Cholecystitis

Lecture 31

Normally, the liver secretes approximately 500 ml of bile per day and the gallbladder concentrates it 5-10 times. The motility, concentration and relaxation of the gallbladder are under the influence of a peptide hormone, cholecystokinin (CCK), released from neuroendocrine cells of the duodenum and jejunum.

Cholesterol,Bile Pigments,Calcium Salts

CHOL, GALL Liver secretes 400-800 ml bile per day

Lecithin

Gall bladder Collects, Stores & Concentrates BileThe commonest location of impaction of a gallstone is Hartmann’s pouch?

Hartmann's pouch is an out-pouching of the wall of the gallbladder at the junction of the neck of the gallbladder and the cystic duct.

Common hepatic duct

Rt hepatic duct

Lt h duct

Obstruction of the Cystic duct

• Cholecystitis (Greek, -cholecyst, "gallbladder", combined with the suffix -itis, "inflammation") is

inflammation of the gallbladder, which occurs most commonly due to obstruction of the cystic duct with gallstones (cholelithiasis).

Gall bladder- Cholecyst, Biliary Vesicle, Bile Bladder

Classification of Cholecystitis

I. Acute Cholecystitis: calculous & acalculous

II. Chronic CholecystitisIII. Acute superimposed on chronic

Acute Calculous Cholecystitis (90%) • Acute Calculous cholecystitis is an acute

inflammation of the gallbladder, precipitated 90% of the time by obstruction of the neck or cystic duct (by gallstones).

It is the primary complication of gallstones and

the most common reason for emergency cholecystectomy.

Obstruction→Distension→Inflammation

(due to chemical irritation & Infection)

Hartmann's pouch is an out-pouching of the wall of the gallbladder at the junction of the neck of the gallbladder and the cystic duct.

The commonest location of impaction of a gallstone is Hartmann’s pouch.

Acalculous cholecystitis (10%)• Cholecystitis without gallstones,

called acalculous cholecystitis may occur in severely ill patients and accounts for about 10% of patients with cholecystitis.

Pathogenesis- Calculous cholecystitis

• Acute CALCULOUS cholecystitis results from chemical irritation and inflammation of the obstructed gallbladder.

• The action of mucosal phospholipases hydrolyzes

luminal lecithins (Phospholipids) to toxic

LYSOLECITHINS.

• The normally protective glycoprotein mucus layer is disrupted, exposing the mucosal epithelium to

the direct DETERGENT action of bile salts.

• Prostaglandins released within the wall of the distended gallbladder contribute to mucosal and mural inflammation.

• Gallbladder dysmotility develops; distention and increased intraluminal pressure compromise blood flow to the mucosa.

• Acute calculous cholecystitis frequently develops

in diabetic patients who have symptomatic gallstones.

DIABETICS

StoneObstructionDistension

Inflammation(chemical

irritation & infection: E Coli

& Streptoccocusfecalis)

Pathogenesis

Pathogenesis

Pathogenesis

Pathogenesis

Fever

Pathogenesis

Pathogenesis

Pathogenesis

Pathogenesis

Hepatobiliary Iminodiacetic acid

Hepatobiliary Iminodiacetic acidHIDA Scan

Pathogenesis- Acalculous cholecystitis

• Acute ACALCULOUS cholecystitis is thought to

result from ISCHEMIA.

The cystic artery is an end artery with essentially no collateral circulation.

NG tube feeding

Severely Ill Patients

***Risk factors for acute Acalculous cholecystitis include:

(1) Sepsis with hypotension and multisystem organ failure;

(2) Immunosuppression;

(3) Major trauma and burns;

(4) Diabetes mellitus; &

(5) Infections.

(Salmanellosis & Cholera), Parasitic infestation

Major nonbiliary surgery

Dehydration, gallbladder stasis and sludging, vascular compromise, and, ultimately, bacterial contamination.

Sepsis: The presence of pus-forming bacteria or their toxins in blood or tissues.

Recent childbirth, Torsion of GB

Cause Ischemia

Severely Ill Patients

Morphology

GROSS:

Size: The gallbladder is usually enlarged and tense, Color: bright red or blotchy, violaceous to green-black discoloration, imparted by subserosal hemorrhages.

Serosa : The serosal covering is frequently layered by fibrin and, in severe cases, by a definite suppurative, coagulated exudate.

Except for the presence or absence of calculi, the two forms of acute cholecystitis are morphologically similar.

