B65 Pancreatitis

Question 1

Causes of acute pancreatitis

Answer 1

80% are from alcoholism or gall stones - obstruction of a duct.

30-60% gall related overall. In the US, 65% are from alcoholism.

other causes:

• Trauma
• Surgery
• Hypercalcemia
• Hyperliproteinemia
• Other vater papilla obstruction
  
  • pancreatic head tumor
  • ascaris lumbricoides infection
• Viral infections - mumps, coxsackie, hep B
• Iatrogenic
  
  • Many different mediactions present risk
  • from ERCP
• 10-20% are idiopathic

Question 2

Mutations that predispose to acute pancreatitis

Answer 2

Autosomal dominant disease hereditary pancreatitis: Trypsinogen mutations. Cause recurrent acute pancreatitis from childhood.

Causes not only trypsin hyperactivation, but trypsin catalyzes the activation of many other pancreatic digestive enzymes.

Other gene mutations that predispose:

• Trypsin inhibitor gene.
• other pancreatic enzymes or inhibitors.

Question 3

What are the types of acute pancreatitis?

Answer 3

Interstitial edematic, this is the initial mild form of acute pancreatitis

and

Hemorrhagic necrotizing, the late, severe form which is life threatening, severe bleeding and systemic release of lipases, causing systemic membrane damae. Lipases released into the abdominal cavity during hemorrhage can cause fat necrosis of the bowel omentum and mesentery.

Question 4

What is the morphological progression of damage to the pancreas during acute pancreatitis?

Answer 4

1. Microvascular leakage causing edema
2. Necrosis of fat by lipases
3. Acute inflammatory reaction
4. Destruction of the pancreatic parenchyma
5. Destruction of blood vessels leading to interstitial hemorrhage.

Question 5

Describe the pathogenesis of acute pancreatitis

Answer 5

The key moment is the inappropriate activation of trypsin within the pancreas, triggering further activation of itself and other enzymes. Causing autodigestion of the pancreas by its enzymes.

Trypsin also converts Prekallikrein to kallecrein, which activates bradykinin, and increases blood flow, contributing to hemorrhage.

Duct obstruction:

• Pancreatic lipase is secreted in an active form.
• Stasis can cause local fat necrosis, and the injured tissue stimulate inflammation. Nonspecific inflammtory damage,
• Edema and compromised blood flow
• Ischemic injury to acinar cells, disrupted membranes, release of and actrivation of trypsin.

Primary acinar cell injury:

• Ichemia
• viral infection
• drugs
• pancreatic trauma

Alcohol

• Increases pancreatic exocrine (digestive enzyme) secretion
• Also increases the contration, tone of the sphincter of Oddi.
• Direct toxic effects on acinar cells, increasing oxidative stress and membrane damage
• Increases viscocity of pancreatic excretion, leading to protein plugs and duct obstruction.

Defective intracellular transport of proenzymes in acinar cells.

• inappropriate fusion of proenzyme granules with lysosomes containing hydrolases that activate them.
• As of now this has only been demonstrated in animal models.

Question 6

Presentation and symptoms of acute pancreatitis

Answer 6

Acute abdominal pain is the cardinal symptom. Can be mild or severe and incapacitating. Pain radiates to the upper back.

Acute abdomen in severe cases - abdominal guarding, severe pain, and ominous lack of bowel sounds.

Elevated plasma amylase and lipase - Amylase rises first, within 24 hours. Lipase within 72 - 96 hours, but lipase is more specific.

Nausea and vomiting

Periumbilical hemorrhage, and flank hemorrhage. As bleeding into the retroperitoneum occurs, and blood moves forward into the periumbilical soft tissue.

Hypocalcemia as calcium is consumed during saponification in fat necrosis. Development of hypocalcemia is a bad prognositic sign.

80% of acute pancreatitis cases are mild and self limiting (don’t pregress beyond the edematous, interstitial phase) 20% are severe and are an urgent medical emergency

Question 7

What are the systemic effects and consequences of a severe acute pancreatitis?

