Path Notes: Cholelithiasis***** (gall stones in gallbladder)

Question 1

What is Cholelithiasis? Describe the epidemiology:

Answer 1

Cholelithiasis = gall stones in gallbladder

Common - affecting 10-20% of adult population in Western Countries

Most (80%) are silent

Question 2

What are the types of stones?

Answer 2

1. Cholesterol stones - account for 80% in the Western world. Contain >50% crystalline cholesterol monohydrate
2. Pigment stones - composed predominantly of bilirubin calcium salts

Question 3

What are the key risk factors for cholesterol stones?

Answer 3

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1. Fair skin - more common amongst ‘fair-skinned’ ethnic groups, in western countries
2. Forty (increasing age)
3. Female (2:1)
4. Fertile (Oestrogens-OCP and pregnancy increase expression of lipoprotein receptors and increase cholesterol uptake; also stimulate HNG-CoA reductase which increases biosynthesis of cholesterol)
5. Fat (associated with obesity and rapid weight loss)

Question 4

What is associated with acquired cholelithiasis?

Answer 4

gall bladder stasis

Question 5

What is associated with hereditary cholelithiasis?

Answer 5

leads to less absorbed cholesterol, and increased production of cholesterol

Question 6

Describe Cholesterol Stones?

Also describe pathogenesis

Answer 6

Cholesterol monohydrate crystals that aggregate to form stones

10-20% of cholesterol stones are radio-opaique (because they have sufficient calcium carbonate)

Cholesterol is rendered soluble by:

• Bile
• Water-soluble bile salts
• Water-insoluble lecithins

(the former two acts as detergents)

1. Stones occur when cholesterol concentrations exceed the solubilising capacity - supersaturation
2. Cholesterol can no longer remain dispersed by the detergents, and forms solid cholesterol monohydrate crystals
3. Free cholesterol is toxic to the gallbladder, and penetrates the wall, leading to gall bladder hypomobility
4. There then subequent hypersecretion of mucous within the gallbladder, which traps the crystals, permitting their aggregation into stones

Question 7

Describe Pigment Stones

Answer 7

Composed of bilorubin calcium salts

Choleserol hypersecretion by hepatocytes within the liver promotes excessive cholesterol ester accumulation within the lamina propria of the gallbladder

This causes the gallbladder’s mucosal surface to be studded with multiply minute yellow flecks - strawberry gallblader

Question 8

Describe the Clinical Presentation of Gallstones

Answer 8

May be asymptomatic - these are called ‘silent stones’ and don’t need to be treated

Colicky / constant pain due to the obstructive nature of the stones in RUQ

Pain may radiate between the shoulder blades or below R shoulder

Typically worse after fatty meals and alcohol

Thus often occurs at night

Thus patient may present with a bit of weight loss if they have been avoiding fatty meals or meals altogether

Murphy’s sign is positive*

Question 9

What are some key complications of gall stones?

Answer 9

Biliary Colic

Acute Cholecystitis

Chronic Cholecystitis

Choledocholithliasis

(In association with the above / complications of the above - Empyema, perforation, fistula, cholangitis, obstructive jaundice, gallstone ileus, increased risk of cancer in the gallbladder)

Question 10

What is Cholecystitis?

Answer 10

Inflammation of the gallbladder, which may be acute, chronic, or acute on chronic

Almost always associated with gall stones

Question 11

Describe Acute Cholecystitis, and the two types

Answer 11

Acute inflammation of the gall bladder

1. Acute Calculous Cholecystitis:
   - Accounts for 90% of Acute Cholecystitis
   - Usually precipitated (90% of the time) by obstruction of the neck of the gallbladder or cystic duct
2. Acute Acalculous cholescystitic
   - Accounts for 10%
   - Occurs in severely ill patients

Question 12

Describe the Pathogenesis of Acute Calculous Cholecystitis:

Answer 12

1. Irritation and inflammation of the obstructed gallbladder
2. Accumulation of bile and other products within the gallbladder leads to:
   - Disruption of mucosal layer
   - Release of prostaglandins that contribute to mucosal and mural inflammation
3. Results in gall-bladder dysmobility, increased luminal pressure, and compromised blood flow

More complicated version - probs don’t need to know???

(((2. Actions of mucosal phospholipases hydrolyze the luminal lecithins to toxic lysolecthins that disrupt the protective mucosal layer

3. Detergent action of bile salts
4. Prostaglandins released within will contribute to mucosal and mural inflammation )))

Question 13

Describe the Pathogenesis of Acute Acalculous Cholecystitis:

Answer 13

Occurs in severely ill, thus risk factors include:

1. Sepsis with hypotension
2. Multi-system organ failure
3. Immunosuppression
4. Major trauma and burns
5. Diabetes
6. Infections

Pathogenesis likely involves ischaemia, as the cystic artery is an end artery

Question 14

Describe the macroscopic features of Cholecystitis:

Answer 14

1. Enlarged, tense GB
2. Bright red and blotchy
3. Violety/green/black discoloration is imparted by subserosal haemorrgahes
4. Fibrin, and in severe cases, suppurative exudate
5. Cloudy or turbid bile that may contain large amounts of fibrin, pus and haemorrhage (if purely pus, then is Empyema)

In mild cases:

• Gall bladder wall thickening with hyperaemia
• Due to oedema

In severe cases:

• Gangrenous cholecystitis
• With small-large perforations

Question 15

Describe the Microscopic appearance of Cholecystitis

Answer 15

1. Oedema
2. Leukocyte infiltration
3. Vascular congestion
4. In severe cases:
   - Flank abscess formation
   - Gangrenous necrosis

Question 16

Describe the clinical presentation of an individual with Cholecystitis:

Answer 16

1. RUQ / epigastric pain
2. Mild fever
3. Tachycardia
4. Anorexia
5. Sweating
6. Nausea and Vomiting

• May be sudden onset
• May require urgent surgery, or may resolve

Resolution occurs within 7-10 days, and frequently within 24 hours

*25% of cases develop more serious symptoms, requiring immediate surgery

**Higher incidence of gangrene occurs in Acalculous cholecystitis (because is typically associated with cholecystitis due to ischaemia secondary to other serious condition)

Question 17

What is chronic cholecystitis?

Answer 17

May be a secondary or repeated bout of mild-severe acute cholecystitis

Associated with cholelithiasis in over 90% of cases

Question 18

Describe the pathogenesis of chronic cholecystitis:

Answer 18

Unsure of exact pathogenesis

Likely to occur due to the supersaturated bile predisposing to both chronic inflammation and stone formation

Complete obstruction to outflow of bile is not a requisite*

Microbial organisms can be cultured in ~1/3 of cases - E.coli or enterocoli

Question 19

Describe the macroscopic features of chronic cholecystitis:

Answer 19

Serosal membrane changes vary:

• Dull and fibrotic
• Smooth and glistening

Fibrous adhesions can occur

GB wall is variably thickened

Wall has opaque/grey appearance

Reduced wall flexibility

Question 20

Describe the microscopic features of chronic cholecystitis:

Answer 20

1. variable degrees of inflammation may be present
2. Lymphocytes, plasma cells and macrophages are found in the mucosa and sub-serosal fibrous tissue
3. Reactive proliferation of the GB mucosa may give rise to buried pits of epithelium in the wall
4. Outpouching of the epithelium into the muscular layer and sub-serosal tissue = entrapped epithelial crypts

Rarely, dystrophic calcific-porcelain gallbladder develops - associated with increased risk of cancer

Question 21

What is Xanthogranulomatous Cholecystitis?

Answer 21

Rare condition

1. Shrunken, nodular and chronically inflamed galbladder
2. Foci of haemorrhage and necrosis
3. Gallstones are usually present
4. Rarely, ‘porcelain gallbladder’ develops - condition where gallbladder calcifies. This is associated with increased risk of cacer

Question 22

Describe the clinical presentation of an individual with chronic cholecystitis:

Answer 22

1. Recurrent attacks of colicky or steady RUQ pain
2. +/- nausea and vomiting
3. Intolerance (due to episodes) for fatty foods and alcohol (potentially)

Question 23

Describe some of the main complications of acute and chronic cholecystitis:

Answer 23

1. Cholangitis or sepsis - bacterial infection
2. Perforation causing local abscess formation
3. Rupture with peritonitis
4. Biliary-enteric fistula, with entry of air and bacteria into the biliary tree, and gallstone ileus
5. Aggravation of pre-existing illness
6. Porcelain gallbladder

Question 24

What is choledocholithiasis?

Answer 24

Presence of gall stones within the bile ducts of the biliary tree

Question 25

What is cholangitis? Most common cause?

Answer 25

Cholangitis is the term used to describe bacterial infection of the bile ducts, most commonly secondarily to obstruction by gallstones and strictures, leading to stasis

Question 26

What is ascending cholangitis?

Answer 26

Ascending cholangitis is bacterial infection of the intra-hepatic biliary ducts

Question 27

Common pathogens involved in ascending cholangitis?

Answer 27

E. coli
Klebsiella
Clostridium
Bacteriodes
Enterobacter
Group D Streptococci

Question 28

Describe the clinical presentation of ascending cholangitis

Answer 28

1. Fever
2. RUQ pain
3. Jaundice

Tend to look (because they are) very unwell
Life threatening condition