exocrine pancreas

THE PANCREAS

.

Anatomy

Pancreas – “all flesh” Transversely oriented retroperitoneal

organ Extending from “C”loop of duodenum to

the hilum of spleen Measures 20 cm in length Weighs 90gms in men,85gms in women.

3 parts

Head Body Tail

Pancreatic duct system

Highly variable. Main pancreatic duct –duct of Wirsung-

papilla of Vater. Accessory pancreatic duct –duct of

Santorini- minor papilla MPD merges with CBD to form ampulla of

Vater.

Embryology

From fusion of dorsal & ventral outpouchings of foregut.

Dorsal primordium- body,tail superior aspect of head & accessory duct.

Ventral primordium- inferior part of head, major duct.

Functional Anatomy

Complex lobulated organ Distinct exocrine & endocrine components Exocrine -80 to 85% of pancreas. Endocrine- 1 to 2% Exocrine-acinar cells & a series of ductules &

ducts Endocrine- about 1million clusters of cells- islets

of Langerhans

Histology

Acinar cells- pyramidally shaped epithelial cells radially oriented around a central lumen.

Basal portion-deeply basophilic-abundant ER. Supranuclear golgi complex Membrane bound zymogen granules-granular

eosinophilic appearance to the apices. Smaller ductules-lined by cuboidal cells-secrete fluid rich

in bicarbonate. Larger ducts-columnar cells –mucin-express cystic

fibrosis trans membrane conductance regulator

Physiology

Secretes 2 to 2.5 liters of bicarbonate rich fluid-digestive enzymes & proenzymes

Neural stimulation- vagus nerve Humoral factors-secretin &

cholecystokinin. Secretin-water & bicarbonate Cholecystokinin-digestive proenzymes

Proenzymes

Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase Kallikreinogen Prophospholipase A & B

Enteropeptidase –cleaves trypsinogen to trypsin

Active enzymes

Amylase Lipase

Prevention of self digestion

Inactive proenzymes Sequestered in zymogen granules Activation requires duodenal enteropeptidase Trypsin inhibitors –SPINK 1- present in acinar cells Trypsin –critical self recognition site-allows trypsin to

inactivate itseif. Lysosomal hydrolases-degrade zymogen granules when

secretion is blocked Acinar cells –resistant to trypsin, chymotrypsin &

phospholipase A 20.

Pathology –exocrine pancreas

Congenital anomalies Acute pancreatitis Chronic pancreatitis Neoplasms

Congenital anomalies

Agenesis very rareassociated with severe malformations incompatible with lifeGermline mutations in homeodomain

transcription factor –IPF 1 gene on chromosome 13q 12.1

Pancreas divisum

Most common clinically significant anomaly. Incidence- 3 to 10% Failure of fusion of fetal duct system of dorsal &

ventral primordia. Bulk of the pancreas -dorsal duct & diminuitive

minor papilla. Main duct is very short Relative stenosis- predisposes to chronic

pancreatitis

Annular pancreas

Relatively uncommon condition Associated with other anomalies Band like ring of normal pancreatic tissue

completely encircling 2nd portion of duodenum May present early in life or in adults Signs & symptoms of duodenal obstruction.

Pancreas

Ectopic pancreas

Present in 2% of careful routine autopsies Favoured sites- stomach,duodenum jejunum,Meckel

diverticula & ileum. Few mms to cms in size & situated in the submucosa. Composed of normal appearing pancreatic acini &

glands ; occasionally islet cells. Usually incidental

sessile masscause pain from local inflammationmay incite mucosal bleedingislet cell tumor -2%

Acute pancreatitis

A group of reversible lesions Characterised by inflammation of the

pancreas. Ranging in severity from edema & fat

necrosis to parenchymal necrosis with severe hemorrhage.

Acute pancreatitis

Relatively common Incidence – 10 to 20 cases per 100,000

people annually. 80% cases are associated with either

biliary tract disease or alcoholism. M :F is 1:3 in biliary tract diseases & 6:1 in

alcoholism.

Etiologic factors

Metabolic

alcoholismhyperlipoprotinemiahypercalcemiadrugsgenetic

Mechanical

traumagall stonesperiampullary tumors,pancreas divisum,choledochoceles,parasites – Ascaris lumbricoides,Clonorchis sinensisiatrogenic injury-perioperative injury,endoscopic procedures(ERCP)

Etiologic factors

VascularshockathroembolismPAN,SLE,HSP

InfectiousMumpsCoxsackieMycoplasma pneumoniae

Drugs

Thiazide diuretics Azathioprine Estrogens Sulphonamides Furosemide Methyl dopa Pentamidine procainamide

Idiopathic

10 to 20% Genetic basis

Hereditary pancreatitis

Autosomal dominant Recurrent attacks of severe pancreatitis beginning in

childhood Caused by germline mutations in the cationic trypsin

gene-PRSS 1 Affects a site on the cationic trypsinogen molecule

essential for the inactivation of trypsin by trypsin itself. Trypsinogen & trypsin become resistant to inactivation

&abnormally active trypsin activates other digestive proenzymes –development of pancreatitis

Hereditory pancreatitis

Inherited homozygous inactivating mutations in the SPINK1 gene(serine protease inhibior,Kazal type1)

SPINK1 gene codes for a pancreatic secretory trypsin inhibitor which helps to prevent autodigestion of pancreas by activated trypsin.

