Considered to be a marker of active virus
replication and infectivity;
– also correlates with detection of HBV DNA in
serum.
– Usually appears with or after the appearance of
HBsAg in serum and disappears shortly after peak
elevations in serum aminotransferase activity in
acute infection.

190. – In chronic infection, HBeAg may persist
for years prior to seroconversion to anti-
HBe;
– its presence is indicative of the replicative
stage of HBV infection, which represents a
time of maximal infectivity and liver injury.

191. – Likelihood of perinatal transmission
correlates with presence of HBeAg: ~90%
of HBeAg-positive mothers transmit HBV
to their offspring but only 10-15% of anti-
HBe positive mothers do so.

192. – In a small subset of patients with acute HBV
infection, HBeAg is not detected because of
a viral mutation; in such patients, HBV
DNA levels are elevated, representing the
replicative stage of the virus.

193. • Anti-HBe:
– Appears after seroconversion of HBeAg to anti-HBe.
– Its presence in chronic HBV infection signals the
onset of the nonreplicative phase, where HBV DNA
becomes undetectable in serum and liver injury tends
to subside.
Serologic Markers: (cont)

194. – Generally exists in serum indefinitely unless
seroconversion back to HBeAg occurs.

195. • HBV DNA:
– Probably the most reliable indicator of active viral
replication.
– Can be detected by hybridization methods or PCR.
– Recovery from acute HBV infection is accompanied
by the disappearance of HBV DNA from serum;
however, very low levels may remain detectable by
PCR.
Serologic Markers: (cont)

196. – Persistence of HBV DNA implies chronic
infection.
– Useful in predicting response to interferon
therapy;
• high pretreatment HBV DNA levels > 200
pg/ml by hybridization assay are predictive of
poor response to interferon.
• Also, clearance of HBV DNA is used as an
endpoint in assessing response to treatment.

197. HBs
Ag
Anti-
HBs
Anti-
HBc
HBe
Ag
Anti-
HBe
Interpretation
+ – IgM + –
Acute HBV, high
infectivity
+ – IgG + –
Chronic HBV, high
infectivity
+ – IgG – +
Late-acute or chronic
HBV infection, low
infectivity
+ + + +/– +/–
Heterotypic anti-HBs
with HBsAg; usually
indicates chronic HBV
carrier state

198. HBs
Ag
Anti-
HBs
Anti-
HBc
HBe
Ag
Anti-
HBe
Interpretation
– – IgM +/– +/–
Acute HBV (anti-HBc
window)
– + IgG – +/–
Recovery from HBV
infection
– – IgG – +/–
Low-level HBsAg
carrier or remote past
infection
– + – – –
Immunization for HBV
(HBsAg)

199. • Screening for acute viral hepatitis:
– anti-HAV IgM
– HBsAg
– anti-HBc IgM
– anti-HCV
Screening

200. • Screening for chronic viral hepatitis:
– HBsAg
– anti-HCV
– if + HBsAg then check HBeAg
– +/- HBV DNA.

201. • Chronic hepatitis B is characterized by the
persistent presence of HBV DNA and usually
HBeAg in the serum;
• remissions are characterized by the
disappearance of HBV DNA and HBeAg from
serum despite the persistence of HBsAg.

202. • Treatment:
– After exposure:
• give hepatitis B immunoglobulin (IG) +
• active immunization with HBV vaccine (Combivax) in any
patient who is:
– Stuck by a needle
– Within 14 days of sexual exposure
– An infant born to a mother HBsAg positive
Hepatitis B

203. – Preventative to:
• Health care workers
• Homosexual men
• Household & sexual contacts of HBsAg carriers

204. • Follow up:
– Recheck in 3 months if tests are normal
– A liver biopsy if patient appears to have
chronic hepatitis
– Keep in mind patients with chronic hepatitis B
can develop hepatocellular carcinoma
Hepatitis B

206. • (Blood) Parenteral
– Associated with transfusion in 85% of the time
– inoculation from drug abuse
• 50-70% go onto chronic hepatitis which can lead to
cirrhosis of the liver 20% of the time
• Incubation is 5-10 weeks
• Anti-HCV (antibody to the C virus) is 70% accurate
• Hepatitis C account for 80-90% of the Non A, Non B
hepatitis
Hepatitis C

