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Diseases of the liver
Liver
Normal liver has smooth
brown surface
Weight: 1200-1600 g

Maintaining body metabolic homeostasis:
 Lipid and carbohydrate metabolism: production
and secretion of glucose
 Protein synthesis: albumin, coagulation factors
 Detoxification and drug metabolism
 Excretion of bilirubin
 Synthesis and excretion of bile salts
Liver anatomy and
histology
Patterns of hepatic injury

Inflammation

Steatosis: accumulation of fat droplets within
hepatocytes

Cell death: those cells closer to the central vein are more
susceptible to ischemia, toxins and drugs leading to
“centri-lobular” necrosis

Fibrosis: Irreversible, affect blood flow and hepatocyte
function

Cirrhosis: End stage liver disease with diffuse fibrosis
and regenerating nodules
Steatosis
Alcohol, Obesity, Diabetes
Hyperlipidemia
Clinical picture:
Silent, or fatigue,
malaise, right upper
quadrant discomfort
Liver cirrhosis

Definition: bridging fibrous septa and parenchymal
nodules with disruption of architecture.

End stage for many diseases affecting the liver
Mechanism: cell death, regeneration and fibrosis
Clinical consequences of liver disease

Hepatic dysfunction:

Decrease synthesis capacity leading to :
 Hypoalbuminemia:
edema, ascitis, muscle
wasting, weight loss
 Hypoglycemia:
 Coagulation
weakness and syncope
factor deficiency: bleeding

Decrease detoxification capacity leading to:
 Hyperammonemia
and increase toxic
metabolites: Encephalopathy (altered behavior
and consciousness that may lead to deep coma
and death)
 Injury

to other organs by active toxins
Hepato-renal syndrome:
 Renal
failure without intrinsic or functional
causes of renal failure.
Clinical picture liver disease

Jaundice: yellow discoloration of skin and sclera due to
accumulation of bilirubin

Cholestasis: systemic accumulation of bilirubin, bile salts and
cholesterol (usually secondary to obstruction)

Portal hypertension in cirrhosis: increased resistance to portal
blood flow


Esophageal varices

Ascitis

Splenomegaly

Hemorrhoids
Malignancy on top of cirrhosis
Jaundice

Accumulation of bilirubin in tissue leading to yellow
discoloration of skin and sclera

Normal serum level: 0.3-1.2 mg/dl; jaundice appears
with levels above 2.0-2.5 mg/dl

Source of bilirubin: the breakdown of old red blood cells
in the spleen releases heme that changes into bilirubin by
specific enzymes.
Bilirubin
Conjugation is a function of the liver by
adding glucuronic acid to bilirubin

-
-
Unconjugated
Albumin
bound
Insoluble in
water, toxic

-
-
Conjugated
Loosely bound
to albumin
Water soluble,
non-toxic,
excreted in
urine
Laboratory evaluation of liver disease

Hepatocyte function:




Hepatocyte injury (enzymes normally present inside the
hepatocytes and released with injury):




Serum albumin
Prothrombin time: prolonged in liver cirrhosis
Serum ammonia
Serum aspartate aminotransferase (AST)
Serum alanine aminotransferase (ALT)
Serum lactate dehydrogenase
Biliary excretory function:



Serum bilirubin
Serum alkaline phosphatase
Serum gamma-glutamyl transpeptidase
Selected disorders of the liver

Viral hepatitis

Drug-induced hepatitis

Autoimmune hepatitis

Alcoholic hepatitis

Hemochromatosis

Wilson disease

Neoplasms of the liver
Hepatitis A virus

RNA virus

Mode of transmission: contaminated water and food

Incubation period: 2-6 weeks

Virus shedding: 2-3 weeks before and 1 week after
appearance of jaundice

No carrier state

No increase risk for chronic hepatitis, or carcinoma

Because viremia is transient, no need to screen
donated blood
Hepatitis B virus

Ds-DNA virus

Mode of transmission: parenteral (blood products,
contaminated needles and IV drug abuse), and body
fluids (including saliva)

