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Biliary Tract and Pancreas
Biliary Tract and Pancreas
Biliary Tract and Pancreas
andPathology
with inflammatory
Tract bowel disease,
Pancreas
Bile particularly1ulcerative
December 07
colitis
• Two major functions • M:F = 2:1, third through fifth decades
o Elimination of bilirubin, excess cholesterol, and • Progressive fatigue, pruritus, jaundice
xenobiotics that are insufficiently water soluble to be • Chronic course
excreted in urine • Increased risk for cholangiocarcinoma
o Emulsification of dietary fat in the gut by bile acids
(cholic acid, chenodeoxycholic acid)
• Unconjugated → Conjugated
• Reabsorbed in terminal ileum (enterohepatic circulation)
Cholestasis
• Systemic retention of not only bilirubin but also other solutes
eliminated in bile, particularly bile salts and cholesterol
• Due to hepatocellular dysfunction or biliary obstruction
• Accumulation of bile pigment within the hepatic parenchyma
– Kupffer cells
Cholelithiasis
• Bile ductular proliferation
• Very common
• Bile lakes
• Cholesterol stones
• Portal tract fibrosis
o Bile is supersaturated with cholesterol
o Gallbladder stasis
Secondary Biliary Cirrhosis
o F>M
• Most common cause is extrahepatic cholelithiasis
• Biliary atresia, malignancies of the biliary tree and head of o Obesity
the pancreas, and strictures o Advancing age
• Cholestasis • Pigment stones – calcium bilirubinate salts
• Bile duct proliferation with surrounding neutrophils o Asian more than Western
• Periportal fibrosis o Chronic hemolytic syndromes
• Clinical Features
Primary Biliary Cirrhosis o Asymptomatic
• Middle-aged women o Biliary colic
• M:F = 1:10 o Cholecystitis
• Possibly autoimmune
o Gallstone ileus
o Autoantibodies to mitochondrial pyruvate
dehydrogenase 90%
• Insidious onset, usually presenting with pruritus
• Hyperbilirubinemia, jaundice, cirrhosis late
• ↑ alkaline phosphatase, cholesterol
Gallbladder Carcinoma
• Seventh decade
• F>M
• Discovered at late stage, usually incidental
• Exophytic and infiltrating types
• Adenocarcinoma
• Local extension into liver, cystic duct, portahepatic LNs
• Mean 5 yr survival 1%
Choledocholithiasis
• Stones within the biliary tree
• West – from gallbladder
• Asia – primary ductal and intrahepatic stone formation
• Symptoms due to:
o Biliary obstruction
o Pancreatitis Cholangiocarcinoma
o Cholangitis • Older pts
• M>F
o Hepatic abscess
• Painless jaundice, N/V, weight loss
• Opisthorchis sinensis (liver fluke),inflammatory bowel
Cholangitis
disease
• Acute inflammation of bile ducts
• Tumors usually small at dx yet not resectable
• Due to biliary obstruction, usually choledocholithiasis
• Klatskin tumor – arises at bifurcation
• Bacterial infection from gut, i.e., gram negative aerobes
• Adenocarcinoma
o Fever, chills, abdominal pain, jaundice
• Mean survival 6 to 18 months
• Latin America and Near East: Fasciola hepatica,
schistosomiasis
• Far East: Clonorchis sinensis, Opisthorchis viverrini
• AIDS: cryptosporidiosis
Biliary Atresia
• 1/3 of cases of neonatal cholestasis
• 1 in 10,000 live births
General Pathology – Biliary Tract and Pancreas by VGY Page 3 of 10
Head of Pancreas
• Includes uncinate process
• Flattened structure, 2 – 3 cm thick
Pancreas
Brief History • Attached to the 2nd and 3rd portions of duodenum on the
• Herophilus, Greek surgeon first described pancreas. right
• Wirsung discovered the pancreatic duct in 1642. • Emerges into neck on the left
• Pancreas as a secretory gland was investigated by Graaf in • Border b/w head & neck is determined by GDA insertion
1671. • SPDA and IPDA anastamose b/w the duodenum and the rt.