209. • New serologic test for Hep C
– Anti-HCV if present indicates the presence of viremia
(80%)
– + HCV plus ALT (SGPT) is confirmatory
– A second generation recombinant immunoblot assay
(RIBA) is used for confirmation.
– Polymerase chain reaction (PCR) is used in equivocal
cases, but is not + for at least 6-8 weeks (this is a test to
specifically find the HCV RNA virus)
Hepatitis C

210. • Treatment:
–The patient is given alpha interferon for
the chronic infection 3 x’s/ wk for 6
months
–What is interferon:
• 30% of circulating lymphocytes are B cells
& 70% are T cells
Hepatitis C

211. –B cells produce immunoglobulins that
produce antibodies
–T cells produce cytokines (hormone
like proteins) that bind to the target
cells. There are many kinds, one of
which is interferon which limit viral
replication.

212. • The latest treatment is 6-12 mo of combination
therapy using a-2b interferon plus ribavirin
• The cure rate varies around 40% with no HCV
detectable 6 mo after cessation of treatment
• Do not use if the patient is depressed or on
alcohol (must be off ETOH x 6 mo)
Hepatitis C treatment (cont)

213. • Recommendations:
– Treatment is worth considering on selective
basis on some patients with mild liver disease
– Patients with geno type 2 or 3; treatment is
stopped at 6 mo. Cure rate 50-70% to 90%
– Patients with geno type 1 is less responsive
with overall cure rate of 27%
Hepatitis C

214. • Toxicity:
– Ribavirin can cause hemolytic anemia
– Interferon causes depression

216. • Requires HBV for its replication
• Incubation 4-6 weeks
• Can accelerate chronic hepatitis B to cirrhosis
• Anti-HDV become positive in 12-15 weeks
• Hepatitis B vaccine is preventative
• Treatment poor. Interferon can be tried
**Must have B to get D**
Hepatitis D

217. • Found mostly in India, Asia, Mexico, Africa
• Usually water borne (fEcal- oral)
• Incubation 2-9 weeks
• All cases in US have been imported by
immigrants
• HEV antibodies found in blood
Hepatitis E

218. Comparative Features of the Common
Forms of Viral Hepatitis
Hepatitis A Hepatitis B Hepatitis C
Genome RNA DNA RNA
Incubation
period
3-6 weeks 6 weeks to 6
months
7-8 weeks
Transmission Oral Parenteral Parenteral
Blood No Yes Yes
Feces Yes No No

219. Hepatitis A Hepatitis B Hepatitis C
Vertical No Yes ?
Fulminant
hepatic
necrosis
Very rare Yes Yes
Chronic
hepatitis
No 10% 50%
Carrier state No Yes Yes
Liver cancer No Yes Yes

220. Characteristics of Common Causative
Agents of Acute Viral Hepatitis
Hepatitis
A
Hepatitis
B
Hepatitis
C
Hepatitis
D
Hepatitis
E
Hepatitis
G
Causative
agent
27-nm
RDA
virus
42-nm DNA
virus; core
and surgace
components
Flavivirus-
like RNA
agent
36-nm
hybrid
particle with
HBsAg coat
27-34 nm
non
enveloped
RNA virus
Single strand
RNA virus
Trans
mission
Fecal-oral;
waterborne
or foodborne
Parenteral
inoculation
or
equivalent;
direct
contact
Similar to
HBV
Similar to
HBV
Similar to
HAV
Parenteral

221. Hepatiti
s A
Hepatitis
B
Hepatitis
C
Hepatitis
D
Hepatitis
E
Hepatitis
G
Incubation
period
2-6 wk 4 wk-6 mo 5-10 wk Similar to
HBV
2-9 wk 2-4 wk
Period of
infectivity
2-3 wk in
late
incubation
and early
clinical
phase
During
HBsAg
positivity
(occasionally
only with
anti-HBc
positivity)
During anti-
HCV
positivity
During
HDV RNA
or anti HDV
positivity
Similar to
HCV
Unknown
Massive
hepatic
necrosis
Rare Uncommon Uncommon Yes Yes Unclear

