1. Lecture 36- Pancreatitis
a. Define
b. Discuss the causes and clinical features
c. Describe the morphological changes. A

2. Pancreatitis
Pancreatitis is inflammation of the pancreas a\w injury to the exocrine parenchyma.
Normally digestive enzymes secreted by the pancreas are not active until they reach the intestinal tract.
When the pancreas is inflamed, the enzymes attack and .damages the tissue that produce them.
Duration of the disease can range different from:
a transient attack to a permanent loss of function.
Classified into to form:
Acute pancreatitis- usually reversible
Chronic pancreatitis- irreversible.
The clinical manifestations range in severity from:
Mild, Self-limited disease to a life-threatening acute inflammatory process.

3. What is acute pancreatitis?
Acute pancreatitis is in most instances a sterile (noninfectious) chemically mediated inflammation of the pancreas resulting from injury of the exocrine pancreas.
Reversible if the underlying cause is removed.
Patients typically present with: Epigastric pain with radiation to the back a\w increased pancreatic enzymes:
(Amylase, trypsin and Lipase) in blood or urine.
Biliary tract disease and alcoholism account for approximately 80% of cases in West.

4. What is acute pancreatitis?
It occurs in two forms:
Interstitial or edematous pancreatitis: Mild inflammation with edema & widening of interstitial spaces. No or only minor necrosis.
Mild elevation of pancreatic enzymes in blood.
It requires no treatment and heals spontaneously.
2. Acute hemorrhagic pancreatitis: Severe and life-threatening condition, which is not common. “Pancreatic& peripancreatic”
Prominent enzyme-mediated destruction.

5. Etiologic Factors in Acute Pancreatitis
>than 85 drugs , furosemide, ER
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6. Pathogenesis of acute pancreatitis
Pancreatic duct obstruction  edema  compression of blood vessels  ischemia  acinar cell injury.
Acinar cell injury  release of pancreatic & lysosomal enzymes  activation of enzymes  autodigestion of pancreas.
Defective intracellular transport of proenzymes within acinar cells.
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7. The morphology of acute pancreatitis
Acute inflammation.
Microvascular leakage causing edema.
Enlargement.
Proteolytic destruction
Destruction of blood vessels and subsequent interstitial hemorrhage.
Necrosis of fat by lipolytic enzymes.
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8. Fat necrosis- white chalky deposits
45years old male subjected to abdominal direct trauma, followed by sever abdominal pain- operation findings?
Fat necrosis- white chalky deposits

9. Fat necrosis Fat necrosis, results from enzymatic activity of lipase.
The released fatty acids combine with calcium to form insoluble salts that impart a granular blue microscopic appearance to the fat cells.
Acute necrotizing pancreatitis, acinar and ductal tissues as well as the islets of Langerhans are necrotic.
Fall 10

10. Clinical findings of acute pancreatitis
is a medical emergency ”acute abdomen”.
All cardinal manifestation of acute inflammation.
Acute pancreatitis attributed to release of toxic enzymes, cytokines, and other mediators.
Patients present with:
Severe, mid-epigastric pain with radiation to the upper back “band-like”.
Fever, nausea and vomiting.
Peripheral vascular collapse and shock.
Cullen sign & Grey Turner sign
Paralytic ileus “no bowel sound heared”.
boring, midepigastric pain with radiation to the back
Radiation into the back is due to its retroperitoneal location.
Shock:
Due to hemorrhage and loss of enzyme rich fluid around the pancreas ( called “third spacing”)

11. Grey Turner sign Cullen’s sign
( flank hemorrhage),
(periumblical hemorrhage),

12. Investigations Increased serum lipase (MORE SPECIFIC)-72-96hrs.
Increased serum & urinary amylase (less specific)- 24 hrs.
Other causes of hyperamylasemia include: Mumps,small bowel infarction and a ruptured ectopic pregnancy.
CBC: Neutrophilic leukocytosis.
Serum calcium: Hypocalcemia.
Blood glucose: Hyperglycemia (destruction of beta islet cells).
LFT: Bilirubin, AST
CT scan is the gold standard for pancreatic imaging- enlarged inflamed pancreas.
Endoscopic retrograde cholangiopancreatography
An increase in amylase is not specific for pancreatitis.
Other causes of hyperamylasemia include
Mumps,small bowel infarction and a ruptured ectopic pregnancy.

13. Diagnostic criteria
Two of the following three are required to make a diagnosis:
(1) Typical abdominal pain; (band-like)
(2) Threefold or more elevation of pancreatic enzyme values in the blood;
(3) Inflammation of the gland on computed tomography (CT) scan or magnetic resonance imaging (MRI) scan.
Fall 10
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14. Complications Tetany: Pancreatic pseudocyst:
Hypocalcemia is caused by enzymatic fat necrosis
Calcium binds to fatty acids leading to a decrease in ionized ca+.
Pancreatic pseudocyst:
Collection of digested pancreatic tissue around pancreas.
Pancreatic abscess: high mortality unless drained
ARDS with hypoxemia, may occur.
Circulating pancreatic phopholipase destroys surfactant
Loss of surfactant produces atelectasis.
Hemorrhagic ascites
Haemolysis and DIC.
Shock with acute renal tubular necrosis & failure.
Hypoxemia:
Circulating pancreatic phopholipase destroys surfactant
Loss of surfactant produces atelectasis and intrapulmonary shunting
Grey-Turner’s sign ( flank hemorrhage), Cullen’s sign (periumblical hemorrhage)
Pancreatic pseudocyst
Collection of digested pancreatic tissue around pancreas
Abdominal mass with persistence of serum amylase longer than 10 days
Pancreatic abscess:
high mortality unless drained
ARDS with hypoxemia
Left sided pleural effusion:
contains amylase
Hypocalcemia
from enzymatic fat necrosis

