Gallbladder and Pancreas

Objectives:

  1. Pathophysiology and Clinical Presentation
    1. of Cholelithiasis (cystic duct obstruction)
    2. Acute and chronic Cholecystitis (inflammation of gallbladder)
  2. Pathophysiology of acute and chronic pancreatitis
  3. Pancreatic Tumours

 

Gallbladder

Tumours

  • Benign:
    • Cholelithiasis (cystic duct)
    • Cholecystitis (gallbladder)
  • Malignant:
    • Adenocarcinoma (cancer of glandular tissue epithelium)

Cholelithiasis (Gallstones)

In the west, 10-20% of population has cholelithiasis; 80% are asymptomatic

  • Cholesterol Stones
    • Bile is supersaturated with cholesterol
    • Risk factors:
      • Rapid Weight loss, Obesity, AgeF>M, gallbladder stasis (blocked route)
  • Pigment stones
    • Increased unconjugated (not broken down) bilirubin (from RBC breakdown) in bile
    • Risk factors:
      • Asian pop, chronic haemolysis, biliary infection

 

Clinical Presentation Complications
Biliary pain:

pain is in the right upper part of the abdomen, and it can radiate to the shoulder. Pain usually lasts from one to a few hours.
  1. Cholecystitis
  2. Cholangitis (inflammation of bile duct)
  3. Empyema (pus in the pleural cavity)
  4. Obstructive cholestasis
  5. Pancreatitis
  6. Perforation
  7. Fistula (abnormal connection)
  8. Gallstone ileus (small bowel obstruction)
  9. Carcinoma

 

Cholecystitis

Inflammation of the gallbladder

Acute Cholecystitis

Clinical Presentation
  1. Calculous
    1. Gallstone obstruction
  2. Acalculous
    1. inflammatory disease of the gallbladder without evidence of gallstones or cystic duct obstruction
    2. “Severe systemic illness”
  • RUQ (right upper quadrant)/ epigastric pain
  • Fever, tachycardia, N+V
  • Anorexia (decreased sensation of appetite)
  • 25% require immediate surgery (removal of gallstones)

Chronic Cholecystitis

Clinical Presentation
> 90% bear calculi (gallstones present)

characterized by repeated attacks of pain (biliary colic) that occur when gallstones periodically block the cystic duct.

Gallbladder is damaged by repeated attacks of acute inflammation, usually due to gallstones, and may become thick-walled, scarred, and small.
  • Recurrent RUQ/ epigastric pain, N+V, fat intolerance
  • Complications

Morphology:

Fibrosis;

Roktansky-Aschoff sinuses: (Histologically, they are outpouchings of gallbladder mucosa that sit within the gallbladder muscle layer)

Porcelain GB (calcification of the gallbladder)

Carcinoma (of gallbladder)
  • Uncommon, F>M, 7th decade
  • 60-90% gallstones
  • Unresectable – liver/ cystic duct
  • Fundus/ neck
  • Infiltrative/ exophytic (tending to grow outward beyond the surface epithelium from which it originates)
  • 95% adenocarcinoma
  • Sx – cholecystitis

 

Extrahepatic Bile Ducts

(small tubes that carry bile outside of the liver)

Congenital

Acquired
  • Biliary Atresia (narrowing)
    • destruction of extra+/-intrahepatic bile ducts in neonatal period
    • neonatal cholestasis (acholic stools)
  • Choledochal cyst (cystic dilatations of the biliary tree)
  • Choledocholithiasis
  • Ascending Cholangitis – secondary to duct obstruction
  • Carcinoma

 

 

Pancreas

Pancreatic Function

Exocrine

Ductal glands

Endocrine

Non-ductal glands
Production of:

  1. pH 7.5-8, NaHCO3
  2. Amylase
  3. Lipase
  4. Trypsinogen
  5. Chymotrypsinogen
 Production of:

  1. Insulin, Glucagon, Others

 

Pathologies (Abnormalities)

  1. Congenital anomalies
  2. Exocrine
    1. Acute pancreatitis
    2. Chronic pancreatitis
    3. Autoimmune pancreatitis
    4. Cystic fibrosis (lack of cl- transport = lack of water = thickened mucus)
  3. Endocrine
    1. Diabetes mellitus (insulin)
  4. Tumours
  1. Congenital Anomalies
Pancreas divisum

congenital anomaly in the anatomy of the ducts of the pancreas in which a single pancreatic duct is not formed, but rather remains as two distinct dorsal and ventral ducts.

 Annular pancreas

second part of the duodenum is surrounded by a ring of pancreatic tissue continuous with the head of the pancreas.

This portion of the pancreas can constrict the duodenum and block or impair the flow of food to the rest of the intestines.

2. (a) Acute Pancreatitis

Common: 10-20/ 100,000; Biliary tract disease

Causes:

  1. Alcohol (main)
  2. Pancreatic duct obstruction (gallstones etc.)
  3. Medications
  4. Infection – mumps
  5. Metabolic – ↑ Ca++
  6. Acute ischaemia
  7. Trauma
  8. Genetic

 

Severe Pancreatitis:

Clinical Features

Complications
  1. Abdominal pain, radiating to back
  2. Systemic: release of toxic enzymes, cytokines into circulation – haemolysis, fluid sequestration, DIC, ARDS, shock, ARF (ATN)
  3. Laboratory
    1. ↑ amylase, lipase; ↓ Ca2+ poor prognosis
  4. Management – NPO
  1. Shock : death in 10%
  2. Recurrent attacks : chronic pancreatitis
  3. Pseudocyst

 