Incubation period: 4-26 weeks

Carrier state: yes
Hepatitis B infection: Possible outcomes

Possible outcomes of infection:
Subclinical or acute hepatitis with recovery and
clearance (85%); 1% of those may develop
fulminant hepatitis and death
 Healthy carriers (10%)
 Persistent infection (5%): 80% recover and 20%
develop chronic hepatitis
 20% of chronic hepatitis patients develop cirrhosis
and 10% of those develop hepatocellular carcinoma

Hepatitis C

Ss-RNA virus

Mode of transmission: parenteral, sexual, 40%
unknown source. It is present in the saliva.


Incubation period: 2-26 weeks
HCV is the leading cause for chronic liver disease
Outcomes of infection:
Hepatitis D

Defective RNA virus that needs Hep B capsule to
replicate

Mode of transmission: Parenteral

Coinfection of B and D: mild disease with recovery in
most cases, <5% chronic hepatitis

Superinfection by D after B: accelerated more severe
hepatitis; 80% chronic hepatitis
Hepatitis E

ssRNA virus

Mode of transmission: water-borne

Incubation period: 2-8 weeks

Endemic in certain populations; 40% in Indian
population

Self-limited infection but with higher mortality in
pregnant females
The points to remember
Hepatitis A
Hepatitis B
Hepatitis C
Transmission
Oral-fecal
Parenteral
Parenteral
Carrier state
None
Present
Present
Chronic
hepatitis
None
5-10%
>70%
Fulminant
hepatitis
0.1%
0.1-1.0%
Rare
Carcinoma
No
Yes
Yes
Drug-indued hepatitis

Predictable or unpredictable (idiosyncrasy)

Mechanisms: direct toxicity, conversion of drug to an
active toxin, immune-mediated

A long list of drugs can cause different forms of injury:
hepatitis, fibrosis, granulomas, necrosis, cholestasis,
vascular disorders and neoplasia

Example: Acetaminophen overdose induces centrilobular
necrosis
Autoimmune hepatitis

More in females (70%)

The absence of serologic markers for viral hepatitis

Elevated serum IgG levels

High titers of autoantibodies (antinuclear, anti-smooth
muscle, and anti-microsomal)

Associated with other forms of autoimmune disorders
such as rheumatoid arthritis and ulcerative colitis

Risk for cirrhosis is 5%

Respond to immunosuppressive drugs
Alcoholic liver disease

100,000 death annually related to alcohol; 20,000 are
related directly to end-stage liver cirrhosis

Effects on liver:

80% fatty liver (steatosis)

10% alcoholic hepatitis

10% cirrhosis
Hereditary hemochromatosis

Autosomal recessive disease characterized by increased
body iron, most of which is deposited in the liver and
pancreas.

Mostly due to increased iron absorption and
accumulation over the years.

Due to mutations in the hemochromatosis gene (HFE); a
gene that regulates iron absorption.

Excess iron damages DNA, lipids and stimulates
collagen formation (fibrosis)

Clinical picture:

Males are more affected; 50-60 years old

Liver cirrhosis, skin pigmentation, diabetes
(pancreatic fibrosis), risk for hepatocellular
carcinoma.

Diagnosis: elevated serum and tissue iron.