15. Chronic pancreatitis Is characterized by:
is defined as chronic inflammation of the pancreas with irreversible destruction of exocrine parenchyma. .
Is characterized by:
Secondary to repeated bouts of pancreatitis.
Chronic inflammatory cells infiltrates
Atrophy, fibrosis and concretion.
Cystic dilatation and clacification.
Loss& atrophy of endocrine acini, ”islets”-late.
Commonly a\w Alcohol abuse.
Results in pancreatic insufficiency:
Steatorrhea,
Fat soluble vitamin deficiency (A,D,E& K).
Diabetes mellitus.
Major differences in acute and chronic pancreatitis:
Acute pancreatitis: reversible if inciting stimulus is withdrawn
Chronic pancreatitis: irreversible destruction of exocrine pancreas
Pancreatic inflammation with destruction of exocrine pancreas and fibrosis
Late stages there is destruction of endocrine pancreas
Majority of cases are idiopathic
Known causes:
Alcohol abuse is MC known cause
Cystic fibrosis is MC cause in children
Repeated attacks of acute pancreatitis produce
duct obstruction and
Calcified concretions in pancreas
May be silent or present with recurrent attacks of
Severe pain radiating into the back
Attacks precipitated by alcohol abuse, overeating.
Malabsorption (due to loss of exocrine pancreas)
Type I DM (due to loss of endocrine pancreas)

16. Etiology of Chronic pancreatitis
Long-standing obstruction of the pancreatic duct by pseudocysts, calculi, trauma, neoplasms.
Long-standing exposure to toxin or alcohol. [Alcohol thickens ductal secretions. Also increases duct permeability to enzymes]. [70%]
Tropical pancreatitis, heterogeneous disease (Africa and Asia), a few cases have a genetic basis.
Hereditary pancreatitis.
CFTR gene mutations-
Activation of pancreatic proenzymes.
Activation leads to autodigeston of pancreas
Mechanism of activation of pancreatic proenzymes:
Obstruction of the main pancreatic duct or terminal CBD
Gallstones
Alcohol thickens ductal secretions
Also increases duct permeability to enzymes
Chemical injury of acinar cells
Examples-thiazides, alcohol, triglyceride (>1000 mg/dL)
Infectious injury of acinar cells
Examples-CMV, mumps, coxsackievirus
Mechanical injury of acinar cells
Examples-seat belt trauma, posterior penetration of duodenal ulcer
Metabolic activation of proenzymes (e.g., hypercalcemia, ischemia, shock)

17. Pathogenesis of Chronic pancreatitis
Pathogenesis of acute pancreatitis:
Ductal obstruction by concretions  increase protein concentrations in the pancreatic juice (alcohol)
Alcohol: thickens ductal secretions.
Toxic effects-direct effect of toxin& alcohol.
Oxidative stress. Alcohol-induced oxidative stress may generate free radicals in acinar cells, leading to membrane lipid oxidation.
Activation of pancreatic proenzymes.
Activation leads to autodigeston of pancreas
Mechanism of activation of pancreatic proenzymes:
Obstruction of the main pancreatic duct or terminal CBD
Gallstones
Alcohol thickens ductal secretions
Also increases duct permeability to enzymes
Chemical injury of acinar cells
Examples-thiazides, alcohol, triglyceride (>1000 mg/dL)
Infectious injury of acinar cells
Examples-CMV, mumps, coxsackievirus
Mechanical injury of acinar cells
Examples-seat belt trauma, posterior penetration of duodenal ulcer
Metabolic activation of proenzymes (e.g., hypercalcemia, ischemia, shock)

18. Fall 10
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19. Clinical features Laboratory and radiographic findings:
Repeated attacks of mild, moderate or persistent abdominal pain, with back pain.
DM developed.
Attacks of jaundice- Gallstone-induced obstruction.
Weight loss and hypoalbuminemic edema -malabsorption caused by pancreatic exocrine insufficiency.
Pancreatic pseudocysts 10%, CANCER 40%.
Increased amylase- elevated “During the attack”.
Alkaline phosphatase- elevated.
Jaundice (increase serum bilirubin ).
Pancreatic calcifications (CT scan best study)
Activation of pancreatic proenzymes.
Activation leads to autodigeston of pancreas
Mechanism of activation of pancreatic proenzymes:
Obstruction of the main pancreatic duct or terminal CBD
Gallstones
Alcohol thickens ductal secretions
Also increases duct permeability to enzymes
Chemical injury of acinar cells
Examples-thiazides, alcohol, triglyceride (>1000 mg/dL)
Infectious injury of acinar cells
Examples-CMV, mumps, coxsackievirus
Mechanical injury of acinar cells
Examples-seat belt trauma, posterior penetration of duodenal ulcer
Metabolic activation of proenzymes (e.g., hypercalcemia, ischemia, shock)
Laboratory and radiographic findings: