Pathology of the Gall Bladder and Exocrine Pancreas

Question 1

Gallstones (Choleliths)

Answer 1

associated with gallbladder inflammation (cholecystitis): causes 9 out of 10 cases of acute cholecystitis

major cause of pancreas inflammation (pancreatitis): causes 4 out of 10 cases of acute pancreatitis

Question 2

Cholesterol vs pigment stones

Answer 2

Cholesterol Stones (80%):
- Ethnicity: U.S.; North Europe;
			 Native Americans
- Advancing age
- Female sex hormones
	Female gender
	Oral contraceptives
	Pregnancy
- Obesity
- Rapid weight loss

Pigment stones (20%):

• Ethnicity: Asian; rural
• Chronic hemolytic syndromes
• Biliary infection
• Ileal disease

Question 3

Gallstone ileus

Answer 3

Pass from gallbladder into ileus from either bile duct or through an erosion and fistula

Question 4

Cholesterol gallstone formation

Answer 4

Cholesterol supersaturation in bile (increased cholesterol output into bile commonly or less commonly decreased bile acid synthesis) and subsequent crystallization

Promoted by gallbladder hypomotility and/or excessive mucus

Growth is about 2 mm/year

Question 5

Cholecystitis

Answer 5

Inflammation of the gallbladder

Acute vs chronic

Calculous vs acalculous

90% due to gallstone obstruction of the neck / cystic duct

other less common causes:

	- trauma
	- major surgery
	- severe burns
	- postpartum

Question 6

Acute cholecystitis symptoms

Answer 6

RUQ Pain
fever
Leukocytosis

Question 7

Acute calculous cholecystitis pathogenesis

Answer 7

Caused not just by obstruction but by accumulation of toxic products in lumen and disruption of protective mucus layer

Get distension of wall of gallbladder, ischemia (due to increased pressure on blood vessels in wall), and more inflammation

Question 8

Chronic Cholecystitis

Answer 8

Histopathologic term for inflammation and fibrosis of the gallbladder with poor correlation to clinical symptoms

Pathogenesis is not well established but 95% are associated with gallstones

Possible pathogenesis (theories): 
1. Recurrent attacks of mild acute cholecystitis (but most pt histories don't support this)

2. Repetitive mucosal trauma from gallstones (poor correlation with volume of gallstones)
3. Genetics of bile composition or inflammatory response (but no supporting evidence)

Question 9

Microscopic findings with acute calculous cholecystitis

Answer 9

Inflammatory destruction of mucosa

Erosion with inflammatory cells

Question 10

Gross findings in chronic cholecystitis

Answer 10

Firmness of gallbladder wall
95% of time have gallstones
Trabeculations

Question 11

Microscopic findings in chronic cholecystitis

Answer 11

Wide spectrum
Fibrosis of wall
Thickening of muscular layer of wall
Mononuclear cell infiltrate in gallbladder mucosa
Bits of mucosa that herniate through muscular layer

Question 12

Carcinoma of the Gallbladder

Answer 12

rare – 0.5% of cancers

poor survival – 1% alive at 5 years

major risk factors

	- gallstones (70% have stones)
	- chronic infection

Almost all are adenocarcinomas

Question 13

Gallbladder adenocarcinomas microscopic findings

Answer 13

Infiltrative gland-forming neoplasm in gallbladder
Atypical cytology
Atypical and large nuclei
Vary in shape
Mitotic figures

Question 14

Choledocholithiasis

Answer 14

Stones (choledocholiths) within the biliary tree

Major cause of ascending cholangitis

Most (90%) came from gallbladder originally

Question 15

Choledochal Cyst

Answer 15

Congenital dilatation of the common bile duct

Can involve hepatic ducts and/or cystic ducts

Present with findings of biliary obstruction (like jaundice)

Question 16

Bile Duct Carcinoma

Answer 16

Very rare Nearly all are adenocarcinomas

Risk factors:

• choledochal cyst in older adults
• primary sclerosing cholangitis
• infections (liver flukes)
• ? cholelithiasis

Question 17

Pancreatitis

Answer 17

Inflammation of the pancreas (Acute vs Chronic)

Sequelae

	- Pseudocysts
	- Abscesses
	- Pancreatic insufficiency
	- Secondary diabetes

Question 18

Causes of acute pancreatitis

Answer 18

Gallstones (45%)
Alcohol (35%)
Other (20%)

Question 19

What is the pathogenesis for gallstones causing acute pancreatitis?

