biliary tract and pancreas
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General PathologyBiliary Tract and Pancreas1 December 07
Biliary Tract
Bile
Two major functions
o Elimination of bilirubin, excess cholesterol, and
xenobiotics that are insufficiently water soluble to be
excreted in urine
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
Bile ductular proliferation
Bile lakes
Portal tract fibrosis
Secondary Biliary Cirrhosis
Most common cause is extrahepatic cholelithiasis
Biliary atresia, malignancies of the biliary tree and head of
the pancreas, and strictures
Cholestasis
Bile duct proliferation with surrounding neutrophils
Periportal fibrosis
Primary Biliary Cirrhosis
Middle-aged women
M:F = 1:10
Possibly autoimmune
o Autoantibodies to mitochondrial pyruvate
dehydrogenase 90% Insidious onset, usually presenting with pruritus
Hyperbilirubinemia, jaundice, cirrhosis late
alkaline phosphatase, cholesterol
Figure 1-Nonsuppurative, granulomatous destruction of medium-sized
intrahepatic bile ducts = florid duct lesion
Primary Sclerosing Cholangitis
Inflammation, obliterative onion-skin fibrosis, and segmental
dilatation of the obstructed intrahepatic and extrahepatic bile
ducts
String of beads on ERCP
70% associated with inflammatory bowel disease,
particularly ulcerative colitis
M:F = 2:1, third through fifth decades
Progressive fatigue, pruritus, jaundice
Chronic course
Increased risk for cholangiocarcinoma
Cholelithiasis
Very common
Cholesterol stones
o Bile is supersaturated with cholesterol
o Gallbladder stasis
o F>Mo Obesity
o Advancing age
Pigment stones calcium bilirubinate salts
o Asian more than Western
o Chronic hemolytic syndromes
Clinical Featureso Asymptomatic
o Biliary colic
o Cholecystitis
o Gallstone ileus
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Cholecystitis
Acute calculous
o Obstruction of GB neck or cystic duct
o RUQ pain radiating to right shoulder
o Fever, nausea, leukocytosis
o Potential surgical emergency
Acute acalculous seriously ill pts
Chronic
o Recurrent attacks of pain
o Nausea and vomiting
o Associated with fatty meals
Choledocholithiasis
Stones within the biliary tree
West from gallbladder
Asia primary ductal and intrahepatic stone formation
Symptoms due to:
o Biliary obstruction
o Pancreatitis
o Cholangitis
o Hepatic abscess
Cholangitis
Acute inflammation of bile ducts
Due to biliary obstruction, usually choledocholithiasis
Bacterial infection from gut, i.e., gram negative aerobes
o Fever, chills, abdominal pain, jaundice
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
Complete obstruction of bile flow caused by destruction o
absence of all or part of the extrahepatic bile ducts
Acquired inflammatory disorder
Normal stools to acholic stools
Bile ductular proliferation on liver bx
Cirrhosis by 3 to 6 months of age.
Require liver transplantation
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%
Cholangiocarcinoma
Older pts
M>F
Painless jaundice, N/V, weight loss
Opisthorchis sinensis (liver fluke),inflammatory bowe
disease
Tumors usually small at dx yet not resectable Klatskin tumor arises at bifurcation
Adenocarcinoma
Mean survival 6 to 18 months
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Pancreas
Brief History
Herophilus, Greek surgeon first described pancreas.
Wirsung discovered the pancreatic duct in 1642.
Pancreas as a secretory gland was investigated by Graaf in
1671.
R. Fitz established pancreatitis as a disease in 1889.
Whipple performed the first pancreatico-duodenectomy in
1935 and refined it in 1940.