222. Hepatitis
A
Hepatitis
B
Hepatitis
C
Hepatitis
D
Hepatitis
E
Hepatitis G
Carrier
state
No Yes Yes Yes No Unknown
Chronic
hepatitis
No Yes Yes Yes No Possible;
viremia per-
sistent but
hepatitis
uncertain

223. Hepatitis
A
Hepatitis
B
Hepatitis
C
Hepatitis
D
Hepatitis
E
Hepatitis
G
Prophylaxis Hygiene,
immune
serum
globulin,
vaccine
Hygiene,
hepatitis B
immune
globulin,
vaccine
Hygiene Hydiene,
HBV
vaccine
Hygiene,
sanitation
Hygiene

224. Agent Marker Definition Significance
Hepatitis A
virus (HAV)
Anti-HAV
IgM type
IgG type
Antibody to
HAV
Current or recent infection or
convalescence
Current or previous infection;
conferring immunity
Hepatitis B
virus (HBV)
HBsAg
HBeAg
HBV surface
antigen e
antigen; a
component of
the HBV core
Positive in most cases of acute
or chronic infection
Transiently positive in acute
hepatitis B
May persist in chronic infection
Reflection of presence of viral
replication, whole
Dane particles in serum, and
high infectivity

225. Agent Marker Definition Significance
Anti-HBe Antibody to e
antigen
Transiently positive in
convalescence
Possibly persistently present in
chronic cases
Usually a reflection of low
infectivity
Anti-HBc
(IgM or IgG)
Antibody to HBV
core antigen
Positive in all acute and
chronic cases
Reliable marker of infection,
past or current IgM anti-HBc a
reflection of active viral
replication
Not protective

226. Agent Marker Definition Significance
Anti-HBs Antibody to HBV
surface antigen
Positive in late
convalescence in most acute
cases
Conferring immunity
Hepatitis C
virus (HCV)
Anti-HCV Antibodies to a
group of
recombinant HCV
peptides (C22-3,
C200)
Positive on average 15 wk
after exposure; not
protective
Persistent in chronic
infection
Hepatitis D
virus (HDV)
Anti-HDV
(IgM or IgG)
Antibody to HDV
antigen
Acute or chronic infection;
not protective

227. • An acute or chronic illness involving the liver
with necrosis, inflammation & scarring
• 95% develop a fatty liver which is a reversible
process
• Encephalopathy & death 20%
• 30% go on to cirrhosis within 6 mo
• 50% of those abstaining for 6 mo recover
completely
Alcoholic Hepatitis

228. • Most patients are symptomatic. The most common
complaints are:
– Anorexia, nausea, vomiting
– Abdominal pain (RUQ)
– Fever (due to infection or inflammation of liver)
– Weight loss due to anorexia
– Jaundice is usually mild
– Diarrhea which is due to portal hypertension
Alcoholic Hepatitis Symptoms

229. • Jaundice
• Spider angiomas
• Palmar erythema
• Clubbing of fingers
• Gynecomastia
• Hepatomegaly
Alcoholic Hepatitis Physical Findings

230. • Splenomegaly
• Pruritis
• Ascites
• Edema
• Caput medusa
• Testicle atrophy
• Dark urine, light stool

233. • Hepatic insufficiency: which is responsible
for the following:
– Coma
– Jaundice
– Ascites
– Anemia
– Hemorrhagic tendency
– Ankle edema
Alcoholic Hepatitis Damage to liver causes

234. • Hyperestrinism: which is responsible for:
– Spider nevi
– Alopecia
– Gynecomastia
– Palmar erythema
– Testicle atrophy
Alcoholic Hepatitis Damage to liver causes

235. • Portal Hypertension: causes the
following:
– Esophageal varices
– Splenomegaly
– Caput medusa
– Ascites
Alcoholic Hepatitis Damage to the Portal System

236. • Hypersplenism: causes the following:
– Anemia
– Leukopenia
– Thrombocytopenia
Alcoholic Hepatitis Damage to the Portal System

