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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General Pathology Biliary Tract and Pancreas byVGY Page 2 of 10

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%



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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

Biliary Tract and Pancreas

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