2. (b) Chronic Pancreatitis

Result of longstanding damage to the pancreas

 

Aetiology

Chronic Pancreatitis

  1. Alcohol (75%)
  2. Biliary disease (1%)
  3. Following acute pancreatitis
  4. Chronic protein malnutrition (Africa, Southeast Asia)
  5. Autoimmune Pancreatitis, AIP

Presentation

Chronic Pancreatitis

  1. Abdominal pain
  2. Calcification : calculi
  3. Exocrine insufficiency : steatorrhoea, wasting
  4. Diabetes mellitus
  5. Pseudocyst +/- cyst rupture

2. (c) Autoimmune Pancreatitis
  • IgG4: blood and tissue
  • Systemic disease
  • Salivary glands (Sjogren’s-like)
  • Retroperitoneal fibrosis
  • Riedl’s thyroiditis
  • PSC-like biliary strictures
  • Diff = Carcinoma

Pseudocyst

a fluid-filled cavity resembling a cyst but lacking a wall or lining

  • Localised collection of necrotic – haemorrhagic material devoid of epithelial lining
  • Usually solitary
  • Substance of gland or peripancreatic soft tissue – lesser sac/ retroperitoneum/ between stomach and liver
  • Outcome:
  • Resolve/ 20 infxn/ compress or perforate into adj structures

 

2. (d) Cystic Fibrosis

Autosomal recessive (Chromosome 7)

  • 4% carriers
  • Cystic fibrosis transmembrane conductance regulator (CFTR)

3. Exocrine: Diabetes Mellitus

  1. Type I
    1. Absolute deficiency of insulin due to β cell destruction – Autoimmune – HLA D
  2. Type II
    1. Combination of peripheral insulin resistance & inadequate pancreatic response – Obesity
  3. Other
    1. Genetic, exocrine pancreatic disease, endocrinopathies, infection, drugs

Morphology

Diabetes Mellitus

Pancreatic changes variable/ not necessarily dramatic

  • Type I
    • Reduced no. & size of islets
    • Insulitis
  • Type II
    • Amyloid deposition in islets

4. Pancreatic Neoplasia (cancer)

  • Tumours of Exocrine pancreas (>90%):-
    • Ductal adenocarcinoma
    • Mucinous cystic neoplasms
    • Intraductal papillary mucinous tumours

Rare : pancreaticoblastoma (children) , solid psuedopapillary neoplasm (women, mean age 30yrs)

    • Endocrine Tumours (5-8%)
      • Basic & Multiple Endocrine neoplasia
    • (a) Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma is a type of exocrine pancreatic cancer. It develops from cells lining small tubes in the pancreas called ducts. PDAC can grow anywhere in the pancreas, although it is most often found in the head of the pancreas.

  • In Ireland: 404/ year

Incidence rate: F 8.84, M 10.34,

  • usually age 60-80
  • 5 year survival < 5%
  • Disseminate early
 Precursor: PanIN (type of epithelial lesion)

Molecular carcinogenesis: (altered genes)

  • K-ras, p16, SMAD4, p53

Aetiology:

  • Smoking (Chronic pancreatitis, DM)
Familial in 10% of cases:-

  • BRCA2
  • FAMM (familial atypical multiple mole-melanoma) (p16 mutation)
  • Peutz-Jeghers Syndrome (STK11/LKB1 mutation)
  • Familial pancreatitis (PRSS1 mutation)
  • HNPCC (msimatch repair mutation)
  • Fanconi’s anaemia (FANc-C, FANc-g mutation)
 Clinical Features

  • Pain
  • Obstructive jaundice
  • Weight loss, anorexia, malaise, weakness
  • Migratory thromobophlebitis – Trousseau sign

Course: Brief, progressive

  • <20% resectable

(if resectable – Whipple’s procedure )

Whipple’s Procedure

(b) Mucinous Cystic Neoplasm

    1. Almost exclusively seen in females in fifth – sixth decade
    2. Almost always located in the tail of pancreas
    3. May be amenable to surgical resection

(c) Intraductal Papillary Mucinous Neoplasm

    1. 5% of all pancreatic tumours, 7th-8th decade
    2. Mucin deposition within ducts, which become cystically dilated
    3. Gives distinctive radiological appearance
    4. Amenable to surgical resection

2. Endocrine Neoplasm

      • 2% of pancreatic tumours
      • Behaviour difficult to predict ( size, mitotic activity, functionality)
        • Functional = produces hormones (affect activity)
        • Non-functional = no production

Functional

Presentation
Usually indolent clinical course (benign)

  • Insulinoma
  • hypoglycaemic attacks
More Aggressive Tumours:

  • Glucagonoma
  • diabetes

May produce more than one hormone
  • VIPoma
  • severe, chronic watery diarrhoea
  • Gastrinoma
  • Zollinger-Ellison Syndrome (severe peptic ulceration)

Multiple Endocrine Neoplasia

inherited disorders in which several endocrine glands develop noncancerous (benign) or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by gene mutations, so they tend to run in families.

      • Group of familial syndromes associated with hyperplasia or neoplasia of several endocrine organs
        • Consider in patients with endocrine tumour – ? family history
      • MEN I – Parathyroid hyperplasia , pituitary, pancreatic tumours

 

 

Summary

Objectives:

      1. Pathophysiology and Clinical Presentation
        1. of Cholelithiasis (cystic duct obstruction)
        2. Acute and chronic Cholecystitis (inflammation of gallbladder)
      2. Pathophysiology of acute and chronic pancreatitis
      3. Pancreatic Tumours

What are the histological features of each of the diseases?