238. • A. Laboratory Test:
– The SGOT (AST) 2-10x’s normal
– SGPT (ALT) is less elevated
– Bilirubin mild to moderate
– Alk phos is usually 2-3x’s normal
Alcoholic Hepatitis Diagnostic Studies

239. – Globulins elevated with reverse A/G ratio
– Prothrombin time elevated (poor prognosis)
– Leukocytosis
– Blood NH3 (Ammonia) level

240. • B. Ultrasound
• C. Liver Biopsy
– To be done early, but not to be done if PT/PTT are
elevated
– Microscopic exam confirms the diagnosis
Alcoholic Hepatitis Diagnostic Studies

241. – Findings of biopsy
• Hepatocellular necrosis
• Inflammatory exudates
• Fibrosis
• Fatty infiltration
• Cholestasis
• Hemosiderosis (iron accumulation in the lungs)

245. • 1. Mortality of 10-15%
• 2. Worsening of symptoms in early recovery
program
• 3. Complication:
Varices gastritis
Peptic ulcer coagulopathy
Kidney infection lung infection
Peritonitis
Acute Hepatitis Course

246. • 4. Seizures with withdrawal
– Use of benzodiazepines are helpful
– Can also cause encephalopathy

247. • 5. Hepato-renal syndrome
– Development of Acute Renal Failure
– Renal functions are excluded
– There is an intense intra-renal vasoconstriction and
distribution of blood flow, causing oliguria

248. • A. Supportive therapy with bed rest
– Stop the BOOZE
• B. Diet
– Multiple vitamins: folic acid & thiamine
• Magnesium, calcium, phosphate, & glucose are carefully
monitored
– 2500 calories at least.
• Low protein if encephalopathy is present.
• Vegetable protein & milk are acceptable.
Acute hepatitis Therapy

250. • C. Benzodiazepines if
– Alcohol withdrawal
• Seizures- delerium tremons
• Encephalopathy may occur
• D. Steroids:
– Used with encephalopathy
– Minimal value in less severely ill patients
Acute Hepatitis Therapy (cont)

251. • Wernicke Encephalopathy
• Ophthalmoplegia
• Ataxia
• Nystagmus
Acute Hepatitis Nutritional Complications

252. • Korsakoff Syndrome
• Loss of new memory
• Disorientation to time & place
• Confabulation
**Treatment: large doses of thiamine Hcl

253. • 1. Pathology:
– hepatocellular necrosis similar to virus (cholestatic
reaction)
• 2. Diagnosis:
– usually established by history of drug use
• 3. Lab:
– similar to viral disease
Drug Related Hepatitis

254. • 4. Cholestatic reaction:
– impairment of bile secretion by hepatocytes
(BC pills)
• 5. Hepatocellular reaction:
– very similar to viral hepatitis
(acetominophen, isoniazid, methyldopa)

255. Drug Related Hepatitis
• 6. Symptoms:
– Arthralgias
– Fever
– Rash
– Eosinophilia
• Treatment:
– Removal of offending agent

256. Classification of Drug-Induced Liver Disease
Category Examples
Predictable hepatotoxins
with zonal necrosis
Acetaminophen
Carbon tetrachloride
Nonspecific hepatitis Aspirin
Oxacillin
Herbs (chaparral, germander)
Viral hepatitis-like
Reactions
Halothane
Isoniazid
Phenytoin
Cholestasis Estrogens
Noninflammatory 17 α-Substituted steroids
Chlorpromazine
Antithyroid agents

257. Category Examples
Fatty liver
Large droplet Ethanol
Corticosteroids
Small droplet Amiodarone
Allopurinol
Chronic hepatitis Methyldopa
Nitrofurantion
Tumors Estrogens
Vinyl chloride
Vascular lesions 6-Thioguanine
Anabolic steroids
Herbs (senna, comfrey)
Methotrexate
Fibrosis Methotrexate
Granulomas Allopurinol
Sulfonamides

258. Chronic
Hepatitis

259. • Refers to inflammation, necrosis & fibrosis for
at least 6 months.
• Varying from benign process to death.
• Groups:
– Viral
– Autoimmune
Chronic Hepatitis