Pancreas
Gland with both exocrine and endocrine functions
6-10 inch in length
60-100 gram in weight
Location: retro-peritoneum*, 2nd lumbar vertebral level Extends in an oblique, transverse position
Parts of pancreas: head, neck, body and tail
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)
Head of Pancreas
Includes uncinate process
Flattened structure, 2 3 cm thick
Attached to the 2nd and 3rd portions of duodenum on the
right
Emerges into neck on the left
Border b/w head & neck is determined by GDA insertion
SPDA and IPDA anastamose b/w the duodenum and the rt
lateral border
Neck of Pancreas
2.5 cm in length
Straddles SMV and PV
Antero-superior surface supports the pylorus
Superior mesenteric vessels emerge from the inferior border
Posteriorly, SMV and splenic vein confluence to form porta
vein
Posteriorly, mostly no branches to pancreas
Body of Pancreas
Elongated, long structure
Anterior surface, separated from stomach by lesser sac
Posterior surface, related to aorta, lt. adrenal gland, lt. rena
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 12 th thoracic vertebra
Ends within the splenic hilum
Lies in the splenophrenic ligament
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Anteriorly, related to splenic flexure of colon
May be injured during splenectomy (fistula)
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) thuspreventing damage to panc. duct
Lesser duct (Santorini) drains superior portion of head and
empties separately into 2nd portion of duodenum
Arterial Supply of the Pancreas
Variety of major arterial sources (celiac, SMA and splenic)
Celiac Common Hepatic Artery Gastroduodenal Artery
Superior pancreaticoduodenal artery which divides into
anterior and posterior branches
SMA Inferior pancreaticoduodenal artery which divides
into anterior and posterior branches
Anterior collateral arcade b/w anterosuperior and
anteroinferior PDA
Posterior collateral arcade b/w posterosuperior and
posteroinferior PDA
Body and tail supplied by splenic artery by about 10
branches
Three biggest branches are
o Dorsal pancreatic artery
o Pancreatica Magna (midportion of body)
o Caudal pancreatic artery (tail)
Venous Drainage of Pancreas
Follows arterial supply
Anterior and posterior arcades drain head and the body
Splenic vein drains the body and tail
Major drainage areas are
o Suprapancreatic PV
o Retropancreatic PV
o Splenic vein
o Infrapancreatic SMV
Ultimately, into portal vein
Lymphatic Drainage
Rich periacinar network that drain into 5 nodal groups
o Superior nodes
o Anterior nodes
o Inferior nodes
o Posterior PD nodes
o Splenic nodes
Innervation of Pancreas
Peptidergic neurons that secrete amines and peptides(somatostatin, vasoactive intestinal peptide, calcitonin gene
related peptide, and galanin
Rich afferent sensory fiber network
Ganglionectomy or celiac ganglion blockade interrupt these
somatic fibers (pancreatic pain*)
Peptidergic neurons that secrete amines and peptides
(somatostatin, vasoactive intestinal peptide, calcitonin gene
related peptide, and galanin
Rich afferent sensory fiber network
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
Acinus small intercalated ducts interlobular duct
pancreatic duct
Interlobular ducts contribute to fluid and electrolyte secretion
along with the centroacinar cells
Histology-Endocrine Pancreas
Accounts for only 2% of the
pancreatic mass
Nests of cells - islets of
Langerhans
Four major cell types
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o Alpha (A) cells secrete glucagon
o Beta (B) cells secrete insulin
o Delta (D) cells secrete somatostatin
o F cells secrete pancreatic polypeptide
B cells are centrally located within the islet and constitute
70% of the islet mass
PP, A, and D cells are located at the periphery of the islet
Physiology Exocrine Pancreas
Secretion of water and electrolytes originates in the
centroacinar and intercalated duct cells
Pancreatic enzymes originate in the acinar cells
Final product is a colorless, odorless, and isosmotic alkaline
fluid that contains digestive enzymes (amylase, lipase, and
trypsinogen)
500 to 800 ml pancreatic fluid secreted per day
Alkaline pH results from secreted bicarbonate which serves
to neutralize gastric acid and regulate the pH of the intestine
Enzymes digest carbohydrates, proteins, and fats
Bicarbonate Secretion
Bicarbonate is formed from carbonic acid by the enzyme
carbonic anhydrase
Major stimulants
Secretin, Cholecystokinin, Gastrin, Acetylcholine
Major inhibitors
Atropine, Somatostatin, Pancreatic polypeptide and
Glucagon
Secretin - released from the duodenal mucosa in response
to a duodenal luminal pH < 3
Enzyme Secretion
Acinar cells secrete isozymes
o amylases, lipases, and proteases
Major stimulants
o Cholecystokinin, Acetylcholine, Secretin, VIP
Synthesized in the endoplasmic reticulum of the acinar cells
and are packaged in the zymogen granules
Released from the acinar cells into the lumen of the acinus
and then transported into the duodenal lumen, where the
enzymes are activated.
