DISORDERS OF PANCREAS

(Exocrine)

By
Dr. INDU
17th NOV 2023
 LEARNING OBJECTIVES

1. Describe clinical presentations of Acute pancreatitis and Chronic

pancreatitis

2 . Explain Non neoplastic cysts of the pancreas

3 Describe the Etiopathology of the followings

• Cystic neoplasias of the pancreas
• Pancreatic carcinoma
 PATHOLOGY OF PANCREAS -
EXOCRINE
• CONGENITAL ANOMALIES

• PANCREATITIS

• PANCREATIC NEOPLASMS
 Progressive development (1–4) of the pancreas
and biliary system in weeks 5 - 6 weeks
Exocrine pancreas
80% to 85% Trypsinogen
Acinar cells Chymotrypsinogen
proenzymes
(zymogens)
Activated by
proteolytic cleavage
–
Prophospholipase A GI tract
and B
Procarboxypeptidase
Kallikreinogen
Proelastase
 CONGENITAL ANOMALIES

Pancreas Divisum
• Predisposes to chronic
• Failure of fusion - dorsal and pancreatitis
ventral pancreatic primordia

• Wirsung duct drains only a

portion - Ampulla of Vater
 CONGENITAL ANOMALIES
• Agenesis – PDX1
• Pancreas Divisum
• Annular Pancreas
• Ectopic Pancreas
• Congenital cysta
 CONGENITAL ANOMALIES
Annular
Ectopic Pancreas
Pancreas
• Pancreatic tissue - aberrantly
situated
• Band-like ring of normal
• Stom­ach, duodenum, jejunum,
pancreatic tissue - encircles 2nd Meckel diverticula/ ileum
part duodenum
Pain /localized inflammation/
Duodenal obstruction mucosal bleeding
 ACUTE PANCREATITIS
Acute injury to pancreas due to
autodigestion by digestive enzymes
Acute inflammation of pancreas
• Mechanisms - protect pancreas
• Digestive enzymes - synthesized
zymogens ( Inactive )
• Proenzymes activated – trypsin-
enterokinase - small bowel
• Acinar and ductal cells secrete
trypsin inhibitors - SPINK1
 ACUTE PANCREATITIS

ETIOLOGY PATHOPHYSIOLOGY

• Premature activation of
• Alcohol Trypsinogen – Trypsin
• Gall stones • Autodigestion of pancreas
• Infection/Trauma/Shock
• Drugs – Sulpha drugs
• ERCP
 ACUTE PANCREATITIS

CLINICAL MANIFESTATIONS COMPLICATIONS

Epigastric pain – back DIC /shock

Fever /chills/shock ARDS- phospholipase
Cullen’s and Grey Turner sign Pseudocyst/ Abscess
+ve
 WBC LDH /AST
elevated elevated
Sr.
Amylas
e/Lipas Calciu
e Investigations m
elevate reduced
d
Glucose
elevated BUN
elevated
 ACUTE PANCREATITIS

GROSS HISTOPATHOLOGY
• Focal • Liquifactive necrosis
hemorrhage/Liquifaction • Fat necrosis
• Chalky yellow necrosis – Fat • Acute inflammation
necrosis
 PATHOGENESIS

Gene
Mutation
• PRSS1/SPINK1/CFTR

Gene • Increases the activity

defect of trypsin
Hemorrhage in
the head of the
pancreas
Focal area of
fat necrosis
Fat necrosis on the
(right)
Focal pancreatic
parenchymal
necrosis (centre)
Chronic pancreatitis
• Prolonged
inflammation
• Irreversible destruction
calculi or neoplasms
Middle-aged males; long-term alcohol
abuse
Long-standing
Autoimmune injury
obstruction of the
to the gland (IgG4
pancreatic duct by
related)

• Fibrosis Hereditary
pancreatitis, 25%
• Destruction of Exo
/Endocrine
Morphology ( Chronic pancreatitis)

Fibrosis, atrophy, acinar loss, dilation of

pancreatic ducts

Hard /calcified concretions

Chronic inflammatory infiltrate around lobules

and ducts

The ductal epithelium - atrophied / hyperplastic/

squamous metaplasia
 Chronic malabsorption
Abdominal pain Steatorrea, Vit A /Vit D
Back pain deficiency
Low albumin

Clinical
Manifestations
Pancreatic pseudocysts,-
Weight loss 10%
Edema
Pancreatic cancer
(40% risk in hereditary )
 Chronic
pancreatitis
Chronic
pancreatitis

In Alcohol
abuse:
• Ductal
dilatation
• Intraluminal
protein plugs
• Calcification
 NEOPLASIA BENIGN LESIONS

• Pseudocysts
• Congenital cysts
• Serous cystic neoplasms
• Intraductal papillary mucinous neoplasms and mucinous cystic
neoplasms - precancerous
Pseudocyst
Mucinous cystic neoplasm-
Tail
precursors to invasive carcinomas

Mutations in KRAS oncogene,

TP53 and RNF43 tumor
suppressor genes
 Solid-pseudopapillary neoplasm

Head of pancreas

Mutations in the GNAS and KRAS

oncogenes, TP53, SMAD4
Intra ductal papillary neoplasia
Precursor to Pancreatic Cancer
 PANCREATIC CARCINOMA

Etiology

• Cigarette smoking, double the risk of pancreatic cancer

• Diet rich in fats

• Chronic pancreatitis, DM
 CLINICAL FEATURES

Pain
Obstructive jaundice
Weight loss, anorexia, generalized malaise and
weakness
Signs (Metastasis): Migratory thrombophlebitis -
Trousseau sign, Sister Mary Joseph nodule
Courvoisier Gall bladder, Blumer shelf ( mass in rectal
pouch)
• Precursors to Pancreatic Cancer Pathogenesis
Hard, stellate,
gray-white,
poorly defined
masses
Site: Head
Moderately to poorly
differentiated Adenocarcinoma
 TUMOR MARKERS

Serum carcinoembryonic antigen (CEA) and CA19-9

antigen) - elevated in pancreatic cancer

PRSS1 mutations carry a risk for pancreatic

adenocarcinoma
 SUMMARY
• 80% -85% of pancreas parenchyma has exocrine acinar cells
• Alcohol, drugs, traumatic injury, and viral agents may have a direct injurious
effect on pancreatic exocrine acinar cells - Acute pancreatitis
• Recurrent episodes of acute pancreatitis – Chronic pancreatitis
• Acute pancreatitis causes multiorgan failure if not treated –medical emergency
• Smoking /Chronic pancreatitis – risk factor for adenocarcinoma of pancreas
• KRAS gene mutation – Adenocarcinoma pancreas
An autopsy study of pancreatitis is performed. In some cases, there is
evidence for death from acute pancreatitis in which there are changes of
chronic pancreatitis. Microscopic examination shows acute inflammation,
chronic inflammation with fibrosis and acinar atrophy, and inspissated
protein plugs in small, obstructed pancreatic ducts. Some of the protein plugs
show calcification. What is the most likely risk factor for pancreatitis in these
cases?

(A) Alcohol abuse

(B) Biliary tract lithiasis
(C) Cystic fibrosis
(D) Drug toxicity
(E) Trauma
 Refference
• Robin’s Text book of Pathology ; 10th edition
• WHO Book – Gastro intestinal Tumors
• Wilson C, de Moya M. Cholecystectomy for acute gallstone
pancreatitis: early vs. delayed approach. Scand J Surg. 2010;99:81–85