PREDISPOSING FACTOR PRECIPITATING FACTOR

Age (Middle Age) Lifestyle: High- Cholesterol

Intake
40 years old
Obesity

Increase activation of HMG- CoA reductase

Increase uptake of cholesterol from blood

Abnormal regulation of hepatic mechanisms for

delivering cholesterol to bile

Impaired hepatic conversion of cholesterol to bile

acid

Hepatocellular hypersecretion of cholesterol

Hepatocellular hypersecretion of cholesterol

Supersaturation of bile with

cholesterol

Abundant free- cholesterol

penetrates the gallbladder
wall and exceeds the ability
of the mucosa to detoxify it

Increase Gallbladder Gallbladder Hypomotility

volume and decrease
fractional emptying Muscular stasis appears

Intrinsic Diminished
neuromuscular muscular
dysmotility responsiveness to
cholecystokinin
 Altered relative
composition of trace
protein in bile

Balance of antinucleating
and pronucleating protein
shifts

Excess pronucleating factors

(mucin) and/ or deficiency
of antinucleating
(apolipoprotein I & II)
factors

Acceleration and nucleation

of cholesterol monohydrate
crystals in bile

Crystal nucleation and

crystal growth occur within Biliary sludge formation
the mucin gel layer

“Microstone” Formation

Vesicle fusion leads to liquid

crystals

Liquid crystals nucleate into

solid cholesterol
monohydrate crystal

Direct nucleation of
cholesterol molecules

Continued growth of the

crystals

“Macrostone” Formation
 Cholestatic Increase cholesterol
Opportunities for Stasis of bile in the
jaundice supersaturation
cholesterol gallbladder
crystallization Biliary
Bile Irritation of the Gallbladder
Cirrhosis
Gallstone formation accumulates in Progression of the mucosa
and growth liver supersaturation
Diarrhea Stimulate mucous secretion
Abnormal fat
Change in the
digestion
chemical
Interfere normal gallbladder
Gall bladder and composition of the
Bacterial emptying
duct infection bile
proliferation
Cholesterol precipitation
Contribute to stone
Cholecystitis
formation
Stone formation

Cholelithiasis Right subcostal region tenderness

Laboratory results:
Stones may become lodge in  WBC count;  AST, ALT
Nausea and the cystic or common duct  gamma- glutamyl transpeptidase
vomiting  total serum bilirubin
 direct bilirubin & alkaline
Acute cholecystitis
Fever phosphatise; prolonged PT

Stone erodes Obstruction

Tea- colored urine
Eructation, gallbladder mucosa
dypepsia Impede venous
Clay colored stool
return
Biliary colic Tissue is exposed to
concentrated bile
(RUQ pain)
Mucousal swelling Ischemia

leukocytosis

Inflammation and
distention of the
gallbladder

Ischemia of the gallbladder

wall

Necrosis and gangrene

Decreased motility and

deficient absorption
 Flatulence ,
Indigestion after Chronic cholecystitis Dyspepsia
eating fatty foods

Right upper quadrant Nausea after eating

abdominal discomfort

Heartburn

TREATMENT

MEDICAL
NPO; NGT
Low- fat diet
Analgesics
Antibiotics
Nitroglycerin
Anticholinergics
Vitamin A,D,E,K
Intravenous fluids
Administration of bile salts
Bile- binding resin such as cholestyramine
Cholesterol- dissolving agents such as Ursodiol

SURGICAL
Extracorpeal shock wave lithotripsy
Laparascopic / open cholecystectomy
Oral dissolution therapy

IF TREATED: Good prognosis IF NOT TREATED: Poor Prognosis

Gangrenous cholecystitis
Gallbladder drains and the inflammation Subphrenic abscess
process subsides after a relatively short time Pancreatitis
Cholangitis
Biliary cirrhosis
Fistulas
Rupture of gallbladder
Carcinoma
Peritonitis
Choledocholithiasis
DEATH
Narrative:

Cholesterol is rendered soluble in bile aggregation with water- soluble bile salts and
water- insoluble lecithins, both of which acts as detergents. When cholesterol concentrations
exceed the solubilising capacity of bile (supersaturation), cholesterol can no longer remain
dispersed and nucleates into solid cholesterol monohydrate crystals. Cholesterol formation
involves four (4) simultaneous defects: (1) Bile must be supersaturated with cholesterol; (2)
Gallbladder hypomotility promotes nucleation; (3) Cholesterol nucleation in bile is accelerated;
(4) Mucus hypersecretion in the gallbladder traps the crystals, permiting their aggregation in
stones.

Increased activity of HMG-CoA reductase, the rate limiting enzyme of hepatic

cholesterol synthesis may occur in association with obesity and high- caloric and cholesterol-
rich diets. With this, there will be increased hepatic uptake of cholesterol form blood leading now
to abnormal regulation of hepatic mechanisms for delivering cholesterol to bile. In some
patients, impaired hepatic conversion of cholesterol to bile acids may also occur, causing
hepatocellular hypersecretion of cholesterol resulting in an increase lithogenic cholesterol/ bile
acid ratio. Because of this mechanism, supersaturation of bile with cholesterol happens.

