Lesson 2

Liver and Gallbladder disorders

 Liver structure
• The liver is made of cells called
hepatocytes.

Functions:
• formation and excretion of bile
• nutrient metabolism
• urea formation
• storage of glucose (as glycogen),
proteins, vitamins and minerals
• detoxification of drugs
• Creation of Bilirubin from red
blood cell breakdown
 Liver
• Because the liver is central to metabolic
disposition of virtually all drugs and foreign
substances, drug-induced liver toxicity is a
potential complication of many medications
• As the major drug-metabolizing and
detoxifying organ in the body, the liver is
subject to potential damage from the
enormous array of pharmaceutical and
environmental chemicals
 Drugs & liver
• Numerous host factors contribute to the
susceptibility to drug-induced liver disease
including:
– Genetic predisposition, age, underlying chronic
liver disease, diet and alcohol consumption,
multiple interacting drugs
• Women generally predominate among
persons with drug-induced liver disease
• Drugs and chemicals can exert their effect by
causing hepatocyte injury and death or by
cholestatic liver damage due to injury of
biliary drainage structures
Liver and gallbladder relationship
 Liver blood vessels
• 80% of the liver blood is supplied by the portal
vein which contains the blue (oxygen poor)
blood
• Portal vein carries this blood from the GI tract.
• The rest of the liver blood supply (20%) is by
the hepatic artery which contains red (oxygen
rich) blood.
 What is bile?
• It is a dark fluid made in
the liver and stored in
the gallbladder
• It is important as it
emulsifies fat (breaks it
down) for absorption in
the stomach
 Bile Ducts
• After bile is formed in the
hepatocytes, it enters the
left & right hepatic ducts.
• These two ducts connect
and form common hepatic
duct
• The cystic duct which
comes from the gallbladder
connected to the common
hepatic duct and forms the
common bile duct.
 Cholestasis
• Cholestasis represents a decrease in bile flow

• May be cause by intrinsic liver disease, in

which case it is referred to as intrahepatic
cholestasis, or by obstruction of the large bile
ducts, a condition known as extrahepatic
cholestasis
 Pruritis
• Pruritus (itchiness) is the most common
presenting symptoms in persons with
cholestasis, probably related to an elevation in
plasma bile acids
 The Bilirubin Story
• This is a yellow compound that is released
when an old or damaged or diseased red
blood cell is broken down
 Bilirubin
• Recall a red blood cells
contains hemoglobin:
When a red blood cell is
broken down,
hemoglobin splits up into
heme (iron) and a globin
(protein)
 Bilirubin
• The heme (iron) goes to
the bone marrow to
make new red blood
cells
• The globin (protein) is
broken down in the liver
and creates bilirubin as
a waste product
 What happens next?
• Bilirubin is released in bile, urine and feces
and is responsible for a yellow/brownish
colorization
 Cirrhosis
• Cirrhosis is when the hepatocytes undergo
necrosis (death) and are replaced by useless
fibrous scar tissue in the liver
 Causes of Cirrhosis
• alcohol
• Infection: chronic viral
hepatitis
• chronic drug abuse
 Symptoms of cirrhosis
• skin color changes due to increasing bilirubin –
jaundice
• RUQ pain due to scar tissue in the liver
• CNS manifestations like tremor (shaking),
behavior changes, delirium
 Alcoholic Liver Disease
• It’s a disease state of
liver attributable directly
to the effect to alcohol
abuse.
• There are 3 stages of
liver disease from
alcoholism:
1. Fatty liver
2. Alcoholic hepatitis
3. Alcoholic cirrhosis
 Fatty Liver
• Fatty liver is the lipid accumulation in the
hepatocytes.
• Reason is alteration of fat metabolism in the liver
which caused by alcohol
• In these patients, the liver is massively enlarged
(hepatomegaly)
• Most causes are reversible by stopping drinking
alcohol, but some of them can convert to
cirrhosis.
 Alcoholic Hepatitis
• Alcoholic hepatitis is inflammation of liver
due to alcohol irritation.
• It is almost always reversible but still can
convert to cirrhosis.
 Alcoholic Cirrhosis
• Alcoholic cirrhosis is necrosis and fibrosis of
liver cells due to alcohol abuse.
• It’s never reversible and is fatal
 Alcoholic Liver Disease
• The metabolism of alcohol leads to chemical
attack on certain membranes of the liver, but
whether the damage is caused by
acetaldehyde or other metabolites is unknown
• Even after alcohol intake has stopped and all
alcohol has been metabolized, the process
that damage liver cells may continue for many
weeks and months
 Portal Hypertension
• Portal hypertension is
high blood pressure in
the portal vein
• This is due to returning
of blood back to the GI
tract because of a
blockage of the portal
vein
Factors causing portal hypertension
– cirrhosis
– inflammation of liver
(hepatitis)
– Right-sided heart
failure
 Symptoms of portal hypertension
1) Splenomegaly (spleen
enlargement)
2) Esophageal varicose
veins
3) Big umbilical veins
(spider angioma)
5) Ascites (fluid build up in
abdomen)
6) Leg edema (swelling)
 Treatment of cirrhosis
• Replacement of
nutrients and vitamins

