Disorders of

gallbladder
PROFESSOR: CJ ASEGURADO, PhD
 Disorders of the gall bladder

• Disorders of the biliary tract

affects significant portion of the
world’s population.
• >95% of biliary tract
disease is due to
cholelithiasis
(gallstone)
• Bile is secreted by liver
and in between
meals, it is stored in
gallbladder
 Cholelithiasis
• Affect 10-20% of adult population in developed
countries
• Prevalence : certain populations are more prone
than others (US, Western Europe)
• Clinical features:
– 70-80% are asymptomatic
–Excruciating pain localised to the right
upper quadrant or epigastric region
• 2 main types of gall stones:
– Cholesterol stones
– Pigment stones

• In the West, about 90% are cholesterol

stones.
• Pigment gallstone is predominant in non-
Western populations – associated with
bacterial infection of biliary tree and
parasitic infestations.
 Cholelithiasis -cont
Risk factors :

• Estrogenic influence ( OCP and pregnancy) -

increase expression of hepatic lipoprotein
receptors
→stimulates HMG Co-A reductase
activity →enhance cholesterol uptake
and synthesis → excess
biliary secretion of cholesterol.
• Clofibrate (lipid-lowering agent)
increases hepatic HMG Co-A
reductase → reduce cholesterol 7-α
hydroxylase activity → decrease the
conversion of cholesterol to bile acids
• Obesity, and rapid weight loss also
increase biliary cholesterol
secretion.
 Cholelithiasis
Risk factors :
– Prevalence increase with age –
associated with metabolic syndrome and
obesity. More common in women (2x).
– Ethnic and geographic- Cholesterol
stone is more common in Native
American population, related to biliary
cholesterol hypersecretion.
– Hereditary- positive family history of
stones, inborn error of metabolism
associated with impaired bile salt

synthesis and secretion

– Acquired disorders- gallbladder stasis
and reduced gall bladder
motility ( in pregnancy, rapid weight
loss, spinal cord injury).
 Pathology
Cholesterol stones :
Pigment:stones

– Gross : pale yellow, ovoid, – Black stone (in sterile gall

bladder bile)- small size, fragile
firm, single to multiple with to touch, numerous, 50-70% are
faceted surfaces radioopaque
– Mostly radiolucent, 20% is – Brown stone (in infected
intrahepatic or extrahepatic
radio opaque due to the ducts)- single to a few, soft,
presence of calcium greasy, soaplike consistency due
carbonate content. to presence of retained fatty acids
released by bacterial
phospholipases on biliary
lecithins, radiolucent.
– Stone content : calcium salts of
unconjugated bilirubin, lesser
amounts of other calcium salts,
mucin glycoproteins and
cholesterol.
Cholesterol stone Pigment stone
• Content : Crystalline cholesterol • Bilirubin calcium salt is
monohydrate is predominant predominant
• Pigment stones

cirrhosis,
Black pigment hemolytic anemia
(hemoglobinopathy,
red cell disorders)

– Brown pigment – Asian

patients
(infection)
Summary :
• Complications :
– Inflammation
of gall
bladder

(cholecystitis)
– Empyema
– Perforation,
– Fistulas
• Complications
– Inflammation of
biliary tree
(cholangitis)
– Obstructive

cholestasis
– Pancreatitis
– Erode adjacent
bowel and
cause intestinal
obstruction
(gallstone ileus)
Summary:
Summary
 Cholecystitis
Definition:
Inflammation of the
gallbladder
• Can be divided into
– Acute cholecystitis
– Chronic cholecystitis
– Acute superimposed
on chronic
 Acute cholecystitis
• Can be divided into :
– Acute Calculous CS: 85-90% of the
cases. Most common complication
of gall stones and emergency
cholecystectomy
– Acute Acalculous CS (10-15% of
cases)
• Clinical features :
– progressive right upper quadrant or
epigastric pain
– Mild fever
– Anorexia
– Tachycardia
– Sweating
– Nausea
– Vomiting
– +-hyperbilirubinemia
– mild to moderate leukocytosis
– Mild ↑serum alkaline phosphatase
• In acute calculous CS : • Acute acalculous CS:
– previous episodes of pain – Proceeding in gradual
– May constitute acute symptoms, obscured by
underlying conditions
medical emergency precipitating the attacks
– May also present with mild – Predisposing conditions :
symptoms, resolved without
medical intervention, attacks • Major, non biliary surgery
subsides in 7-10 days • Severe trauma (eg: from motor
– Recurrence is common vehicle crashes)
• Severe burns
• Sepsis
• Dehydration
• Gall bladder stasis and
sludging
• Vascular compromise
• Bacterial contamination
– May complicate in gangrene
and perforation (more than
Calculous CS)
Pathogenesis of acute calculous cholecystitis
Compromise
mucosal blood
stones flow