The abundant free cholesterol is toxiuc to the gallbladder, penetrating the wall and
exceeding the ability of the mucosa to detoxify it by esterification. Gallbladder ensues and
muscular statsis appears to result both from intrinsic neuromuscular dysmotility and from
diminished muscular responsiveness to cholecystokinin, the hormone secreted by the gut that
promotes gallbladder contraction. The relative composition of trace proteins in bile also may be
altered, such that balance of antinucleating and pronucleating proteins shifts in favour of
accelerated nucleation of cholesterol crystals. Moreover, acceleration and nucleation of
cholesterol monohydrate in bile may due to either an excess of pronucleating factors or a
deficiency of antinucleating factors. Mucin and other certain non- mucin glycoproteins,
principally immunoglobulins, appear to be pronucleating factors, while apolipoproteins AI and AII
and other glycoproteins appear to be antinucleating factors. Cholesterol monohydrate crystal
nucleation and crystal growth probably occur within the mucin gel layer. Vesicle fusion leads to
liquid crystals, which, in turn, nucleate into solid cholesterol monohydrate crystals. Continued
growth of the crystals occurs by direct nucleation of cholesterol molecules from supersaturated
unilamellar or multilamellar biliary vesicles.
 Continued growth of the crystals as well as increasing gallbladder volume and
decrease fractional emptying due to gallbladder hypomotility gives opportunities for cholesterol
crystallization, stasis of bile in the gallbladder and increase more the cholesterol
supersaturation. Stasis of bile in gallbladder can cause accumulation of bile in the liver. If the
blockage is not corrected, cholestatic jaundice may develop as a consequence of bile flow
obstruction. Lack of normal bile flow can also favour ascent of bacteria from intestine to the
biliary system. Inflammation in the ducts and gallbladder then follows from bacterial activity, as
wel as from irritation by the obstructing stone. Moreover, during stasis of bile there will be
abnormal fat digestion causing diarrhea and other signs and symptoms.

These 3 events happening during gallstone formation and gallbladder hypomotility can
lead to cholelithiasis or formation of stone in the gallbladder. Once the stone lodges in the cystic
or common duct, stones will erode in the gallbladder mucosa causing tissues to be exposed to
concentrate bile. Likewise, obstruction may occur resulting an interruption in the venous return
causing mucosal swelling then later can lead to ischemia. If these happens, acute cholecystitis
occur.

The signs and symptoms of acute cholecystitis vary with the severity of obstruction
and inflammation. Pain, initially similar to that of biliary colic is felt. It often is precipitated by a
fatty meal and may initiate with complains of indigestion. When the inflammation progresses to
involve the peritoneum, the pain becomes more pronounced in the right upper quadrant. The
right subcostal region is tender and the muscles that surround the area spasm. Fever and an
abnormally high white blood cell count attest to inflammation. Total serum bilirubin,
aminotransferase, and alkaline phosphatise levels usually are elevated. In addition, if a duct is
obstructed by a stone, severe pain may be triggered by a fatty meal, nausea, vomiting, fever
and leukocytosis may occur as well.

If acute cholecystitis remains untreated, inflammation and distention of the gallbladder

may occur leading to ischemia of the gallbladder wall, necrosis and gangrene follows and
gallbladder will become fibrotic and contracted causing decrease motility and deficient
absorption of cholesterol. These can lead to chronic cholecystitis. Chronic cholecystitis causes
milder symptoms between acute attacks. Symptoms are indigestion after eating fatty foods,
flatulence, nausea after eating, heartburn, dyspepsia and some discomfort in the right upper
quadrant.
 Furthermore, when the gallbladder is acutely inflamed, the client takes nothing by
moutn. Instead, a nasogastric tube is inserted. Treatment includes intravenous fluids to maintain
hydration, analgesics for pain, and antibiotics for the infection, low- fat diet, fat soluble vitamins
to compensate for their reduced absorption, bile- binding resin to relieve pruritus. Lithotripsy, a
non- surgical procedure using shcok waves generated by a machine called lithotripter, may be
tried to break up some types of gallstone. For surgical management, laparascopic
cholecystectomy is the treatment of choice in removing gallbladder stones. In some cases, an
open cholecystectomy is performed in which a penrose drain, a wide, flat rubber tube, or
vacuum drain, a plastic tube connected to a bulb or other collecting device, is inserted in the
wound to move serosanguienous fluid.

If treated, rains and the inflammation process subsides after a relatively short time and
there will be good prognosis. However, poor prognosis if it is left untreated and complications
will occur such as Gangrenous cholecystitis; Subphrenic abscess; Pancreatitis; Cholangitis;
Biliary cirrhosis; Fistulas; Rupture of gallbladder; Carcinoma; Peritonitis; Choledocholithiasis;
and, DEATH.
 SYMPTOMATOLOGY OF CHOLECYSTOLITHIASIS

Signs and Symptoms Presence Rationale

1. Nausea and vomiting Due to intolerance of eating
fatty foods.
2. Fever Due to inflammation, the body
tends to secrete inflammatory
mediators as a compensatory
mechanism.
3. Eructation, flatulence,  As the client eat fatty foods,
dyspepsia there is already inability to
tolerate fats since there is
already obstruction and
supersaturation of bile.
4. Biliary colic or right  Due to obstruction in the
upper quadrant pain cystic duct leading increase
pressure in the gallbladder
causing irritation of the nerve
endings.
5. jaundice Because of obstruction, there
is already backflow of bile and
hepatocellular hypersecretion
of cholesterol leads to liver
overload causing damage of
the liver
6. tea- colored urine Due to absence of
urobilinogen related to bile
obstruction
7. clay colored stool Due to absence of
urobilinogen related to bile
obstruction