PANCREAS AND GALLBLADDER

Emma E. Furth, M.D.

A. PANCREAS

I. NORMAL STRUCTURE & FUNCTION: EXOCRINE & ENDOCRINE

A. FUNCTION

1. Exocrine: Secretes lipase's and protease's which break down proteins and lipids as a necessary step for their subsequent absorption.
2. Endocrine: Islets secrete insulin for glucose control

B. GROSS ANATOMY AND DUCTAL CONNECTION

The pancreas is located in the retroperitoneum and weighs 100g. The "head" is embedded into the first portion of the duodenum and preceded by the body and tail. The pancreatic ductal system is composed of the main duct with occasional persistence of the proximal portion of the dorsal duct (duct of Santorini). 2/3 of people have the common bile duct fuse with the pancreatic duct and drain via the ampule of vater. The pancreas is not bound by a capsule and is surrounded by fat. On cut surface it appears yellow and lobulated.

C. HISTOLOGY

1. Exocrine

Acinar cells are arranged in groups and feed into the minor ducts which feed into the main duct. The ducts are lined by glandular epithelium. The acinar cells contain the digestive enzymes.

2. Endocrine

The islets are composed of neuroendocrine cells each of which secretes a specific hormone(insulin,glucagon,pancreatic polypeptide). Islets are most concentrated in the tail.

II. CONGENITAL ABNORMALITIES

A. ECTOPIC

Usually exocrine pancreas found in 2% of population. Found in stomach and duodenum mostly followed by jejunum, Meckel's and ileum.

B. PANCREATIC DIVISUM

There is a failure of fusion of the ventral and dorsal ducts resulting in a dual duct system. There is controversy about its association with pancreatitis.

III. ACUTE PANCREATITIS

A. DEFINITION

An acute condition with marked serologic elevation of amylase and lipase presenting with abdominal pain.

B. HISTOLOGY AND PATHOPHYSIOLOGY

1. There is a release of activated pancreatic enzymes into the pancreatic parenchyma (see below for enacting conditions)
2. Subsequent proteolysis and lipolysis ensues
3. As a result, inflammation, hemorrhage, fat necrosis occurs. The fat necrosis can be seen grossly as chalky areas.

C. CLINICAL OUTCOME

1. Short term: Disseminated intravascular coagulation, pain, hypotension,acute respiratory distress. If severe enough death may occur.
2. Longer term: Pancreatic abscess, pseudocyst
3. Repeated episodes of acute pancreatitis may lead to chronic pancreatitis.

D. ENCITING CONDITIONS

1. Gallstones

most common. Women> men. Peak 50- 60 years old.

2. pancreatic carcinoma

3% of time presents with acute pancreatitis.

3. RARE:

choledochal cyst, parasites, (however, in Kashmir India ascariasis is the most common cause of pancreatitis). Pancreatic divism is debated as a cause.

4. Drugs

1. ETHANOL
2. azathioprine

5. toxins

1. scorpion venom, organophosphates

6. Trauma

1. iatrogenic, i.e. post ERCP
2. abdominal

7. Metabolic

1. hypertriglyceridemia (>1000mg/dl; type V)
2. hypercalcemia

8. Infection

1. viral: mumps, coxsackie, CMV, hepatitis A,B,C. Some bacteria.

9. Rare: penetrating duodenal ulcer, Crohn's

10. Idiopathic

IV. CHRONIC PANCREATITIS

A. DEFINITION

Repeated acute inflammatory insults result in fibrosis and loss of pancreatic parenchyma

B. HISTOLOGY AND PATHOPHYSIOLOGY

Repeated acute inflammatory attacks leads to chronic pancreatitis. Grossly, the pancreas is hard due to fibrosis with areas representing calcifications which may be harder. There is atrophy ie loss of the acinar cells with relative preservation of the islets. Eventually, the islets may be destroyed. There is a sparse lympocytic inflammatory infiltrate. The ducts may become structured in areas with dilatation in others.

C. CLINICAL OUTCOME

1. Exocrine pancreatic insufficiency: Malabsorptive diarrhea,malnutrition.
2. ONLY RARELY do the islets get destroyed: diabetes

V. CYSTIC FIBROSIS

CF patients may develop exocrine pancreatic insufficiency due to atrophy of acini. This atrophy is NOT associated with inflammation but is due to prolonged, small duct plugging with viscous mucous. CF patients due not usually develop acute or "chronic" pancreatitis.

VI. TUMORS

Pathology is of paramount importance in diagnosing and giving prognostic outcome in these tumors. Again any cell which is present may become malignant. Metastatic tumors to the parenchyma of the pancreas are RARE. However mets to the ampulla are possible (renal cell).

A. PANCREATIC ADENOCARCINOMA

These tumors represent the majority (75-92%) of pancreatic neoplasias and are an adenocarcinoma. These tumors arise from ductal epithelium and most likely proceed through a dysplasia carcinoma sequence. These tumors usually start in head of pancreas and causes obstruction of ampulla leading to painless jaundice. Risk factors include smoking, exposure to carcinogens, and high fat diet. These tumors usually have dismal prognosis as they present at a high stage.
The tumor infiltrates in small, angulated glands with a tremendous desmoplastic (i.e. collagen) reaction.