Early detection and therapy by phlebotomy and iron
chelators lead to normal life expectancy
Wilson disease

Autosomal recessive disorder characterized by accumulation of
copper in liver, brain and eyes, among other organs

Less common than hemochromatosis

The mutated gene is located on chromosome 13; the mutation leads
to failure to excrete copper into bile, and its accumulation in tissue

Clinical picture: neuropsychiatric manifestations, acute and
chronic liver disease

Diagnosis: Clinical picture, increased hepatic and urinary copper,
and decreased serum copper binding protein.
Biliary disease

Secondary biliary cirrhosis: secondary to extrahepatic
bile obstruction by stones, atresia or tumors

Primary biliary cirrhosis: immune-mediated destruction
of intrahepatic bile ducts, more in females

Primary sclerosing cholangitis: chronic fibrosis of intraand extra-hepatic bile ducts; more in men, association
with ulcerative colitis
Tumor of the liver

Liver cell adenoma

Occurs in women of childbearing age in relation to
oral contraceptives; it regresses on discontinuation
of hormones
Well circumscribed mass
Sheets of hepatocytes with no
portal tracts
Liver cell adenoma

Significance of this benign tumor:

It may be mistaken for carcinoma

Subcapsular adenomas are at risk for rupture,
especially during pregnancy leading to lifethreatening intraabdominal hemorrhage
Hepatocellular carcinoma (HCC)

Risk factors:

Strongly associated with hepatitis B and C infection.
The carrier state for hepatitis B carries 200-fold
increased risk for HCC

Chronic liver disease (e.g. alcohol)

Hepatotoxins

Clinical picture:
Often patient already
has liver cirrhosis,
with rapid increase in
liver size, worsening
ascites, fever and pain;
elevated serum alpha
fetoprotein levels
Median survival is 7 months (death from bleeding, liver failure, or
profound cachexia)

Metastatic carcinoma

The most common malignant tumors in the liver

Usually multiple lesions

The most common primary sites are colon, lung,
breast, pancreas and stomach
The Pancreas
The Pancreas
85% exocrine: enzymes
15% endocrine: insulin,
for digestion

glucagon and others
Acute and chronic

Diabetes
pancreatitis

Tumors

Cystic fibrosis

Tumors
Pancreatic exocrine enzymes
Acute pancreatitis
Acute pancreatitis

Clinical presentation: abdominal pain radiating to the
back, elevated serum amylase and lipase, hypocalcemia

Rise in serum lipase is more specific for pancreatitis.

Complications: infections, abscess, pseudocyst

Mortality is high: 20-40%, from shock, sepsis or acute
respiratory failure, acute renal failure, disseminated
intravascular coagulation
Chronic pancreatitis

Progressive destruction of pancreatic parenchyma and
its replacement by fibrosis

Predisposing factors: alcohol, hypercalcemia or
idiopathic

30% of idiopathic cases have been found to have
mutation in CFTR gene

Complications: Pseudocyst, malabsorption, 2ry diabetes

Diagnosis: abdominal pain, malabsorption, calcifications
on X-ray
Pancreatic adenocarcinoma

The 5th most frequent cause of death from cancer

Risk factors: smoking

CP: symptoms are late; pain and jaundice

Prognosis is poor: 5% survive for 5 years
Islet cell tumors

Rare compared to adenocarcinoma

Insulinomas: secrete insulin  hypoglycemia 
behavioral changes, confusion and coma. Over
90% are benign

Gastrinomas: secrete gastrin  increase acid
production  duodenal and gastric ulcers
Gallbladder

Gallstones





Afflict 10% of adult population in
Western countries
Costs of management: $6 billion a
year
20 million patients are estimated
to have gallstones totalling several
tons
Made of cholesterol, bilirubin and
calcium salts with different
concentrations
Two types: cholesterol and
pigmented stones
Gallstones

Cholesterol
Western > others
 Advancing age
 Female sex
 Obesity
 Hyperlipidemia and
bile stasis


Pigmented
Asian > Western
 Hemolytic anemia
 Biliary infection

Complications: empyema, perforation, fistula,
inflammation, obstruction, pancreatitis
Acute cholecystitis

Calculous: acute inflammation of a gallbladder that has
stones. It may represent a medical emergency; no
associated infection initially

Acalculous: no stones, in severely ill patients, severe
trauma, burns and sepsis
Chronic cholecystitis

Almost always associated with gallstones