Enzymes of the Pancreas
Amylase
o only digestive enzyme secreted by the
pancreas in an active form
o functions optimally at a pH of 7
o hydrolyzes starch and glycogen to glucose,
maltose, maltotriose, and dextrins
Lipase
o function optimally at a pH of 7 to 9
o emulsify and hydrolyze fat in the presence of bile salts
Proteases
o essential for protein digestion
o secreted as proenzymes and require activation fo
proteolytic activity
o duodenal enzyme, enterokinase, converts trypsinogen
to trypsin
o Trypsin, in turn, activates chymotrypsin, elastase
carboxypeptidase, and phospholipase
Within the pancreas, enzyme activation is prevented by an
antiproteolytic enzyme secreted by the acinar cells
Insulin
Synthesized in the B cells of the islets of Langerhans
80% of the islet cell mass must be surgically removed
before diabetes becomes clinically apparent
Proinsulin, is transported from the endoplasmic reticulum to
the Golgi complex where it is packaged into granules and
cleaved into insulin and a residual connecting peptide, or C
peptide
Major stimulants
o Glucose, amino acids, glucagon, GIP, CCK
sulfonylurea compounds, -Sympathetic fibers
Major inhibitors
o somatostatin, amylin, pancreastatin, -sympathetic
fibers
Glucagon
Secreted by the A cells of the islet
Glucagon elevates blood glucose levels through the
stimulation of glycogenolysis and gluconeogenesis
Major stimulants
o Aminoacids, Cholinergic fibers, -Sympathetic fibers
Major inhibitors
o Glucose, insulin, somatostatin, -sympathetic fibers
Somatostatin
Secreted by the D cells of the islet
Inhibits the release of growth hormone
Inhibits the release of almost all peptide hormones
Inhibits gastric, pancreatic, and biliary secretion
Used to treat both endocrine and exocrine disorders
Exocrine Pancreas
The final product of the exocrine pancreas is a clear isotonic
solution with a pH in the range of 8. The 2 distinc
components of exocrine secretion are enzyme secretion andwater+electrolyte secretion.
Cholecystokinin is the most potent endogenous hormone
known to stimulate enzyme secretion.
Secretin is the most potent endogenous stimulant o
pancreatic electrolyte secretion.
Endocrine Pancreas
The release of insulin into the portal blood is controlled by
the concentration of blood glucose, vagal interactions, and
local concentrations of somatostatin.
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The major stimulus for glucagon release is a fall in serum
glucose.
Pancreatic polypeptide appears to function for regulation of
pancreatic exocrine secretion and biliary tract motility.
Somatostatin has a broad inhibitory spectrum of
gastrointestinal activity
Congenital anomalies Agenesis
Pancreas divisum
Annular pancreas
Ectopic pancreas
Acute Pancreatitis
Nonbacterial inflammatory disease caused by activation,
interstitial liberation, and autodigestion of the pancreas by
its own enzymes.
Inconclusive evidence regarding pathogenesis
o Partial or intermittent ductal obstruction and increased
ductal pressureo Biliary reflux
o Duodenal juice reflux
Etiology
o Gallstones and Alcohol account for 90%
o Hyperlipidemia
o Hypercalcemia
o Familial
o Pancreatic duct obstruction
Tumour
Pancreas divisum
o Viral infectiono Scorpion venom
o Drugs
o Idiopathic
Signs and Symptoms
o Midepigastric abdominal pain
o Radiating to the back
o Nausea and vomiting
o Fever and tachycardia
o Epigastric tenderness
o Abdominal distention
o Bluish discoloration in the flank (Grey Turners sign)
o Bluish discoloration periumbilically (Cullens sign)
Diagnosis
o It is supported by appropriate laboratory determinations
and radiographic findings
o Serum amylase is the most widely used lab test
o Hyperamylasemia is commonly observed within 24 hrs.
of the onset and gradually returns to normal
o Persistent hyperamylasemia beyond the initial week
may indicate the development of pancreatic
pseudocyst, phlegmon, abscess or ongoing acute
pancreatic inflammation.
o Elevated amylase levels may occur in other acute
abdominal conditions, though levels rarely exceed 500
IU/dL
o Urinary amylase excretion is increased and this may be
very helpful in cases where the serum amylase leve
has returned to normal.
