A. Pear shaped, 50 cc capacity, fundus, body, neck

a. 5-10x concentration capacity

b. Not essential for normal function

c. Neck narrows into cystic duct which joins hepatic duct to form the common bile duct.  Pancreatic duct and common bile duct drain into Ampulla of Vater in 2/3 of individuals, 1/3 individuals have parallel ducts.

a. Mucosa

·        Single lining of columnar cells

·         No muscularis mucosae

b. Fibromuscular layer

c. Subserosa

·         Fat, vessels and nerves

d. Serosa

·         Pritoneum – not present on hepatic sufrace

 bicarbonate fluid mixture composed of

• bile salts(cholates, chenodeoxycholates, and deoxycholates, etc.
• phospholipids (lecithin), and
• cholesterol
• lesser fraction of protein and bilirubin. 
• Function-acts as detergent to emulsify     nutrient fat. 

• circulation
  1. terminal ileum
  2. portal blood
  3. liver
• function- reabsorb 95% of bile salts (if fecal loss of bile salts, represents loss of cholesterol)

gallstones

• cholesterol stones (majority) (aka crystallized cholesterol)
• pigmented stones (aka bilirubin calcium salts)

·         Ethnic/genetic and geographic

a. Native Americans,

industrialized societies

·         Age and sex

a. increasing with age

b. Females predominance

·         Hereditary factors

a. Hereditary anemias with hemolysis

b. Inborn errors of bile salt synthesis / secretion

c. Inborn errors of lipid transportation

·         Environmental factors

a. diet and obesity

b. hormonal (pregnancy, estrogens, contraceptives)

c. disease states (hypothyroidism, nephrotic syndrome, Crohn’s disease with ileal disease or resection, cystic fibrosis). 

d. Risk factors for pigmented stones include chronic hemolytic syndromes, biliary infections, and gastro-intestinal diseases.

1. abnormal bile composition with supersaturated excess cholesterol to bile salt/phospholipid ratio,

·         excess unconjugated bilirubin, lithogenic bile may result from decrease bile salt synthesis, increase bile salt loss or increase cholesterol synthesis/ secretion

2. nucleation by microprecipitates (mucus, sloughed cells, bacteria, etc.) promoted by hypomotility and mucus hypersecretion

3. aggregation and growth favored by increased residence time and bile stasis.

•  None, » 80% of persons with gallstones are asymptomatic,
• Inflammatory and obstructive diseases
  • biliary colic and cholecystitis
  • ascending cholangitis
  • acute pancreatitis
  • “gallstone ileus”
• Malignancy <1% with history of cholelithiasis in individuals over 60 years, but >90% of gallbladder carcinoma associated with gallstones.

• definition- gallstones in the biliary tree
  • may pass from gallbladder or form in the biliary tree and lodge in cystic duct
• complications
  • jaundice
  • acute pancreatitis
  • ascending cholangitis

• definition- Acute inflammation of the gallbladder in the setting of gallstones with obstruction of neck or cystic duct (90% of acute cholecystitis cases)
• Pathogenesis
  • obstruction →
  • bile chemical irritation →
  • release of prostaglandins / distension →
  • compromise of blood flow to mucosa, ischemia →
  • mucosal erosion/ulceration,               
• Complications
  • bacterial superinfection
  • cholangitis
  • perforation with abscess or peritonitis
  • biliary-enteric fistula
• tx- cholecystectomy

• Histology
  • Frequently ulcerated or denuded mucosa
  • edema
  • numerous neutrophils
  • abscess formation
  • gangrene.
• Gross
  • Distended, violaceous or bright red
  • exudate on serosal surface.
  • wall is thickened and friable

• defintion- inflammation of the gallbladder in the absence of gallstones (10% of cases)
• clinical situations
  • setting of multiorgan disease syndrome (sepsis, burns, trauma, or major surgery) and ischemia of the cystic artery. 
  • patients with AIDS, infection with CMV and cryptosporidiosis, or in 
  • vasculitis
  • diabetes mellitus

• Most commonly associated with
  • gallstones
  • frequently showing features of combined acute and chronic inflammation. 
• Gross
  • Variable from near normal looking to markedly thickened wall.
  • Mucosa may be atrophic/ denuded.
• Microscopic
  • Flattened / denuded epithelium or hypertrophy;
  • prominent Rokitansky - Ashoff sinuses
  • lymphocytic infiltrate
• Comlications
  • hydrops
  • porcelain gallbladder
  • rarely carcinoma

·         Frequently associated with gallstones (60-90%)

·         Most commonly adenocarcinomas

·         Rarely discovered at a respectable stage

·         Elderly individuals.

·         Most common sites: fundus and neck

·         Gross: fungating (well defined mass), or infiltrating, (diffuse thickening of the wall) 

·         Poor prognosis

·         most common sites: common bile duct >junction of ducts >hepatic duct >cystic duct.

·         Usually, adenocarcinoma with early invasion and metastases prevents resection, poor survival.

• Combined exocrine/endocrine organ; bulk of parenchyma is exocrine with endocrine islets (langerhans)
• Located in retroperitoneum
• 2/3 adults have their major duct join the common bile duct before the ampulla of Vater forming a common channel for pancreatic and biliary drainage.
• Pancreas secretes 2-3 liters per day of an alkaline enzyme-rich fluid.  The organ is protected from self-digestion due to the protease inhibitors within the secretion and enzymes secreted as inactive precursors packaged within zymogen granules.