• R. Fitz established pancreatitis as a disease in 1889. lateral border
• Whipple performed the first pancreatico-duodenectomy in
1935 and refined it in 1940. Neck of Pancreas
• 2.5 cm in length
Pancreas
• Straddles SMV and PV
• Gland with both exocrine and endocrine functions
• Antero-superior surface supports the pylorus
• 6-10 inch in length
• 60-100 gram in weight • Superior mesenteric vessels emerge from the inferior border
• Location: retro-peritoneum*, 2nd lumbar vertebral level • Posteriorly, SMV and splenic vein confluence to form portal
• Extends in an oblique, transverse position vein
• Parts of pancreas: head, neck, body and tail • Posteriorly, mostly no branches to pancreas
Embryology
• Endodermal origin
• Develops from ventral and dorsal pancreatic buds
• Ventral bud becomes the uncinate process and inferior head
of pancreas
• Dorsal bud becomes superior head, neck, body and tail
• Ventral bud duct fuses with dorsal bud duct to become mail
pancreatic duct (Wirsung)
Body of Pancreas
• Elongated, long structure
• Anterior surface, separated from stomach by lesser sac
• Posterior surface, related to aorta, lt. adrenal gland, lt. renal
vessels and upper 1/3rd of lt. kidney
• Splenic vein runs embedded in the post. Surface
• Inferior surface is covered by tran. mesocolon
Tail of Pancreas
• Narrow, short segment
• Lies at the level of the 12th thoracic vertebra
• Ends within the splenic hilum
• Lies in the splenophrenic ligament
General Pathology – Biliary Tract and Pancreas by VGY Page 4 of 10
Pancreatic Duct
• Main duct (Wirsung) runs the entire length of pancreas
• Joins CBD at the ampulla of Vater
• 2 – 4 mm in diameter, 20 secondary branches
• Ductal pressure is 15 – 30 mm Hg (vs. 7 – 17 in CBD) thus
preventing damage to panc. duct
• Lesser duct (Santorini) drains superior portion of head and
empties separately into 2nd portion of duodenum Lymphatic Drainage
• Rich periacinar network that drain into 5 nodal groups
Arterial Supply of the Pancreas o Superior nodes
• Variety of major arterial sources (celiac, SMA and splenic) o Anterior nodes
• Celiac à Common Hepatic Artery à Gastroduodenal Artery o Inferior nodes
à Superior pancreaticoduodenal artery which divides into o Posterior PD nodes
anterior and posterior branches o Splenic nodes
• SMA à Inferior pancreaticoduodenal artery which divides
into anterior and posterior branches Innervation of Pancreas
• Anterior collateral arcade b/w anterosuperior and • Peptidergic neurons that secrete amines and peptides
anteroinferior PDA (somatostatin, vasoactive intestinal peptide, calcitonin gene-
• Posterior collateral arcade b/w posterosuperior and related peptide, and galanin
posteroinferior PDA • Rich afferent sensory fiber network
• Body and tail supplied by splenic artery by about 10 • Ganglionectomy or celiac ganglion blockade interrupt these
branches somatic fibers (pancreatic pain*)
• Three biggest branches are • Peptidergic neurons that secrete amines and peptides
o Dorsal pancreatic artery (somatostatin, vasoactive intestinal peptide, calcitonin gene-
related peptide, and galanin
o Pancreatica Magna (midportion of body)
• Rich afferent sensory fiber network
o Caudal pancreatic artery (tail)
• Ganglionectomy or celiac ganglion blockade interrupt these
somatic fibers (pancreatic pain*)
Histology-Exocrine Pancreas
• 2 major components – acinar cells and ducts
• Constitute 80% to 90% of the pancreatic mass
• Acinar cells secrete the digestive enzymes
• 20 to 40 acinar cells coalesce into a unit called the acinus
• Centroacinar cell (2nd cell type in the acinus) is responsible
for fluid and electrolyte secretion by the pancreas
• Ductular system - network of conduits that carry the
exocrine secretions into the duodenum
Venous Drainage of Pancreas
• Follows arterial supply • Acinus à small intercalated ducts à interlobular duct à