Increase
intraluminal
obstruction to Distended gall pressure
bile outflow bladder

Prostaglandin
released
inflammation of gall bladder wall due to phospholipases
from the mucosa hydrolyzes biliary lecithin to lysolecithin
(toxic to the mucosa)

disrupt normal Mucosal and

protective mural
glycoprotein layer inflammation

exposed the mucosal

epithelium to the
direct detergent
action of bile salts
 Pathogenesis of Acute acalculous
cholecystitis
• Risk factors : sepsis and multisystem
organ failure, immunosuppression, major
trauma, diabetes mellitus, infections
• Impaired blood flow to cystic artery (end
artery)→ compromised blood flow →
ischaemia of gall bladder
• Inflammation and edema of gall bladder wall
compromising blood flow, accumulation of
microcrystals of cholesterol ( biliary sludge),
viscous bile, and gall bladder mucous
→cystic duct obstruction
 Pathology of acute cholecystitis
• Gross :
– Enlarged, tense, edematous, red or
violaceous colour (subserosal
haemorrhage)
– Fibrinous /fibrinopurulent exudate
covering the serosa
– +- stones obstructing the neck
or
cystic duct
– Lumen contains blood and pus
(empyema)
– Green black necrotic

• Microscopic :
– acute inflammation in the wall
– mucosal ulceration.
– May be associated with abscess
formation or gangrenous necrosis.
 Chronic cholecystitis
• May be a sequelae of repeated bouts of mild
to severe acute cholecystitis
• Associated with cholelithiasis > 90% of cases
• Pathogenesis : supersaturation of bile
predisposes to both chronic inflammation and
stone formation.
• 1/3 of cases : E.coli and enterococci can be
isolated from the bile
• Clinical features :
–recurrent attacks of epigastric or
right upper quadrant pain
– Nausea, vomiting and intolerance
to fatty foods.

• Pathology:
– Gross :
• smooth and glistening to dull serosa (subserosal
fibrosis)
• thickened wall, opaque gray-white appearance
• Uncomplicated cases, lumen contains clear, green,
mucoid bile and stones with normal mucosa
• Microscopic :
– Reactive proliferation of mucosa
– Inflammation (lymphocytes, plasma cells, and
macrophages in the mucosa and in the subserosal
fibrous tissue). May be minimal.
– Prominent outpouching of the mucosal epithelium
through the wall (Rokitansky Aschoff sinuses)
– Marked subepithelial and subserosal fibrosis
– +-Superimposed acute inflammation
– +-Extensive calcification within the wall
→porcelain gall bladder →increase risk of
cancer
• Xanthogranulomatous
cholecystitis: massively
thickened wall with
shrunken, nodular,
chronically inflamed with
foci of necrosis and
haemorrhage.
• Hydrops of the gall
bladder : atrophic,
chronically obstructed
gall bladder containing
only clear secretion
 Complications of cholecystitis
• Bacterial superinfection
with cholangitis or sepsis
• Gall bladder perforation and
local abscess formation
• Gall bladder rupture with
diffuseperitonitis
• Biliary enteric (cholecystenteric)
fistula, with drainage of bile into
adjacent organs, entry of air and
bacteria into biliary tree and
potentially gallstone-induced
intestinal obstruction (ileus)
• Porcelain gall bladder
with increased risk
of cancer
• Treatment : Cholecystectomy
Disorders of extrahepatic bile ducts

• Choledocholithi
asis and
cholangitis
• Secondary
biliary
cirrhosis
• Biliary atresia
Choledocholithiasis and cholangitis