260. – Alcoholic
– Primary biliary cirrhosis
– Drug induced liver disease
– Wilson’s disease
– Anti-trypsin deficiency
– Hemochromatosis
– Sclerosing cholangitis

261. • Viral
• Hepatitis B
• Hepatitis B with superimposed hepatitis D
• Hepatitis C
• Drugs and Toxins
• Methyldopa
• Nitrofurantoin
Causes of Chronic Hepatitis

262. • Amiodarone
• Isoniazid
• Autoimmune
• Genetic and Metabolic Disorders
• Wilson’s disease
• α1- Antitrypsin deficiency
• Nonalcoholic steatohepatitis

263. • Forms:
–A. Chronic Active Hepatitis:
• Refers to the form of CH were the liver
test & histology are compatible with
active & progressive inflammation &
necrosis
Chronic Hepatitis

264. –B. Chronic Persistent Hepatitis:
• Refers to the mild & histological non
progressive CH where the inflammation
is confirmed only to the portal tracts. The
enzymes are normal or only moderately
elevated.

265. • Mainly a disease of young women
• Most have hypergamaglobulinemia & ANA
positive
Chronic Hepatitis Autoimmune Hepatitis

266. • Patients have multisystem disease which
include:
Arthritis kidney involvement
Colitis heart
Thyroiditis portal hypertension
Pulmonary fibrosis

267. • Diagnosis:
– Consider any young female with elevated liver
function studies without course with hepatitis for
greater than 6 months
– Positive ANA
– Elevated GG =means chronic
– Liver biopsy showing chronic inflammation
Chronic Hepatitis Autoimmune Hepatitis

268. • Treatment:
–Steroids
• Decrease in symptoms
–Prognosis: is good. About 50% live
more than 15 years from the time of
diagnosis

269. • Inherited Chronic Liver Disorders
– A. Wilson’s disease
– B. Hemachromatosis
– C. Alpha 1-antitrypsin deficiency
– D. Reye syndrome
Other causes of Chronic Hepatitis

270. • Pathogenesis:
– a rare treatable genetic disorder of copper
metabolism.
– There is an abnormal accumulation of copper in the
hepatocytes.
– This is a metabolic disorder affecting basal ganglia,
eyes, & kidney.
Wilson’s Disease

271. – The defect is in the ceruloplasm which
carries the copper.
– The serum ceruloplasm & copper are both
low (copper low b/c it can’t be carried)

272. • Diagnosis:
– Made by seeing neurological, psychiatric,
hepatitis, cirrhosis in a young person.
– Liver disease with the Kayser-Fleischer ring
in the eyes in the young is characteristic
Wilson’s disease (cont)

275. Kayser – Fleischer Ring

276. • Pathogenisis: A group of disorders with
excessive absorption of iron.
• The iron is layed down in liver, heart,
pancrease, kidney, & skin (bronze
diabetes)
– Primary cause unknown
Haemochromatosis

277. – Secondary- Iron overload :
• anemias
• cirrhosis
• Dietary
– Diagnosis:
• Lethargy, weakness in men 40-60 yo
• Skin hyperpigmentation
• Diabetes 30-60% of pt’s
• arthopathy

279. • In children associated liver disease
• In teenagers & adults, a progressive liver
disease with pulmonary manifestations
• Pathogenesis: Alpha 1-trypsin is a potent
protease inhibitor found in the serum, body
fluids, & tissues
Alpha 1-Antitrypsin Deficiency

280. • It is synthesized by the liver to protect from
tissue injury resulting from protease like
trypsin

282. • An illness seen in the pediatric age group
associated with the flu
• Symptoms: Nausea, vomiting, hyperactivity,
confusion, seizures, & coma, Increasing
drowsiness, Belly Pains
Reye’s Syndrome

283. • On liver biopsy there are fatty infiltration
• Chemistry: elevated liver enzymes, NH3
***NEVER give Aspirin to children with
varicella infection (chicken pox), or during
flu sx.***

284. • only happens in kids less than 15 years old.
• The cause is unknown, but it is strongly
associated with Aspirin use during flu's.
• The liver becomes inflamed and destroyed
for unknown reasons.
REYE'S SYNDROME

285. • It is important because Reye's syndrome kills
about half of kids who get it.
• NEVER give aspirin containing medications
to your kids under 15 years old for fever
control.
• Use Acetaminophen/ Ibuprofen instead.

