Disorders of the pancrease.

1. Disorders of pancrease
Anatomy & physiology
Cystitis fibrosis
Pancreatitis (acute &chronic)

2. Anatomy & physiology of pancreas
● histologically and physiologically has 2 distinct parts—the exocrine and endocrine parts
● exocrine and endocrine, is embryologically derived from the foregut endoderm
● pancreas lies obliquely in the concavity of the duodenum as an elongated structure about 15 cm in length and 100 gm in weight
● It lies in the epigastrium & the left upper quadrant
● Situated on the posterior abdominal wall behind the peritoneum.
● 3 topographic zones:
○ The head lying in the concavity of the duodenum and the uncinate process projecting from the head.
○ The neck lies in front of the beginning of the portal vein and origin of the superior mesenteric A.
○ The body comprises the main part of the gland.
○ The tail is the thin, tapering part of the gland towards the hilum of the spleen
● exocrine pancreas constitutes 80 to 85%- produces secretion that contains enzymes capable of hydrolysing protein, fat and carbohydrates-
alkaline secretion of digestive enzymes prominent among which are trypsin, chymotrypsin, elastase, amylase, lipase and phospholipase
● An endocrine is 15-20% -produces the hormones insulin(B cells) & glucagon(A cell) (metabolism of carbohydrate), somatostatin (d cell) &
pancreatic polypeptide (PP cells)
● Supply blood- splenic, superior &inferior pancreaticoduodenal A. lymph drainage – celiac &superior mesenteric nodes. Nerve –vagal nerve Fibers
(sympathetic parasympathetic )

3. Congenital anomalies
●Annular pancreas- Annular pancreas is a rare birth defect that affects the pancreas. It occurs when a ring of
extra pancreatic tissue encases the first part of the small intestine (duodenum). This can cause several
symptoms, including vomiting, abdominal distention, and intolerance to food.
○ Gross: encirclement of duodenum by pancreatic parenchyma leads to constriction of duodenal lumen
○ Microscopic contains large number of PP cells in its many irregularly shaped islets.
●Heterotopic pancreas- also known as Ectopic pancreatic tissue, refers to the presence of pancreatic tissue
in the submucosal, muscularis or subserosa layers of the luminal gastrointestinal tract outside the normal
confines of the pancreas and lacking any anatomic or vascular connection with the pancreas proper.

4. Cystic Fibrosis
●hereditary disorder characterized by viscid mucous secretions in all the exocrine glands of the body (muco-
viscidosis) and associated with increased concentrations of electrolytes in the eccrine glands.
●transmitted as an autosomal recessive trait with apparent clinical features in homozygotes only. defect is a
genetic mutation in CFTR gene, acronym for coding protein for cystic fibrosis transmembrane conductance
regulator located on chromosome 7
●Common in whites, clinical presentation may appear at birth or adolescent
●pertain to multiple organs and systems such as pancreatic insufficiency, intestinal obstruction, steatorrhea,
malnutrition, hepatic cirrhosis and respiratory complications. When it affects the lungs, it can cause the COPD

5. Etiology
● The abnormal CFTR protein in patients with CF leads to disruption of chloride channels on the cells. Cause
the sweat to become very salty.
● Defective chloride transport cause more water and sodium reabsorption than normal.
● Secretion in affected organs becomes thick and viscous causing obstructing the glands and ducts.
● Dilatation of secretory glands >damage to the exocrine tissues
● The hallmark pathophysiologic effects of CF includes
● Excessive mucous production in the respiratory tractwith impaired ability to clear secretion and
progressive COPD: atelectasis, infection, bronchiectasis, dilation of distal airways, chronic hypoxemia,
acute or chronic liver damage.
● Pancreatic enzyme deficiency and impaired digestion, pancreatic insufficiency and impaired enzymes
secretion >impaired digestion and absorption of proteins, carbohydrate &fat. Degenerative and fibrotic
change>DM