• The typical treatment is

replacement of the liver
 Hepatitis
• Hepatitis is inflammation of liver. The
inflammation of liver can cause by virus,
bacteria, parasites, drugs, alcohol.
• The most common type is viral hepatitis
5 types of viral hepatitis
• HAV: hepatitis A virus
• HBV: hepatitis B virus
• HCV: hepatitis C virus
• HDV: hepatitis D virus
• HEV : hepatitis E virus
 Hepatitis A and E
• Nearly identical (the
only thing different is
the virus causing it)
• benign, self-limiting
• transmitted oral/fecal
• No carrier state
 Hepatitis B and D
• These are chronic
• Spread by sex, dirty
needles or across
placenta
• A carrier state exists
whereby you can pass it
on with no symptoms!!
• D does not exist without
a co-infection from B!!!!
• High mortality rate
 Hepatitis C
• Chronic, can be fatal
• Most common type
• Does have a carrier
state as well
• Most common spread is
dirty needles, but sex as
well
 Symptoms of hepatitis
Generally all types of hepatitis manifest with:
• malaise (feeling crappy)
• anorexia (lack of eating)
• jaundice
• hepatomegaly (liver enlargement)
• pain in RUQ (right upper quadrant)
• vomiting
• low grade fever
 Jaundice (Icter)
• Jaundice is yellowing of
skin or the sclera due to
buildup of the bilirubin
• it is not a disease, but a
sign of a liver disorder
• Bilirubin comes from red
blood cell breakdown,
enters the liver and
ultimately goes to the
intestines where it makes
our stool brown
 Causes of Jaundice
• Jaundice can occur because of direct disease
to the liver (intrahepatic) like cancer, cirrhosis
or hepatitis

• It may also occur for other reasons not

involving the liver (extrahepatic)
 Causes of Jaundice
• Intrahepatic or hepatocellular jaundice is
caused by disorders that affect the ability of
liver to remove bilirubin from the blood, so
that it can be eliminated in the bile
• Liver disease such as hepatitis and cirrhosis
are the most common causes of intrahepatic
jaundice
 Extrahepatic causes
• Because bilirubin comes
from the blood, certain
blood diseases like
hemolytic anemia can
cause it
• Can also be because of
gallstones causing back
up of bilirubin in the
blood
 Jaundice Symptoms
• Itchiness (acid irritation
of skin)
• Yellowing of the skin
• Very dark urine
• Very pale stools
 Causes of Jaundice
• Can also occur in a
newborn as the liver is
still developing.
• Not an issue, it will
correct itself with time
 Liver failure
• The most severe clinical consequence of liver
disease is hepatic failure

• 80%-90% of hepatic functional capacity must

be lost before liver failure occurs
• Manifestations reflect various synthesis,
storage, metabolic, elimination functions of
the liver
 Liver cancer
– Hepatocellular cancer is one of the few cancer for which
an underlying etiology can be identified in most cases;
usually occurs in a background of chronic liver disease

• Among the factors identified as etiologic agents in

liver cancer are chronic viral hepatitis (HBV, HCV,
HDV), cirrhosis, long term exposure to environmental
agents such as aflatoxin, and drinking water
contaminated with arsenic

• Manifestations often are insidious in onset and

masked by those related to cirrhosis or chronic
hepatitis
 • Metastatic
tumours of the
liver are much
more common
than primary
tumours;
common
sources include
colorectal
cancer and
spread from
breast, lung, or
urogenital
cancers
Liver cancer
 Gallbladder (Chole…)
• Two most common
gallbladder diseases:

1) Cholelithiasis
(gallstones)
2) Cholecystitis (gall
bladder inflammation)
 Cholelithiasis
• is stone formation in gallbladder
• 80% of these stones are from cholesterol and
20% are from minerals or ions (iron, calcium
and phosphorous)
 Who’s at risk?
• The predisposing
factors of getting
gallstones is defined as
four “F’s”
1. Female
2. Fat
3. Forty/Fifty
4. Fertile
 What causes an attack?
• Most common reason:
ingestion of a fatty
meal!
 Pain and Cholelithiasis
• The pain of biliary colic usually is abrupt in
onset and increases steadily in intensity until it
reaches a climax in 30-60 minutes
– The upper right quadrant, or epigastric area, is the
usual location of the pain, often with referred pain
to the back, above the waist, the right shoulder,
and the right scapula or the mid-scapula region
– Pain usually persists 2-8 hours and is followed by
soreness in the upper right quadrant
 Treatment for gallstones
• ultrasound
fragmentation (crashing
of stones)
• Complicated cases is
best treated by surgical
involvement
(cholecystectomy)
 Living without a gallbladder
• No more bile being
made, thus fat digestion
becomes more difficult
• Encourage low fat diet
• Will get more bowel
movements and
possibly steatorrhea
 Cholecystitis
• inflammation of
gallbladder typically due
to irritation by
gallstones
• Gallstones cause stasis
(blockage) of bile flow
making a good
environment for growth
of bacteria which cause
the inflammation
 Acute Cholecystis symptoms
• Pain and tenderness in
RUQ
• May radiate to right
shoulder
• Nausea
• Low grade fever
 Chronic Cholecystitis symptoms
• These patients may be
asymptomatic
• steatorrhea which is
fatty and smelly stool
• flatulence
• belching
• bloating
 Gallbladder cancer
• Slightly more common in women than men
and occurs most often in the seventh decade
of life
• Onset of symptoms is usually insidious, and
they resemble those of cholecystitis
• About 80% - 85% of people with gallbladder
cancer have cholelithiasis
 Self Test Questions
• Which hepatitis is (are) benign?
• What is the most common type of hepatitis?
• What is the most common route of spread of Hep C?
• Jaundice is due to increasing levels of what?
• What is ascites?
• What is cholecystitis?
• What is cholelithiasis?
• What are gallstones usually made of?
• Where does bilirubin come from?
 Self Test Questions
• What triggers a gallstone attack?
• Who is at risk for developing gallstones?
• Where would pain from the liver/gallbladder be located?
• What does steatorrhea mean?
• What blood vessel supplies most of the liver’s blood
supply?
• What are the 3 stages of alcoholic liver disease in order?
Which are reversible?
• What is the importance of bile?