Pathogenesis

Auto digestion of pancreatic tissue by inappropriately activated pancreatic enzymes.

Activation of trypsin is an important triggering event.

3 possible pathways

Pancreatic duct obstruction

Cholelithiasis,ampullary obstructionAccumulation of enzyme rich interstitial fluidLipase-local fat necrosisInjured tissues – proinflammatory cytokines-

IL-1B,IL-6, TNF, PAF, Sub-PLocal inflammtion & interstitial edema-

ischemic injury to acinar cells

Primary acinar cell injury

Viruses,drugs,alcohol,direct trauma Shock Release of intracellular proenzymes

&lysosomal hydrolases Activation of enzymes-acinar cell injury.

Defective intracellular transport

Metabolic injury,alcohol, duct obstruction Delivery of proenzymes to lysosomal

compartment Intracellular activation of enzymes Acinar cell injury

Activated enzymes

Lipase,phospholipase – fat necrosis Proteases – proteolysis Elastase - hemorrhage

Alcohol

Direct toxic effect on acinar cells Duct obstruction – protein rich secretion Sudden exacerbations of chronic

pancreatitis

Morphology

Basic alterations – microvascular leakage – edemafat necrosisacute inflammatory reactionproteolytic destruction of parenchymadestruction of blood vessels – interstitial hemorrhage

Acute interstitial pancreatitis

Mild form Interstitial edema,focal areas of fat

necrosis Released fatty acids + calcium – insoluble

salts

Acute necrotising pancreatitis

More severe form Necrosis of pancreatic tissue, hemorrhage Areas of red-black hemorrhage interspersed with

foci of yellow-white,chalky fat necrosis Foci of fat necrosis in extrapancreatic fat depots Peritoneal cavity – serous ,slightly turbid brown

tinged fluid with fat globules

Hemorrhagic pancreatitis

Most severe form Extensive parenchymal necrosis Diffuse hemorrhage

Clinical features

Abdominal pain – mild to severe Full blown Acute pancreatitis – medical

emergency – “acute abdomen” – constant & intense pain.

Systemic features – release of toxic enzymes,cytokines etc.

Lab findings

Marked elevation of s.amylase during 24hrs

Followed within 72 to 96 hours by a rising s.lipase level.

Hypocalcemia – if persistent –poor prognostic sign.

Diagnosis

Elevated s.amylase & lipase Direct visualisation of the enlarged

inflammed panceas by radiographic means

Exclusion of other causes of acute abdomen.

Complications

Systemic organ failure Shock ARDS ARF DIC Pancreatic abscess P.pseudocyst Duodenal obstruction

Management

“resting” the pancreas Supportive therapy

Chronic pancreatitis

Inflammation Destruction of exocrine parenchyma Fibrosis Destruction of endocrine parenchyma –

late stages.

Chronic vs acute pancreatitis

Irreversible impairment of pancreatic function

Causes

Long term alcohol abuse Long standing obstruction of pancreatic duct by

calculipseudocyststraumaneoplasmspancreas divisum

Tropical pancreatitis

Causes

Hereditary pancreatitis Idiopathic chronic pancreatitis – CFTR

related 40%-no cause.

Pathogenesis

Ductal obstruction by concretions-alcoholic pancreatitis

Toxic-metabolictoxins,alcohol – direct toxic effect on acinar cells

Oxidative stress – alcohol Necrosis – fibrosis in hereditary pancreatitis

repeated attacks of acute pancreatitis – perilobular fibrosis,duct distortion &altered secretions – loss of parenchyma & fibrosis

Chemokines IL-8 MCP-1 TGF-b PDGF

Morphology

Parenchymal fibrosis Reduced no & size of acini ,relative sparing of islets Variable dilatation of the ducts Chronic inflammatory infiltrate around lobules & ducts Interlobular & intralobular ducts – dilated,contain protein

plugs Ductal epithelium – atrophied or hyperplastic Ductal concretions

Morphology

Acinar cell loss – constant feature Islets of Langerhans embedded in

sclerotic tissue & may fuse Eventually islets also disappear Gross – gland is hard with extremely

dilated ducts &visible calcified concretions

Clinical features

Different presentationsrepeated attacks of moderately severe abd.painrecurrent attacks of mild painpersistent abd &back pain

Silent till pancreatic insufficiency & DM develop Recurrent attacks of jaundice or indigestion

Diagnosis

Visualisation of calcifications by CT or USG

Complications

Pseudocyst Malabsorption,steatorrhea Secondary DM Pancreatic carcinoma – 40% risk in

hereditary pancreatitis

GALL BLADDER