288. • May result from:
– A. Slow deterioration as part of a chronic
progress
– B. Rapid worsening after repeated injuries
– C. catastrophic event such as massive
necrosis
Hepatic (Liver) Failure

289. • Causes:
– 1. Functional liver failure without overt
necrosis
• Reye’s syndrome, tetracycline toxicity
– 2. Chronic liver disease
• Chronic active hepatitis
• Cirrhosis

290. – 3. Fulminate failure: refers to acute severe
impairment of liver function with
encephalopathy & coma in patients who
have had liver disease for less than 8 weeks

291. Management of Selected Problems
in Fulminant Hepatic Failure
Complications Pathogenesis Management
Hepatic
encephalopathy
Liver failure Search for treatable causes, i.e.,
hypoglycemia, drugs used for
sedation, sepsis, gastrointestinal
bleeding, electrolyte imbalance,
decreased PO2,
increased PCO2
;
lactulose
Cerebral edema Unknown Elevate head of bed 20-30
degrees; hyperventilate (PCO2
25-30 mm Hg); mannitol, 0.5-1
g/kg IV bolus over 5 min;
pentobarbital infusion; urgent
liver transplantation

292. Complications Pathogenesis Management
Coagulopathy and
gastrointestinal
hemorrhage
Decreased synthesis
of clotting factors
Gastric erosions
Vitamin K; fresh-frozen plasma if
actively bleeding and for
prevention of bleeding; IV H2-
antagonist prophylaxis
Hypoglycemia ↓ Gluconeogenesis
Insulin degradation
IV 10% dextrose, monitor every 2
hours; 30%-50% dextrose may be
needed
Agitation May be due to:
Encephalopathy ↑
Intracranial pressure
Hypoxemia
Search for treatable causes (i.e., ↓
PO2, skin ulcersl lacerations, or
abscesses); soft restrains; if
severely agitated and a concern of
injury, consider sedation along
with mechanical ventilation to
protect airway

293. • Clinical features:
– Jaundice
– Hypoalbuminemia
– Hyperestrogenism which causes
• Testicular atrophy
• Gynecomastia
• Palmar erythema
• Spider angiomas
Hepatic Failure (cont)

294. – Hepatorenal Syndrome
– Fetor odor
– Coagulopathy

295. • CLAPS:
Clubbing
Leukonychia
Asterixis
Palmar erythema
Scratch marks
Liver failure (chronic): signs of found on the
arms Mneumonic

296. Complications of hepatic failure

297. • Hepatic encephalopathy:
– A metabolic disorder of the CNS system &
neuromuscular system with slight changes
in the brain (edema)
Hepatic Failure (cont)

298. – Clinical Features:
• Confusion
• Flapping tremor (asterixis)
• Drowsiness
• Coma death
Caused by elevated levels of NH3 (ammonia)

299. • HEPATICS:
Hemorrhage in GIT/ Hyperkalemia
Excess protein in diet
Paracentesis
Acidosis/ Anemia
Trauma
Infection
Colon surgery
Sedatives
Hepatic encephalopathy: precipitating
factors Mneumonic

301. • Treatment:
– Remove precipitating causes (drugs/ETOH)
– Decrease enteric toxins (BUN-NH3)
– Gut enema
– Low protein diet
– Neomycin 1-2 gms Q 2 hrs PO
Hepatic failure (cont). Hepatic Encephalopathy

302. –Lactulose 50 ml orally Q 2hrs until
diarrhea ensues. Then reduce dosage
until there are two stools per day
– Transplantation:
• Any young patient with progressive disease
• Metabolic disease: wilson’s, alpha
antitrypsin def.