• Anterior and posterior arcades drain head and the body pancreatic duct
• Interlobular ducts contribute to fluid and electrolyte secretion
• Splenic vein drains the body and tail
along with the centroacinar cells
• Major drainage areas are
o Suprapancreatic PV
Histology-Endocrine Pancreas
o Retropancreatic PV
• Accounts for only 2% of the
o Splenic vein
pancreatic mass
o Infrapancreatic SMV • Nests of cells - islets of
• Ultimately, into portal vein Langerhans
• Four major cell types
General Pathology – Biliary Tract and Pancreas by VGY Page 5 of 10
o Alpha (A) cells secrete glucagon o secreted as proenzymes and require activation for
o Beta (B) cells secrete insulin proteolytic activity
o Delta (D) cells secrete somatostatin o duodenal enzyme, enterokinase, converts trypsinogen
o F cells secrete pancreatic polypeptide to trypsin
• B cells are centrally located within the islet and constitute o Trypsin, in turn, activates chymotrypsin, elastase,
70% of the islet mass carboxypeptidase, and phospholipase
• PP, A, and D cells are located at the periphery of the islet • Within the pancreas, enzyme activation is prevented by an
antiproteolytic enzyme secreted by the acinar cells
Physiology – Exocrine Pancreas
• Secretion of water and electrolytes originates in the Insulin
centroacinar and intercalated duct cells • Synthesized in the B cells of the islets of Langerhans
• Pancreatic enzymes originate in the acinar cells • 80% of the islet cell mass must be surgically removed
before diabetes becomes clinically apparent
• Final product is a colorless, odorless, and isosmotic alkaline
• Proinsulin, is transported from the endoplasmic reticulum to
fluid that contains digestive enzymes (amylase, lipase, and
the Golgi complex where it is packaged into granules and
trypsinogen)
cleaved into insulin and a residual connecting peptide, or C
• 500 to 800 ml pancreatic fluid secreted per day
peptide
• Alkaline pH results from secreted bicarbonate which serves
• Major stimulants
to neutralize gastric acid and regulate the pH of the intestine
o Glucose, amino acids, glucagon, GIP, CCK,
• Enzymes digest carbohydrates, proteins, and fats
sulfonylurea compounds, β-Sympathetic fibers
• Major inhibitors
Bicarbonate Secretion
• Bicarbonate is formed from carbonic acid by the enzyme
o somatostatin, amylin, pancreastatin, α-sympathetic
carbonic anhydrase fibers
• Major stimulants
Glucagon
Secretin, Cholecystokinin, Gastrin, Acetylcholine
• Secreted by the A cells of the islet
• Major inhibitors
• Glucagon elevates blood glucose levels through the
Atropine, Somatostatin, Pancreatic polypeptide and
Glucagon stimulation of glycogenolysis and gluconeogenesis
• Secretin - released from the duodenal mucosa in response • Major stimulants
to a duodenal luminal pH < 3 o Aminoacids, Cholinergic fibers, β-Sympathetic fibers
• Major inhibitors
Enzyme Secretion o Glucose, insulin, somatostatin, α-sympathetic fibers
• Acinar cells secrete isozymes
o amylases, lipases, and proteases Somatostatin
• Secreted by the D cells of the islet
• Major stimulants • Inhibits the release of growth hormone
o Cholecystokinin, Acetylcholine, Secretin, VIP
• Inhibits the release of almost all peptide hormones
• Synthesized in the endoplasmic reticulum of the acinar cells
• Inhibits gastric, pancreatic, and biliary secretion
and are packaged in the zymogen granules
• Released from the acinar cells into the lumen of the acinus • Used to treat both endocrine and exocrine disorders
and then transported into the duodenal lumen, where the
enzymes are activated. Exocrine Pancreas
• The final product of the exocrine pancreas is a clear isotonic
Enzymes of the Pancreas solution with a pH in the range of 8. The 2 distinct
• Amylase components of exocrine secretion are enzyme secretion and
o only digestive enzyme secreted by the water+electrolyte secretion.