• Choledocholithiasis = presence of stones within the

biliary tree
• In Western nation, almost all stones derived
from the gallbladder
• In Asia, higher incidence of primary ductal and
intrahepatic, pigmented stone formation
• 10% are asymptomatic
• Symptoms develop secondary to
– Biliary obstruction
– Cholangitis
– Hepatic abscess
– Chronic liver disease with secondary biliary cirrhosis
– Acute calculous cholecystitis
• Cholangitis = acute inflammation of the wall
of bile ducts due to bacterial infection
• Can result from any lesions obstructing the
bile flow :
– Choledocholithiasis
– Surgery involving the billiary tree
– Tumours
– Indwelling stents / catheter
– Acute pancreatitis
– Benign strictures
• Bacteria enter the biliary tree mostly through
the Sphincter of Oddi, and some through
hematogenous route.
• Ascending cholangitis = propensity of bacteria to
infect intrahepatic biliary ducts.
• Usual pathogens : E.coli, Klebsiella,
Enterococci, Clostridium and Bacteroides.
• In some population, parasitic cholangitis
also occur (Fasciola hepatica,
schistosomiasis, Clonorchis sinensis or
Opsthorchis viverrini, cryptosporidiosis)
• C/f bacterial cholangitis : fever, chills, abdominal
pain and jaundice, suppurative cholangitis,
sepsis.
 Secondary biliary cirrhosis
• Prolonged obstruction of the extrahepatic
biliary tree results in profound damage to the
liver
• Causes of obstruction: extrahepatic
cholelithiasis, biliary atresia, malignancies of the
biliary tree and head of the pancreas, strictures
from previous procedures
• Initial features of cholestasis are reversible
with correction of obstruction.
• Secondary inflammation from biliary obstruction
initiates periportal fibrogenesis, which leads to
scarring and nodule formation, generating
secondary biliary cirrhosis.
Pathogenesis
 Biliary atresia

• Major cause of neonatal cholestasis.

• Defined as complete obstruction of bile flow caused by
destruction or absence of all or part of the extrahepatic
bile ducts.
• Most frequent cause of death from liver disease in
early childhood
• Salient features :
– Inflammation and fibrosing stricture of the hepatic or
common bile ducts
– Inflammation of major intrahepatic bile ducts, with
progressive destruction of the intrahepatic biliary tree
– Florid features of biliary obstruction on liver biopsy
– Periportal fibrosis and cirrhosis within 3-6 months of birth
 Clinical features
• Neonatal cholestasis
• Slight female predominance
• Normal weight infants with postnatal
weight gain
• Acholic stool as disease evolves
- pale stool
• Lab Ix : not helpful
• Liver biopsy : evidence of bile ducts
obstruction
• Tx : liver transplantation
• Without surgical intervention,
death occurs within 2 years of
birth.
 Carcinoma of the gall bladder
• Uncommon
• Most common malignant tumour of
the biliary tract
• 2-6x in women
• More frequent in the populations of
Mexico and Chile (high incidence of
gallstones)
• In US, incidence is higher in
Hispanics and Native
Americans.
• Etiology : (recurrent trauma
and
chronic inflammation)
– Gallstones are present
in 60-90% of
the cases
– Parasitic disease of the
biliary tree
 Clinical features

• Insidious onset
• Similar to cholelithiasis (Abd pain, jaundice,
anorexia, nausea and vomiting)
• Sx of Acute cholecystitis
• Accidental finding during cholecystectomy for
symptomatic gall stone
• Tx :
– surgical resection (including adjacent liver)
– +- chemotherapy.
Pathology
• Gross : exhibit exophytic
or infiltrating patterns
(more common)
• Poorly defined areas of
diffuse thickening and
induration of the gall bladder
wall covering several cm or
involve the entire gall bladder
• The exophytic growth grows
into the lumen as an irregular,
cauliflower-like mass as well
as invades the underlying
wall.
• Mostly diagnosed at late
stage – invade liver or
spread to the bile ducts or to
the portal hepatic lymph
nodes.
 Cholangiocarcinomas
• Adenocarcinomas that arise from cholangiocytes lining the
intrahepatic and extrahepatic biliary ducts
• Extrahepatic cholangiocarcinomas (2/3) of the tumours
• Site : hilum (Klatskin tumour) or distal biliary tree
• 50-70 years old
• Asymptomatic until late stage
• Poor prognosis
• Risk factors : primary sclerosing cholangitis, fibropolycystic
diseases of the biliary tree, infestation by Clonorchis sinensis or
Opisthorchis viverrini – chronic cholestasis and inflammation →
promote somatic mutations in cholangiocytes
• Genetic changes : activating mutations in the KRAS and
BRAF oncogenes and loss of function mutations in the TP53
tumour suppressor gene.
 Clinical features
• Liver mass
• Non specific signs and symptoms :
weight loss, pain, anorexia, ascites
• If there is biliary obstruction: jaundice, acholic
stool, nausea and vomiting, weight loss
• Elevated alkaline phosphatase and
aminotransferases
• Spread to extrahepatic sites : regional lymph
nodes, lungs, bones, adrenal glands,
invasion along peribiliary nerves→to
abdomen
• Tx : surgical excision , majority non curative
• Mean survival time : 6-18 months
 Pathology
• Micro : adenocarcinoma accompanied by
abundant fibrous stroma – firm, gritty
consistency
 Interprofessional Collaborative Management for Patients
with Cholelithiasis and cholecystitis