Answer 19

NOT simply mechanical obstruction

Increased intraductal pressure leads to leakage of enzyme-rich fluids (digestive enzymes) and tissue injury (recruits inflammatory cells), inflammation, edema, ischemia, and more tissue injury

Question 20

What is the pathogenesis for alcohol causing acute pancreatitis?

Answer 20

NOT simply toxic injury (may contribute some)

Alcohol stimulates secretion of digestive enzymes so that they accumulate in pancreatic ducts

Alcohol causes contraction of sphincter of Oddi which can cause some obstruction

Alcohol also causes defective packaging of enzymes so that they can be inappropriately activated

Another hypothesis: Exacerbations of underlying chronic pancreatitis

Question 21

Gross findings of acute pancreatitis

Answer 21

Necrosis (can be hemorrhagic) in various places
Yellowish areas of auto-digested areas of adipose tissue

Can have pseudocysts

Question 22

Microscopic findings of acute pancreatitis

Answer 22

Edematous non-necrotic pancreas and adjacent complete destruction of parenchyma and fibrin and neutrophilic infiltrate

Pseudocysts: don’t have true cyst lining (instead just fibrous tissue)

Question 23

Chronic Pancreatitis

Answer 23

Irreversible parenchymal destruction and fibrosis

Multiple causes:

- most common identifiable cause is alcohol abuse
- long-standing duct obstruction
- hereditary forms of pancreatitis
- large proportion (40%) are idiopathic

Question 24

Pathophysiology theories for chronic pancreatitis

Answer 24

chronic duct obstruction by concretions

abnormal pancreatic secretions plug ducts

direct toxic effects on acinar cells

inducing oxidative stress on acinar cells

necrosis-fibrosis

acinar cell necrosis and replacement by fibrous tissue

Question 25

Gross findings in chronic pancreatitis

Answer 25

Fibrous scarring

Atrophy

Question 26

Microscopic findings in chronic pancreatitis

Answer 26

Varying degrees of atrophy and fibrosis
Lobules with atrophy
Loss of acinar tissue

Question 27

Pancreatic Neoplasia

Answer 27

95% ductal adenocarcinoma

2% endocrine neoplasms

Question 28

Pancreatic Ductal Adenocarcioma

Answer 28

Gland-forming
4th leading cause of death from cancer in US
Dismal prognosis
5% 5-year survival

Question 29

Pancreatic endocrine neoplasms

Answer 29

Most clinically relevant tumors are:

- nonfunctional (is it producing hormone that causes a clinical syndrome? most do not)
- well-differentiated 

Behavior is difficult to predict based on appearance

Functional tumors (produces a hormone that causes a clinical syndrome)

- insulinoma 42%, (fainting episodes from    hypoglycemia)
- gastrinoma 24% (peptic ulcer disease; zollinger-ellison syndrome)
- glucagon 14%

Question 30

Gross findings in pancreatic ductal adenocarcioma

Answer 30

Mass forming-lesion in pancreas, scarred appearance; obstructs pancreatic duct or common bile duct or both

Dilatation of ducts can happen

Question 31

Microscopic findings in pancreatic ductal adenocarcioma

Answer 31

Malignant glands, infiltrative
Atypical cells (size and shape of nuclei)

Question 32

Gross findings with Pancreatic Endocrine Neoplasms

Answer 32

Very round, well-demarcated, fleshy tumor
Don’t usually cause ductal obstruction
No dilatation of ducts

Question 33

Microscopic findings with Pancreatic Endocrine Neoplasms

Answer 33

Well-defined usually
Endocrine appearance
Ribbon-like growth pattern
Regular, round nuclei