Morphology

Gross: On cut section:

• Neck & Cystic duct: an obstructing stone is usually present

• LUMEN: Stones + Bile (cloudy or turbid bile that may contain large amounts of fibrin, pus, & hemorrhage).

• WALL: Thickened, edematous, and hyperemic.

• In more severe cases GB is transformed into a

green-black necrotic organ, termed Gangrenous cholecystitis, with small-to-large perforations.

• The invasion of GAS-FORMING ORGANISMS, notably clostridia and coliforms, may cause an acute “Emphysematous” cholecystitis.

• Mucosa: Bright Red, swollen.• When obstruction of the cystic duct is complete,

the lumen is filled with purulent exudate and the condition is known as EMPYEMA of the gallbladder.

MicroscopyThe inflammatory reactions are not distinctive and

consist of the usual patterns of acute inflammation:

Edema, Leukocytic infiltration, Vascular congestion, Frank abscess formation, or Gangrenous necrosis.

Clinical Features

•PAIN, fever, anorexia, tachycardia,

sweating, nausea, vomiting & mild jaundice.

• The pain may be referred pain that is felt in the right scapula rather than the right upper quadrant or epigastric region (Boas' sign). Phrenic Nerve

Boas's sign is hyperaesthesia (increased or altered sensitivity) below the right scapula .

The patients of acute cholecystitis of either type have similar clinical features.

with features of peritoneal irritation such as guarding and hyperaesthesia.

The gallbladder is tender and may be palpable.

Leucocytosis with neutrophilia

• PAIN may also correlate with eating greasy, fatty, or fried foods. CCK

• The Murphy sign is specific, but not sensitive for cholecystitis.

• Elderly patients and those with diabetes may have vague symptoms that may not include fever or localized tenderness.

Classically Murphy's sign is tested for during an abdominal examination; it is performed by asking the patient to breathe out and then gently placing the hand below the costal margin on the right side at the mid-clavicular line (the approximate location of the gallbladder). The patient is then instructed to inspire (breathe in). Normally, during inspiration, the abdominal contents are pushed downward as the diaphragm moves down (and lungs expand). If the patient stops breathing in (as the gallbladder is tender and, in moving downward, comes in contact with the examiner's fingers) and winces with a 'catch' in breath, the test is considered positive. In order for the test to be considered positive, the same maneuver must not elicit pain when performed on the left side. Ultrasound imaging can be used to ensure the hand is properly positioned over the gallbladder

Clinical features• More severe symptoms such as high fever, shock

and jaundice indicate the development of complications such as

•Abscess formation, •Perforation or •Ascending cholangitis.

• Another complication, gallstone ileus, occurs if the gallbladder perforates and forms a fistula with the nearby small bowel, leading to symptoms of intestinal obstruction.

Ileus is a disruption of the normal propulsive ability of the gastrointestinal tract. It is caused by failure of peristalsis i.e. non-mechanical obstruction.

• Clinical symptoms of acute acalculous cholecystitis tend to be more insidious, since symptoms are obscured by the underlying conditions precipitating the attacks.

• As a result of either delay in diagnosis or the disease itself, the incidence of gangrene and

perforation is much higher in acalculous than in calculous cholecystitis.

Early cholecystectomy within the first three days has a mortality of less than 0.5% and risk of complications such as perforation, biliary fistula, recurrent attacks and adhesions is avoided. However, medical treatment brings about resolution in a fairly large proportion of cases though chances of recurrence of attack persist.

Chronic cholecystitis is the commonest type of clinical gallbladder disease. There is almost constant association of chronic cholecystitis with cholelithiasis.

Chronic Cholecystitis • Chronic cholecystitis may be a sequel to repeated

bouts of mild to severe acute cholecystitis, • but in many instances it develops in the apparent

absence of ANTECEDENT attacks. • Since it is associated with CHOLELITHIASIS in more

than 90% of cases, the patient

populations are the same as those for gallstones.

90-95%

• Supersaturation of bile predisposes to both chronic inflammation and, in most

instances, stone formation.

• Unlike acute calculous cholecystitis, obstruction of gallbladder outflow is NOT a requisite.

• The symptoms of calculous chronic cholecystitis are biliary colic to indolent right upper quadrant pain & epigastric distress.

Pathogenesis

Pathogenesis

PathogenesisDystrophic Calcification: Porcelain Gallbladder

Morphology• Grossly, the gallbladder is generally CONTRACTED

but may be normal or enlarged.