303. • Etiology: triad
– 1. necrosis
– 2. regenerating nodules
– 3. fibrosis
• Categories:
– Major
• Alcoholic (#1 cause in western world)
• Post necrotic
Cirrhosis

304. –Minor
• Wilson’s disease
• Haemochromatosis
• Biliary
• Chronic hepatic congestion

305. –Budd-Chiari syndrome
»uncommon condition induced by
thrombotic or nonthrombotic
obstruction to hepatic venous
outflow
–Cardiac
»Right sided heart failure
»Tricuspid insufficiency

306. • HEPATIC:
Hemochromatosis (primary)
Enzyme deficiency (alpha-1-anti-trypsin)
Post hepatic (infection + drug induced)
Alcoholic
Tyrosinosis
Indian childhood (galactosemia)
Cardiac/ Cholestatic (biliary)/ Cancer/ Copper
(Wilson's)
Causes of hepatic cirrhosis Mneumonic

307. • Common causes are ABC:
Alcohol
B (Hepatitis)
C (Hepatitis)
Cirrhosis: differential:
common and rarer
Mnoumonic

308. • · Rarer are also ABC:
Autoimmune
Biliary cirrhosis
Copper (Wilson's)

309. Cirrhosis

310. Cirrhosis resulting from chronic viral hepatitis

311. Budd-Chiari syndrome. Therombosis of the major hepatic
veins has caused extreme blood retention in the liver.

312. • Biliary Cirrhosis:
– One of the more common causes of nonalcoholic liver
disease
– Pathology is destruction of the intrahepatic bile ducts
– 90% are found in middle age females
– Most common symptoms are fatigue & pruritis
– Antimitochondrial antibodies (90%)
• Order after all hepatitis profile excluded
Cirrhosis (cont)

313. • Complications of cirrhosis:
– Spontaneous bacterial peritonitis (SBP)
which occurs in 10% of alcoholic cirrhosis
(E. coli)
Cirrhosis (cont)

314. –Ascites:
• Refers to the accumulation of excessive
volumes of fluid within the peritoneal
cavity
• Always a poor prognostic sign
• Ultrasound & CT scans are best method
of detection of small amounts of fluid.
Flat plate has ground glass look.

315. • Ascites (cont)
– Diagnosis of ascites:
• Bulging flanks
• Umbilical hernia
• Shifting dullness
• Scrotal edema
• Right sided pleural effusion
Cirrhosis (cont)

316. –Paracentesis:
• 50cc of fluid removed, look at color
• CBC, WBC, protein, LDH, glucose,
amylase, albumin
• Gram stain, AFB, fungus cultures,
cytology

317. Clinical and Laboratory Features of Cirrhosis
Clinical Laboratory
Hepatocellular Dysfunction
Jaundice Hyperbilirubinemia
Spider angiomas Edema
Palmar erythema Low serum blood urea nitrogen
Gynecomastia Prolonged prothrombin time
Loss of body hair Hyperammonemia
Testicular atrophy Thrombocytopenia
Dupuytren’s contracture Leucopenia
Muscle wasting ─

318. Clinical and Laboratory Features of Cirrhosis
Clinical Laboratory
Hypoalbuminemia Low serum albumin
Bruising ─
Signs of hepatic encepha-lopathy ─
Fetor Hypertension
Splenomegaly ─
Ascites ─
Caput medusae ─
Variceal bleeding ─

321. • Pathophysiology:
– Alteration of hepatic blood flow causing
portal hypertension.
– Reduction in liver function:
• Reduction in synthesis of albumin & coagulation
proteins
• Reduction in detoxification of bilirubin,
ammonia, & drugs
Ascites (cont)

322. Ascites

323. • Complications of ascites:
Dyspnea vomiting
Decreased cardiac output hydrothorax
Anorexia scrotal edema
Reflux esophagitis
Ascites (cont)

324. • Treatment:
– Improve hepatic function
– Restrict sodium & fluid intake
– Aldactone which inhibits aldosterone
– Paracentesis (removal of fluid with addition
of IV albumin)