• genetics
  • autosomal recessive
  • CFTR gene (acts as cAMP regulator on chromsome 7 mutated
• dx- positive chloride sweat test
  • increased Cl conc. in sweat
  • increased Na conc. in sweat
• epidemiology
  • mostly whites
  • most common cause of chronic pulmonary disease (outside of TB) in children (comes with pancreatic deficiency)

• Pathology related to abnormal mucus secretions leading to obstruction and secondary damage
• Pancreatic obstruction leads to acinar atrophy and insufficiency with maldigestion, malabsorption, and steatorrhea
• Bronchial mucus obstruction produces mucopurulent secretions with bronchopneumonia, bronchiectasis and lung abscesses (Staph. and Pseudomonas most common)
• Gelatinous bile leads to biliary obstruction and fibrosis with secondary biliary cirrhosis
• Infertility due to obstruction of epididymis and vas, intestinal obstruction producing meconium ileus in 5-10% of newborns.

• Abnormal secretory function produces thick viscid material causing flow obstruction, tissue damage, organ atrophy and fibrosis
• Chronic pulmonary disease
• pancreatic insufficiency and malnutrition,
• liver cirrhosis
• male infertility
• intestinal obstruction
• nasal polyps
• other secretory related abnormalities present in disease.

• definition- inflammation and necrosis of the pancreas whose severity may range from mild to life threatening
• Major etiologies
  • cholelithiasis (women > men)
  • alcoholism (men > women)
  • Others conditions such as
    • metabolic abnormalities (hyperlipidemia, hypercalcemia), drugs
    • infection
    • trauma
    • shock
    • ischemia

• duct obstruction, acinar cell injury, or abnormal intracellular transport and fusion of zymogen/lysosomal granules 
• all processes causing pancreatitis begin by intrapancreatic activation of enzymes, probably initiated by activated trypsin
• lead to proteolysis, fat necrosis, hemorrhage, and inflammation
• Activated enzymes cause damage and necrosis to pancreatic tissue, adjacent fat, blood vessels
• producing hemorrhagic destruction of the gland with associated inflammatory reaction.
• release of free FA's
• bind calcium, causing hypocalcemia

• Clinical presentation of “acute abdomen” (must rule out peptic ulcer perforated viscus, mesenteric infarction, etc.), with self-limited course treated by supportive care. 
• dx- supported by:
  • serum/urine enzyme elevation (amylase, lipase)
  • Severity of disease monitored by glucose elevation, increase WBC, rising LDH and SGOT
  • The extent of disease may also be evaluated by CT scan.
• Risk of mortality increases with:
  • decreasing hematocrit
  • rise in BUN and fluid sequestration,
  • fall in Ca+2 and pO2

• complications
  • shock (with multiorgan failure
  • pulmonary insufficiency
  • renal failure
  • metabolic abnormalities
  • obstruction to biliary or duodenal flow. 
  • Pancreatic abscess, pseudocysts with or without infection, and perforation may appear within the first two weeks
• tx
  • supportive care with maintenance of pulmonary, renal, metabolic function. 
  • Surgery is usually not indicated, but may be performed if diagnosis is in doubt to:
    • remove impacted stones causing pancreatitis
    • drainage of pancreatic abscess
    • drainage of pseudocysts that enlarge or persist beyond 2 months.

• proteolytic destruction of the gland with parenchymal necrosis associated with necrosis of blood vessels and hemorrhage
• fat necrosis due to lipase activity
• exudative reaction and neutrophilic inflammation

• chronic alcohol abuse(by far the most importanat)
• chronic mechanical obstruction of the pancreatic duct
• cystic fibrosis
• rarely tropical pancreatitis or hereditary pancreatitis.

• chronic duct obstruction with duct concretions
• toxic-metabolic injury and oxidative stress, usually from alcohol disease
• necrosis-fibrosis cycles in cases of hereditary pancreatitis due to the loss of function of trypsin inactivators or inhibitors.

• fibrous scarring with loss of acini
• duct dilatation with mucus plugs
• chronic inflammatory reaction around lobules and ducts
• residual islets within the fibrous scar. 
• Pseudocysts may also complicate chronic pancreatitis
• fibrosis may also cause common bile duct obstruction

• repeated attacks of pain
• possibly maldigestion
• low albumin with ascites
• jaundice

• epidemiology- male predominance
• clinical presentation
  • non-specific pain
  • jaundice (painless enlarged gallbladder–Courvoisier’s sign)
  • metastases.
  • induces procoagulant state with migratory thrombophlebitis (Trousseau’s sign)
• prognosis- majority of patients die within 1 to 2 years
  • no effective chemo or radiation therapy

• usually exocrine tumors
• tend to grow silently at the head of the pancreas, obstructing the biliary duct, leading to extrahepatic jaundice
• etiology- unclear, but points to chronic pancreatitis (some evidence with smoking, diet)

• arise from precursor lesions, called pancreatic intraepithelial neoplasia (PanIN)
• progressive changes of duct epithelial dysplasia accompanied by a series of mutations involving mutations of:
  • K-ras (oncogene)
  • inactivation of p16 and p53 (tumor suppressor genes)
  • other gene abnormalities

• adenocarcinoma (mucin or non-mucin secreting) with tumor nests
• poorly formed malignant glands invading a desmoplastic (fibrous) stroma
• tumor infiltration of lymphatic and vascular channels
• extension of tumor to peripancreatic tissue
• early metastases to lymph nodes and later to liver. 

• prognosis- the tumor is often in advanced stage at discovery
  • commonly pre-operative radiologic studies show extensive or metastatic disease preventing resection 
• tx
  • Surgery performed if individual is operable and tumor is resectabl
  • Surgery may be performed for palliative drainage if obstruction is present