1. Relief of pain
• Administer analgesic as prescribed. Morphine
or
Demerol (Meperidine HCI) may be used initially.
• Administer antispasmodic (anticholinergic) to
relax smooth muscles.
• NSAIDs like Toradol (Ketorolac) may be helpful
in pain management.

2. Diet.
• Maintain NPO with IV fluids administered during
nausea and vomiting episodes.
• Small, frequent feedings
• Avoid gas - forming foods.
3. Administer antiemetics for nausea and vomiting.
4. Administer medications for cholelithiasis.
(Gallstone Dissolution)

a.Chenix (Chenodiol/ Chenodeoxycholic acid).

It decreases cholesterol production, lowering
content of bile, and facilitates the dissolution of
gallstones.
b.Actigall (Ursodeoxycholic acid). Is a bile salt.
It suppresses hepatic synthesis and secretion of
cholesterol and inhibits Intestinal absorption of
cholesterol and facilitates dissolution of gallstone
(requires months of therapy).
c.Moctatin (Monoctanoid). It is used when
stones made of calcium are resistant to
dissolution by orally administered chenodiol.

Note: Major side effects of medications for cholelithiasis

are abdominal pain, diarrhea, nausea and vomiting.
Notify the physician if these signs and symptoms occur.
 5.Extracorporeal
shockwave lithotripsy to
disintegrate stones in the
biliary system. Oral
dissolution follows.

6. Surgical interventions.
a.Cholecystectomy.
Is removal of the gall
bladder.
b.Choledochotomy.
Is the removal of
stone from the
common bile duct.
Laparoscopic cholecystectomy

("lap chole") involves 3 to 4 small incisions. Gas

insufflation (with carbon dioxide) of the abdomen
is done to lift the abdominal wall. This facilitates
visualization of the gall bladder.

• After "lap chole", the client may have fluids as soon

as awake. Then, he may eat lightly for few days.

•During the first 24 hours postop, the client normally

experiences bloatedness and abdominal pain that
radiates to the shoulders. This is due to gas insufflation
of the abdomen during the procedure.

•The client may go back to normal activities to

daily living within 5 to 7 days.
Incisional or open
cholecystectomy

involves right
subcostal
incision (below
the diaphragm).
During post operative period:
(a) Position the client in semi -
Fowler's to promote lung

(b) NGT is in place, to drain gastric

content and prevent
abdominal distention

(c)Reinforce DBCT (Deep

Breathing, Coughing, and
Prevent respiratory complications
(atelectasis, hypostatic
pneumonia).
(d) Diet. Low - fat diet for 2 to 3
months. Then gradually
as introduce fats according to
client's tolerance.
• Since the gallbladder is removed, bile
directly flows from the liver to the
duodenum via the common bile duct.

• The bile is no longer concentrated by

the gallbladder.

• The bile (600 to 1,200 mls - 90 to 95%

is water) is dilute and may not be initially
be effective in emulsifying fats
adequately.

• Fat intolerance and bile intolerance are

common during the first few months.
If common bile duct
exploration was
done during open
cholecystectomy,
the client will have
a T - tube in place
the post-op period.
• The normal color of drainage from the T- tube
for the first 24 hours is reddish brown. This
is
due to combination of bile and blood.

• After 24 hours, it becomes greenish brown.

• The normal amount of drainage from the T-

tube during the first 24 hours postop is 300
to 500 mls; then up to 500 to 1,00 mls. per
day after 24 hours.

• The drainage bottle should be placed in bed,

below the level of the gallbladder. This allows
drainage of excess bile, not all of the bile.
The purposes of the T- tube are as
follow:

(a) To drain bile from the common

bile duct and Minimize the
amount of bile flowing into
the duodenum.

(b) To maintain patency of the

common bile duct
which may be swollen for the first
few days postop.

c) To prevent leakage of bile into

the peritoneum and
prevent bile peritonitis.