o Other lab. Findings
Moderate leukocytosis
Mild bilirubin elevation (55 years
WBC >16000
Blood Glucose >200 mg/dL
LDH >350 iu/L
AST (SGOT) > 250 iu/dL
o After 24 hours
Hematocrit fall >10%
BUN rise >8mg/dL
Serum Ca 600 mL
o Predicted Mortality Rates
0-2 criteria = 2%
3 or 4 criteria = 15%
5 or 6 criteria = 40%
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7 or 8 criteria = 100%
Glasgow prognostic system
Treatment
Goals of medical treatment
o Reduction of pancreatic secretory stimuli
o Correction of fluid and electrolyte derangements
Complications
o Abscess
o Pseudocyst formation
o Pancreatic ascites
o Chronic pleural effusion
o Gastrointestinal bleeding
o Acute splenic vein thrombosis
o Chronic Pancreatitis
Pancreatic Pseudocyst
The term pseudocyst denotes absence of an epithelial lining
in contrast to true cysts
Encapsulated collections of fluid with high enzyme
concentrations that arise from the pancreas.
They are usually located either within or adjacent to the
pancreas in the lesser sac.
The walls of a pseudocyst are formed by inflammatory
fibrosis of the peritoneal, mesenteric and serosalmembranes which limits spread of the pancreatic juice as
the lesion develops.
Early or late presentation
Pain is the most common finding
Fever, weight loss, tenderness, palpable mass
Jaundice rarely
Elevated amylase and WBC in ~ 50%
CT scan is the investigation of choice
D/D Abscess, phlegmon, neoplastic cysts
Complications
o Infection Abscess
o Rupture Severe chemical peritonitis
o Haemorrhage
Chronic Pancreatitis
Is an entity encompassing recurrent or persistent abdomina
pain of pancreatic origin combined with evidence of exocrine
and endocrine insufficiency and marked pathologically byirreversible parenchymal destruction.
It is associated with alcohol abuse, Hyperparathyroidism
congenital anomalies of the pancreatic duct and pancreatic
trauma. It may also be idiopathic.
Neoplasms of the Pancreas
Exocrine Tumours
A. Periampullary Carcinoma
Cancer of the head of pancreas 85%
Ampullary carcinoma 10%
Duodenal carcinomas
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Resectability rate
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o Oncocytic CA
o Clear cell CA
o Signet ring
o Mucinous CA
Most common Sites of Metz
o peritoneum
o Lung
o
Adrenalo Bone
o Distal lymph nodes
o skin
o CNS
Cytology
o Duodenal secretion
o Pancreatic Juice
o Percutaneous FNA
o Intraop FNA
Treatment: Surgical
o Body & tail distal pancreatectomy
o Head Whipple operation + retroperitoneal resectiono Paliative bypass operation
Giant Cell Tumor
large & hemorrhagic
Dual population:
o Spindle cells
o Multinucleated giant cells
Some cases, clear cut glandular appearance
Microcystic Cystadenoma
A.k.a.glycogen-rick cystadenoma
Large multinucleated mass, small cysts filled with clear
serous fluid
Microscopic: small flat to cuboidal lining
Layer of myoepithelium
IHC: EMA, LMW keratin
Elderly
Microcystic Adenocarcinoma
Similar to microcystic adenoma but with nuclear atypia,
pleomorphism, metastasis
Mucinous Cystic Neoplasm
Younger age group
Women
Large multiloculated or unilocular lined by tall mucin
producing cells
High levels of CEA
Mucinous Cyst Adenoma vs. Mucinous CystadenoCA
distinction not always clear cut
Intraductal Neoplasm
Intraductal Papillary Carcinomao Involve major ducts, multicentric
Mucus secreting or Mucin Producing Duct-Ectatic Tumor
o Dilated ducts filled with mucus
o Columnar, mucin producing, well diff
o Overexpression or c-erb-2
Acinar Cell Tumor & Tumor-like Conditions
Acinar Cell Hyperplasia
Acinar Cell Adenoma
Acinar Cell Carcinoma
Acinic Cell Carcinoma
IHC
o Trypsin
o Lipase
o Chymotrypsin
o amylase
Abundant ER on EM
Metastasis present in the time of diagnosis
Papillary & Solid Epithelial Neoplasm
Young women
Large with areas of necrosis and hemorrhage, some with
well developed capsule
Microscopic: very cellular, simulates islet cell tumor
o Pseudopapillae covered by layers of epithelial cells
o Nuclei are ovoid and folded
o Distict nucleoli, few mitoses
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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
Haay, ang haba
Feeling ko tlga ndi na kmi trans nito e.
Oist, new year na! Magbagong buhay na kau! :-p