Morphology• The morphologic changes in chronic cholecystitis

are extremely variable & sometimes minimal.

The serosa is usually smooth and glistening but may be dulled by subserosal fibrosis.

• Dense fibrous adhesions

• On sectioning, the WALL is variably thickened, and has an opaque gray-white APPEARANCE.

Serosa, Wall, Appearance, Lumen & Mucosa.

• In the uncomplicated case

• The LUMEN contains fairly clear, green-

yellow, mucoid BILE and usually STONES.

• The MUCOSA itself is generally preserved?.

Microscopy- Chronic cholecystitis

• In the mildest cases, only scattered LYMPHOCYTES, PLASMA CELLS, & MACROPHAGES are found in the mucosa and in the subserosal fibrous tissue.

• In more advanced cases there is marked

subepithelial and subserosal FIBROSIS, accompanied by MONONUCLEAR CELL INFILTRATION.

CHRONIC INFLAMMATION

• Outpouchings of the mucosal epithelium through the wall

(Rokitansky-Aschoff sinuses) may be quite prominent.

Rokitansky–Aschoff sinuses, also entrapped epithelial crypts, are pseudodiverticula or pockets in the wall of the gallbladder. Histologically they are outpouchings of gallbladder mucosa into the gallbladder muscle layer and subserosal tissue.

They are not of themselves considered abnormal, but they can be associated with cholecystitis.

They form as a result of increased pressure in the gallbladder and recurrent damage to the wall of the gallbladder. They are associated with gallstones (cholelithiasis).

Carl Freiherr von Rokitansky and Ludwig AschoffGermans.

Outpouchings of gallbladder mucosa into the gallbladder muscle layer and subserosal tissue

Rokitansky-Aschoff sinusesEntrapped epithelial cryptsPpseudodiverticula

Pockets in the wall of the gallbladder

1.Mononuclear infiltrate: lymphocytes, plasma cells, macrophages. 2. Fibrosis 3. Hypertrophy of muscularis propria.4.Rokitansky- Ascoff sinuses

outpouchings of gallbladder mucosa into the gallbladder muscle layer and subserosal tissue

Rokitansky-Aschoff sinuses

Microscopy- HM• 1. Thickened and congested mucosa but

occasionally mucosa may be totally destroyed. • 2. Penetration of the mucosa deep into the wall of

the gallbladder up to muscularis layer to form Rokitansky- Aschoff’sinuses.

• 3. Variable degree of chronic inflammatory reaction, consisting of lymphocytes, plasma cells and macrophages, present in the lamina propria and subserosal layer.

• 4. Variable degree of fibrosis in the subserosal and subepithelial layers.

A few morphologic variants of chronic cholecystitis are considered below:

Cholecystitis glandularis, Porcelain gallbladder, Acute on chronic cholecystitis.• Cholecystitis glandularis:

when the mucosal folds fuse together due to inflammation and result in formation of crypts of epithelium buried in the gallbladder wall.

Acute superimposed on chronic cholecystitis

Superimposition of acute inflammatory changes implies acute exacerbation of an already chronically injured gallbladder.

Porcelain gallbladder• In rare instances extensive dystrophic

calcification

within the gallbladder wall may yield a porcelain

gallbladder, notable for a markedly increased incidence of associated CANCER.

Chinaware, Pottery, ceramicPorcelain GB: When the gallbladder wall is calcified and cracks like an egg-shell.

Dystrophic Calcification

Dystrophic Calcification

Clinical Features

Chronic cholecystitis has ill-defined and vague symptoms. Generally, the patient presents with abdominal distension or epigastric discomfort, especially after a fatty meal. There is a constant dullache in the right hypochondrium and epigastrium and tenderness over the right upper abdomen. Nausea and flatulence are common. Biliary colic may occasionally occur due to passage of stone into the bile ducts.

Xanthogranulomatous cholecystitis• is also a rare condition in which the gallbladder

has a massively thickened wall, is shrunken, nodular, and chronically inflamed with foci of necrosis and hemorrhage.

Strawberry gallbladder, more formally cholesterolosis of the gallbladder, is a change in the gallbladder wall due to excess cholesterol

CHOLESTEROLOSIS

Hydrops of the gallbladder

• Finally, an atrophic, chronically obstructed gallbladder may contain only clear secretions , a condition known as hydrops of the gallbladder.

.Hydrops is the excessive accumulation of serous fluid in tissues or cavities of the body.