pancreas in an active form • Cholecystokinin is the most potent endogenous hormone
o functions optimally at a pH of 7 known to stimulate enzyme secretion.
o hydrolyzes starch and glycogen to glucose, • Secretin is the most potent endogenous stimulant of
maltose, maltotriose, and dextrins pancreatic electrolyte secretion.
• Lipase
Endocrine Pancreas
o function optimally at a pH of 7 to 9
o emulsify and hydrolyze fat in the presence of bile salts • The release of insulin into the portal blood is controlled by
• Proteases the concentration of blood glucose, vagal interactions, and
o essential for protein digestion local concentrations of somatostatin.
General Pathology – Biliary Tract and Pancreas by VGY Page 6 of 10
• The major stimulus for glucagon release is a fall in serum pseudocyst, phlegmon, abscess or ongoing acute
glucose. pancreatic inflammation.
o Elevated amylase levels may occur in other acute
• Pancreatic polypeptide appears to function for regulation of
abdominal conditions, though levels rarely exceed 500
pancreatic exocrine secretion and biliary tract motility.
IU/dL
• Somatostatin has a broad inhibitory spectrum of o Urinary amylase excretion is increased and this may be
gastrointestinal activity very helpful in cases where the serum amylase level
has returned to normal.
Congenital anomalies o Other lab. Findings
• Agenesis Moderate leukocytosis
• Pancreas divisum Mild bilirubin elevation (<2mg/dL)
• Annular pancreas Raised Haematocrit
• Ectopic pancreas Hypocalcaemia (Calcium being complexed with
fatty acids)
Acute Pancreatitis
• Nonbacterial inflammatory disease caused by activation, • Radiographic Findings
interstitial liberation, and autodigestion of the pancreas by o CXR and PFA non-specific findings
its own enzymes. Sentinel loop
• Inconclusive evidence regarding pathogenesis Pleural effusion (Left)
o Partial or intermittent ductal obstruction and increased o Abdominal Ultrasonography
ductal pressure Lithiasis of biliary tract
o Biliary reflux Pancreatic swelling
o Duodenal juice reflux o Computed Tomography with iv contrast
Chronic Pancreatitis
• Is an entity encompassing recurrent or persistent abdominal
pain of pancreatic origin combined with evidence of exocrine
and endocrine insufficiency and marked pathologically by
irreversible parenchymal destruction.
• It is associated with alcohol abuse, Hyperparathyroidism,
congenital anomalies of the pancreatic duct and pancreatic
trauma. It may also be idiopathic.
Microcystic Cystadenoma
• A.k.a.glycogen-rick cystadenoma
• Large multinucleated mass, small cysts filled with clear Acinic Cell Carcinoma
serous fluid • IHC
• Microscopic: small flat to cuboidal lining o Trypsin
Layer of myoepithelium o Lipase
• IHC: EMA, LMW keratin o Chymotrypsin
• Elderly o amylase
• Abundant ER on EM
• Metastasis present in the time of diagnosis
o Hyaline globules
o Thick fibrovascular core with mucinous change
• Ultrastructure
o Acinar, ductal, & endocrine differentiation
• IHC
o Keratin, desmoplakin, trypsin, chymotrypsin, amylase &
vimentin
o Focal reactivity: NSE, islet cell hormones