6. Morphological features
●Pancreases- gross – pancreas lobules are ovoid rather than rhomboid. Fatty replacement of the pancreas and grossly visible
cysts may be seen
●Microscopically, the lobular architecture of pancreatic parenchyma is maintained. There is increased interlobular fibrosis.
The acini are atrophic and many of the acinar ducts contain laminated, eosinophilic concretions. Rarely, inflammation, fat
necrosis and cyst formation may be seen. The islet tissue (endocrine pancreas) generally remains intact. Atrophy of the
exocrine pancreas may cause impaired fat absorption, steatorrhoea, intestinal obstruction and avitaminosis A.
●Liver. The bile canaliculi are plugged by viscid mucous which may cause diffuse fatty change, portal fibrosis and ductular
proliferation. More severe involvement may cause biliary cirrhosis
●Respiratory tract. Changes in the respiratory passages are seen in almost all typical cases of cystic fibrosis. The viscid
mucous secretions of the submucosal glands of the respiratory tract cause obstruction, dilatation and infection of the
airways. The changes include chronic bronchitis, bronchiectasis, bronchiolitis, bronchiolectasis, peribronchiolar pneumonia
and inflammatory nasal polyps
●Salivary glands. Pathologic changes in the salivary glands are similar to those in pancreas and include obstruction of the
ducts, dilatation, fibrosis and glandular atrophy.
● Sweat glands. Hypersecretion of sodium and chloride in the sweat observed in these patients may be reflected
pathologically by diminished vacuolation of the cells of eccrine glands.

7. Clinical manifestations
● Pulmonary manifestation
○ Productive cough
○ Wheezing
○ Hyperinflation of lung fields(X-ray)
○ Infections and shortness of breath
○ PFT results consistent with obstructive airways diseases
○ Enlarged heart
● Non pulmonary manifestations
○ GIT (pancreatic insufficiency, recurrent abdominal pain)
○ Biliary cirrhosis
○ Vit. Deficiencies (ADEK)
○ Protein and fat malabsorption
○ Recurrent pancreatitis
○ Weight loss
○ Infertility
○ Meconium ileus in newborn babies
○ Clubbig of the extremities
○ Salty tasting skin
○ Poor growth and poor weight gain

8. Assessment and diagnostic finding
●Sweat chloride concentration test:
○Sweat test- sweat chloride values of >60 mEq/L
○Genetic test find out what type of CFTR defect is causing CF
○Chest X-ray: inflated lung, lungs fibrosis and searing.
○Lung function test
○Sputum culture
○Liver function test

9. Pancreatitis (acute &chronic)
●inflammation of the pancreas with acinic cell injury
●Acute pancreatitis- present clinically with acute abdomen and is associated with macroscopic hemorrhages
and fat necrosis.
●Onset is sudden, occurs after a bout of alcohol or heavy meal
●Clinical presentation- abdominal pain(epigastric –radiating to the back), vomiting and collapse
●DDX- acute appendicitis, perforated Peptic ulcer, acute cholecystitis, infraction of intestine (sudden
occlusion of mesenteric vessels).
●There is elevation of serum amylase with first 24hrs and serum lipase level after 3-4 days
●Glucosuria occurs in 10% of cases

10. Etiology
●Leading causes alcoholism and cholelithiasis in >80% of cases
●Less common- trauma, ischaemia, shock, extension of inflammation from the adjacent tissues, bloodborne
bacterial infection, viral infections, certain drugs (e.g. thiazides, sulfonamides, oral contraceptives, methyl
dopa, procainamide, furosemide), hypothermia, hyperlipoproteinemia and hypercalcaemia from
hyperparathyroidism.
●Other case are idiopathic while rarely familial.

11. Pathogenesis
●3 main groups of enzymes which bring about destructive effects on the pancreas are as under:
○ Proteases such as trypsin and chymotrypsin play the most important role in causing proteolysis. Trypsin also activates the
kinin system by converting prekallikrein to kallikrein, and thereby the clotting and complement systems are activated. This
results in inflammation, thrombosis, tissue damage and haemorrhages found in acute haemorrhagic pancreatitis.
○ Lipases and phospholipases degrade lipids and membrane phospholipids.
○ Elastases cause destruction of the elastic tissue of the blood vessels.
●The activation and release of these enzymes is brought about by one of the following mechanisms:
●Acinic cell damage caused by the etiologic factors such as alcohol, viruses, drugs, ischaemia and trauma result in
release of intracellular enzymes.
●Duct obstruction caused by cholelithiasis, chronic alcoholism and other obstructing lesions is followed by
leakage of pancreatic enzymes from the ductules into the interstitial tissue.
●Block in exocytosis of pancreatic enzymes occurring from nutritional causes results in activation of these
intracellular enzymes by pancreatic lysosomal hydrolases.