B. MUCINOUS CYSTIC adenoma/carcinoma/biliary cystadenoma:

Of ductal epithelial origin. Presents with unit or multilobulated cyst. May or may not cause vague symptoms. Needs to be excised in its entirety. Biliary cystadenoma have OVARIAN stroma and occur only in women. Prognosis of these lesions depends on presence or absence of invasion and extent thereof. Distinguish from pseudotumors.
QUESTION: WHAT ARE THE DIFFERENCES BETWEEN A PSEUDOTUMOR AND A MUCINOUS CYSTADENOMA?
If there is invasion then the tumor is a cystadenocarcinoma.

C. ISLET CELL TUMOR/NEUROENDOCRINE TUMOR

Neuroendocrine cell origin. May or may not produce hormones and cause symptoms. Some may secrete insulin leading to hypoglycemia. Tail preference (makes sense - there are more islets in the tail than the head!) See G.I. lecture. These are low grade carcinomas which may metastasize and Kill.

D. ACINIC CELL TUMOR

Rare tumor from acinic cell.

E. OTHERS

B. GALLBLADDER AND EXTRAHEPATIC BILIARY SYSTEM

I. NORMAL STRUCTURE AND FUNCTION

A. GROSS ANATOMY AND DUCTAL CONNECTION

The gallbladder serves as a reservoir of bile and is connected to the liver by the cystic duct and to the ampule of vater via the common bile duct.In 60-70% of people the common bile duct joins directly the pancreatic duct before entering the ampule of vater. In the remaining population the duct runs parallel to the pancreatic duct in the ampula. There is a variant of normal called "strawberry gallbladder" which has cholesterol laden macrophages in the mucosa.

B. HISTOLOGY

Unlike the other tubal parts of the GI tract, the gallbladder consists only of a mucosal, fibromuscular, and serosal layers. The mucosa is composed of glandular biliary type epithelium which arborizes.

C. FUNCTION AND REGULATION

The gallbladder stores bile until cholysistikinin stimulates contraction and emptying.

II. CONGENITAL ABNORMALITIES

A. GALLBLADDER

Abnormalities are rare but the most common, which at times causes the surgeon to be concerned when he or she palpates it, is the "phrygian cap". This abnormality is benign and is an admixture of glands and muscle (adenomyoma) forming a mass at the tip of the fundus.

B. EXTRAHEPATIC BILIARY DUCTS

The most common congenital abnormality is choledocal cysts which are diverticuli of the ducts. These may cause extrahepatic biliary obstruction and have an increased risk of developing cholangiocarcinoma. Histologically they are composed of all the normal components of the biliary duct as they are true diverticulum. A small percentage of biliary atresia cases are though to be congenital. (see Lecture #4)

III. CHOLELITHIASIS AND CHOLECYSTITIS

A. DEFINITION AND ETIOLOGY

1. cholelithiasis=gallstones; cholecystitis=inflammation.
2. Gallstones

a. Affect 10-20% of adult population. The majority of stones are asymptomatic and are usually mixed cholesterol/bile in composition.

b. Predisposing factors

1. Cholesterol stones: Northern European, Native American, South American, Mexican. Female,age,obesity,stasis.

2. Bilirubin stones: Hemolytic states, biliary infection, Asian, ileal disease(i.e. Crohn's), pregnancy

B. TYPES OF CHOLECYSTITIS

1. Acute and chronic due to stones

This is the most common form. Neutrophilic and lymphocytic infiltration in mucosa and wall. With chronicity there may be fibrosis and subsequent wall thickening. Invaginations of glands into the wall result in Rokitansky-Aschoff sinuses.

2. Acalculous

Usually occurs in debilitated patients most likely due to ischemia. Stones may or may not be found. The gallbladder is gangrenous.

C. PRESENTATION

Acute upper right quadrant abdominal pain which may radiate to back.

D. COMPLICATIONS

1. Pain, peritonitis if severe, ascending cholangitis.

2. "Gallstone ileus": a rare presentation where the gallstone erodes into the duodenum creating a direct entrance of bowel gas into the biliary tree (hence, air found on plain film in biliary system). The stone may cause obstruction at the ileal cecal valve.

IV. TUMORS

A. CARCINOMAS/CHOLANGIOCARCINOMAS

1. Just as in the rest of the GI tract, the adenoma-carcinoma sequence is followed.

2. Histology

Dysplastic surface glands may be found and at times form a polyp. Infiltrate as adenocarcinoma.

3. Predisposing factors

a. Chronic inflammation due to stones, infections including parasites

b. Porcelain Gallbladder: Calcifications in wall. May be seen on plain film x-ray. Etiology unknown.

c. Native American with stones

4. Klatskin tumor

These cholangiocarcinomas arise at the junction of the left and right hepatic biliary duct and thus present with biliary obstruction. Bad prognosis.

B. OTHERS

Always consider metastatic disease; melanoma is the most common metastatic disease to the gallbladder. Other primary tumors may arise such as lymphoma, sarcomas but are rare.