325. –Shunts
–Abstain from alcohol
–Diuretics
• Aldactone
• Lasix

326. • Treatment (cont):
– Supportive
• Nutrition high calories, low protein with
encephalopathy
• Minerals & vitamins
• Sodium restriction
• Copper restriction if wilson’s disease
Ascites treatment (cont)

327. – Neomycin & Lactulose if NH3 elevated
– Liver Transplants

328. • Classification:
– Portal vein (prehepatic)
– Intrahepatic (sinusoids)
– Hepatic (posthepatic) (Budd Chiari- usually
due to tumor)
Portal Hypertension

329. • Findings:
– Ascites
– Varices
• Gastric, esophageal, hemorrhoids
• Caput medusa
– Encephalopathy
– Splenomegaly which causes:
• Sequestration & destruction of RBC’s
• Neutropenia
• thrombocytopenia

330. Presinusoidal
Portal or splenic vein occlusion
(thrombosis, tumor)
Schistosomiasis
Congenital hepatic fibrosis
Causes of Portal Hypertension

331. Sarcoidosis
Sinusoidal
Cirrhosis (all causes)
Alcoholic hepatitis
Postsinusoidal
Veno-occlusive disease
Budd-Chiari syndrome
Constrictive pericarditis

332. Increased portal blood flow
Splenomegaly not due to liver disease
Arterioportal fistula

333. • Diagnosis:
– Barium swallow for varices of esophagus
– Angiography
– Endoscopy
Portal Hypertension (cont)

334. • Treatment:
– Transfusion of platelets
– Vasopressin decrease splanchnic blood flow
– Balloon tamponade
– Endoscopic sclerotherapy
– Portal shunts

339. Manifestations of Portal
Cirrhosis
Primary Alteration in Function Manifestation
Hepatocellular Dysfunction
Impaired metabolism of sex
hormones
Female: menstrual disorders
Male: testicular atrophy,
gynecomastia, decrease in
secondary sex characteristicsSkin
disorders: vascular spiders and
palmar erythema
Impaired synthesis of plasma
proteins
Decreased levels of serum albumin
with development of edema and
ascites Decreased synthesis of
carrier proteins for hormones and
drugs

340. Decreased synthesis of blood-
clotting factors
Bleeding tendencies
Failure to remove and
conjugate bilirubin from
the blood
Jaundice
Impaired bile synthesis Malabsorption of fats and fat-
soluble vitamins
Impaired metabolism of drugs
cleared by the liver
Risk of drug reactions and
toxicities
Impaired gluconeogenesis Abnormal glucose tolerance
Decreased ability to convert
ammonia to urea
Elevated blood ammonia levels,
encephalopathy

341. • Signs of liver disease & causes
– Jaundice- diminished bilirubin secretion
– Fetor hepaticus- sulfur compounds produced
by intestinal bacteria, not cleared by liver
Liver Review

342. – Spider angiomas, palmar erythema, &
gynecomastia- elevated estrogen levels
– Ecchymoses- decreased synthesis of clotting
factors
– Xanthomas- elevated cholesterol levels

343. • Hypoglycemia- decreased glycogen stores
• Hypersplenism- portal hypertension
• Encephalopathy, asterixis- portosystemic
shunt, NH3
Liver Review

344. • Hepatorenal syndrome (rapid decline of GFR)-
renal failure of unknown pathogenesis,
kidneys are normal (may be transplanted),
assoc c ascites, almost always fatal

345. • Liver cell damage= AST, ALT
• Bile duct obstruction= alk phos
• Cholestasis= bilirubin
• Hep A: IgG antibodies= previous exposure
IgM antibodies= recent infection
Liver review

346. • Hep B: HBsAg-acute or chronic inf. (used for
blood bank
screening
HBeAg- high degree of infectivity
Anti-HBc- earliest indicator of acute
infection
Anti-HBe- resolution of acute infection
Anti-HBs- indicates immunity (post
infection or vaccine)

347. • The liver is the largest internal organ
• The liver has a right lobe and a left lobe.
• The liver holds about 13 percent of the body's blood
supply at any given moment.
• The liver is visible on plain abdominal film
• Ultrasound exam of the liver shows size and
consistency
• The liver has the ability to regenerate
Liver Jeopardy Facts