12. MORPHOLOGIC FEATURES
●Grossly, in the early stage, the pancreas is swollen and oedematous. Subsequently, in a day or two,
characteristic variegated appearance of grey-white pancreatic necrosis, chalky-white fat necrosis and blue-
black haemorrhages are seen. In typical case, the peritoneal cavity contains blood-stained ascitic fluid and
white flecks of fat necrosis in the omentum, mesentery and peripancreatic tissue. The resolved lesions show
areas of fibrosis, calcification and ductal dilatation.
●Microscopically, the following features in varying grades are noticeable:
○ Necrosis of pancreatic lobules and ducts
○ Necrosis of the arteries and arterioles with areas of haemorrhages.
○ Fat necrosis.
○ Inflammatory reaction, chiefly by polymorphs, around the areas of necrosis and haemorrhages

13. Clinical presentation
●Constant severe epigastric pain-radiating towards back, worsen after meals or supine, improves on leaning forwards
●Nausea, vomiting
●GE- signs of shock- tachycardia, hypotension, oliguria/anuria. Possible Jaundice (biliary pancreatitis)
●Abd. Exam- tenderness, distention, guarding, ileus, reduced bowel sounds/ tympany, ascite
●Skin changes (rare)- Cullen’s sign(periumbilical ecchymosis and discoloration), grey turners’s sign (flank ecchymosis with
discoloration), fox’s sign: ecchymosis over the inguinal ligament.
●Diagnosis – abd pain, serum lipase or amylase activity >3x upper limit and CT findings.
●CBC- Haematocrit- acute haemorrhagic pancreatitis, WBC count- leucocytosis-severe
●BUN- raising blood urea nitrogen levels after >48 of resuscitation( persistent third spacing of fluid)
●Increased CRP levels >120-150mg/L & procalcitonin levels –necrotizing
●Increased ALT levels(>150 U/L- biliary pancreatitis.
●Alkaline phosphatase, bilirubin levels – gallstone pancreatitis
●Serum calcium levels and serum triglyceride level (fasting)
●Ultrasound , CT Scan

14. Complications
●Systemic complications:
○Chemical and bacterial peritonitis
○Endotoxic shock
○Acute renal failure
●Local sequelae:
○Pancreatic abscess
○Pancreatic pseudocyst
○Duodenal obstruction
●Mortality in acute pancreatitis is high (20-30%). Patients succumb to hypotensive shock, infection, acute
renal failure, and DIC.

15. Chronic Pancreatitis
●Characterized by repeated bouts of mild to moderate pancreatic inflammation, with continued loss of pancreatic
parenchyma and replacement by fibrous tissues.
●Present recurrent attacks of severe abdominal pain at intervals of months to years, weight loss and jaundice. Later DM
& steatorrhoes
●Abdominal radiographs show calcification in the region of pancreas and presence of pancreatic calculi in the ducts.
●Etiologic factors
○Obstruction of the ductal system by carcinoma or stone
○Alcoholism
○Hyperparathyroidism
○Polyarteritis nodasa
○Mumps, Tb, sarcoidosis.

16. MORPHOLOGIC FEATURES
●Grossly, the pancreas is enlarged, firm and nodular. The cut surface shows a smooth grey appearance with
loss of normal lobulation. Foci of calcification and tiny pancreatic concretions to larger visible stones are
frequently found. Pseudocysts may be present.
●Microscopically, depending upon the stage of development, the following changes are seen:
○ Obstruction of the ducts by fibrosis in the wall and protein plugs or stones in the lumina
○ Squamous metaplasia and dilatation of some interand intralobular ducts
○ Chronic inflammatory infiltrate around the lobules as well as the ducts
○ Atrophy of the acinar tissue with marked increase in interlobular fibrous tissue
○ Islet tissue is involved in late stage only.

17. Investigation
●Serum pancreatic enzyme level- lipase and amylase are normal
●Pancreatic function tests ( direct and indirect)
●Cholecystokinin test
●Secretin
●Cholecystokinin-secretin test
●Fecal elastase-1 activity- confirms steatorrhea
●Abdominal x-ray

18. Complication
●Pancreatic insufficiency
●Splenic vein thrombosis
●Pseudocyst
●Ascites
●DM
●Bile duct obstruction
●Duodenal obstruction
●Pancreatic adenocarcinoma
●DDX