Diseases of the Pancreas

Dr.CSBR.Prasad, M.D.

Pancreas - Normal anatomy Transversely oriented Retroperitoneal Extends from the duodenum to the splenic hilum 20 cm in length and weighs ~90 gm Separated into four parts: (Based on adjacent

vasculature) Head Neck Body & Tail

Pancreas - Normal anatomyThe pancreatic duct system: highly variable Main pancreatic duct - Wirsung Accessory pancreatic duct - Santorini Ampulla of Vater - common channel for

biliary and pancreatic drainage - The main pancreatic duct joins the common bile duct proximal to the papilla of Vater

Greek word pankreas = “all flesh” Lobulated organ Two components: Exocrine & Endocrine

Exocrine portion – 80% to 85% Endocrine portion – 1%

Pancreas - Normal anatomy

Exocrine portion: Secretes inactive proenzymes

Trypsinogen Chymotrypsinogen Procarboxypeptidase Proelastase Kallikreinogen & Prophospholipase A and B

Pancreas - Normal physiology

Endocrine portion: 1 million, islets of Langerhan Secrete:

Insulin Glucagon & Somatostatin

Pancreas - Normal physiology

Self-digestion of pancreatic tissue is prevented by several mechanisms:   

Enzymes occur as inactive proenzymes The enzymes are membrane-bound Enterokinase is required for activation Trypsin cleaves proenzymes   Trypsin inhibitors in acinar and ductal secretions Acinar cells are resistant to many enzymes

Pancreas - Normal physiology

AGENESIS: PDX1 mutations on chromosome 13qPANCREAS DIVISUM: Most common, 3% to 10%,

chronic pancreatitis ANNULAR PANCREAS: 2nd portion of the

duodenum, duodenal obstruction ECTOPIC PANCREAS: 2% of PMs, stomach and

duodenum, jejunum, Meckel diverticula, and ileum

Pancreas - Congenital Anomalies

Annular pancreas

Pancreatitis Inflammation of the pancreas Injury to exocrine pancreas Severity may range form mild self limiting

illness to life threatening acute inflammatory process

Pancreatitis Acute pancreatitis: Reversible

Gland returns to normal if underlying pathology is removed

Chronic pancreatitis: IrreversibleBy definition it’s irreversible loss of

exocrine parenchyma

Acute Pancretitis Reversible pancreatic parenchymal injury

associated with inflammation M:F = 1:3 (with biliary tract disease 6:1) Biliary tract disease & gall stones account

for 80% of cases Alcohol binge as precipitant – vary 60% in

some places to 5% in other areas

Etiologic Factors in Acute PancreatitisMetabolic alcoholism

hyperlipoproteinemias

hypercalcemia

Drugs (azathioprine)

Genetic Mutations in cationic tryprinogen and trypsinogen inhibitor gene

Mechanical Gall stones

Trauma

Operative procedures

Vascular shock

Atheroembolism

vasculitis

Infections mumps

Etiologic Factors in Acute Pancreatitis – less common causes

Ampullary carcinomasAscaris lumbricoidesClonarchis sinensisHereditory pancreatitis

Hereditary Pancreatitis Recurrent attacks of severe pancreatitis Begins in childhood Most of them are due to genetic mutations Trypsinogen gets activated with in the

pancreas

Acute pancreatitis - MorphologyThe basic alterations are: Microvascular leakage causing edema Necrosis of fat by lipolytic enzymes Acute inflammation Proteolytic destruction of pancreatic

parenchyma and Destruction of blood vessels and subsequent

interstitial hemorrhage

Fat necrosis Foci of fat necrosis may also be found in

extra-pancreatic collections of fat Omentum Mesentery of the bowel Subcutaneous fat

Chicken soup exudate In the majority of cases the peritoneal

cavity contains a serous, slightly turbid, brown-tinged fluid in which globules of fat can be identified

In its most severe form, hemorrhagic pancreatitis, extensive parenchymal necrosis is accompanied by dramatic hemorrhage within the substance of the gland

Red-black hemorrhage interspersed with foci of yellow-white, chalky fat necrosis

PathogenesisAutodigestion of the pancreatic substance by

inappropriately activated pancreatic enzymes

PathogenesisInappropriate activation of trypsinogen is an

important triggering event in acute pancreatitis

Pathogenesis Inappropriate activation of Trypsin With resultant activation of other

proenzymes Prekallikrein (kinin system) Hageman factor (Clotting, compliment sys)

Pathogenesis - AlcoholismAlcohol consumption may cause pancreatitis

by several mechanisms:1 - Secretion of protein-rich pancreatic fluid2 - Increases pancreatic exocrine secretion3 - Contraction of the sphincter of Oddi and 4 - Direct toxic effects on acinar cells

Clinical features:1 Pain abdomen2 Anorexia, nausea, and vomiting 3 leukocytosis, hemolysis, disseminated

intravascular coagulation, 4 Fluid sequestration5 ARDS6 diffuse fat necrosis. 7 Peripheral vascular collapse and shock8 acute renal tubular necrosis

Lab findings:1 Elevated Serum amylase (with in 24hrs) 2 Lipase (72hrs)3 Glycosuria4 Hypocalcemia (poor prognosis)

Macroamylasemia Normal persons with high serum amylase Because of large size they can not be

excreted in urine May be mistaken for acute pancreatitis

Chronic Pancreatitis

Recurrent bouts of inflammation leads to loss of pancreatic parenchyma and replacement by fibrosis

Primary causes: Alcohol abuse Hypercalcemia / hyperlipoproteinemia Pancreas divisum Hereditary pancreatitis

Chronic Pancreatitis

Chronic Pancreatitis - Pathology Loss of lobular appearance of pancreas

Loss of exocrine tissue (typically not islets) Irregularly distributed fibrosis Reduced size of pancreas Inflammation Destruction of ducts – ductal dilatation Pseudocysts (25% of cases)

Chronic Pancreatitis - Gross

NormalWhite areas of fibrosis

Chronic Pancreatitis- Micro

Normal

Sequelae - Acute Pancreatitis Systemic complications

Shock Organ failure

DIC Pancreatic abscesses Pseudocysts Duodenal obstruction

Sequelae - Chronic Pancreatitis Duct obstruction Pseudocysts Malabsorption (Steatorrhea, Vit deficiency) Secondary diabetes

Pancreatic Pseudocysts Localized collections of pancreatic secretions (within or adjacent to pancreas) Virtually all arise after a bout of acute or chronic pancreatitis Lack a true epithelial lining

Lined by macrophages, fibrosis Different from sterile pancreatic abscesses

Collections of neutrophils following liquefactive necrosis of pancreatic parenchyma

Pancreatic Pseudocyst - Gross

Pancreatic Pseudocyst - Micro

Pancreatic Pseudocyst

vs. congenitalcyst

Cullen’s sign

Grey-Turner’s sign

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