Answer 7

Autodigestion of the pancreas with severe necrosis and hemorrhage.

Hemorrhage into the retroperitoneal space, severe blood loss and Hypovolemic shock

Systemic release of active lipases to the blood, and systemic endothelial damage.

• Disseminated Intravascular Coagulation
• Acute Respiratory Distress Syndrome
• Peripheral vascular collapse and Distributive shock
• Bacteremia, septicemia from GI wall breakdown
• Renal failure from acute tubular necrosis.

Question 8

Describe pancreatic pseudocysts and how they form.

Answer 8

Commonly following acute pancreatitis, especially alcoholic pancreatitis

Formed after necrotic areas of the pancreas are removed. Fill with fluid that is rich in pancreatic enzymes.

They usually spontaneously resolve, but can become secondarily infected, or can compress adjacent structures, more risk for acute pancreatitis.

Question 9

How is acute pancreatitis treated?

Answer 9

Supportive therapy, maintain blood pressure, alleviate pain

limit pancreatic secretions by total restriction of blood and fluid intake.

in ~50% of necrotizing pancreatitis, it will become infected by something from the GI tract, and this may require treatment.

sterile or infected abscesses or pseudocysts will develop in the pancreas after recovery.

5% die from shock in the 1st week of illness.

Question 10

Chronic pancreatitis, basic distinction between acute pancreatitis

Answer 10

a) Longstanding inflammation and fibrosis of the pancreas with destruction of the exocrine pancreas; in late stages, endocrine parenchyma is also lost.
b) The chief distinction of acute and chronic pancreatitis is irreversible impairment in pancreatic functioning in chronic pancreatitis, as the pancreas in acute pancreatitis can return to normal if the underlying mechanism is removed.

Question 11

Morphology of chronic pancreatitis

Answer 11

From long term alcohol abuse

• parenchymal fibrosis
• reduced number and size of acini, acinar loss is a main feature
• variable dilation of the pancreatic ducts;
• Chronic inflammatory infiltrate usually present around remaining lobules and ducts
• Ducts can be: atrophied, hyperplastic, squamous metaplasia may occur, concretions may be present.
• Remaining Islets of langerhans often fuse and appear enlarged, eventually these are lost as well.
• The gland is hard, with often visible calcifications and dilated ducts

Autoimmune pancreatitis

• Presents as one of two distinct patterns
• Lymphoplasmacytic sclerosing pancreatitis
  
  • ​Striking infiltration by plasma cells and lymphocytes
• Idiopathic duct centric pancreatitis
  
  • ​Infiltration of nuetrophils, lymphocytes, and plasma cells, centered around the ductal epithelium.

Question 12

Causes of chronic pancreatitis

Answer 12

Chronic alcoholism

other causes:

• long standing obstruction, stones, neoplasms,
• tropical pancreatitis, seen in asia and africa with unclear cause, genetic suspected
• Hereditary pancreatis, due to the trypsin mutations, and repeated small areas of acute pancreatitis
• Cystic fibrosis associated chronic pancreatitis, and non-CF germline mutations to the CFTR gene.

Question 13

Pathogenesis of chronic pancreatitis

Answer 13

Ductal obstruction by concretions.

Toxic-metabolic.

Oxidative stress.

• Ductal obstruction by concretions. Many of the
inciting agents in chronic pancreatitis (e.g., alcohol)
increase the protein concentration of pancreatic secretions,
and these proteins can form ductal plugs.
• Toxic-metabolic. Toxins, including alcohol and its
metabolites, can exert a direct toxic effect on acinar cells,
leading to lipid accumulation, acinar cell loss, and eventually
parenchymal fibrosis.
• Oxidative stress. Alcohol-induced oxidative stress may
generate free radicals in acinar cells, leading to membrane
damage (Chapter 1), and subsequent expression of chemokines
like interleukin-8 (IL-8), which recruits mononuclear
inflammatory cells. Oxidative stress also promotes
the fusion of lysosomes and zymogen granules with resulting

Question 14

Presentation of chronic pancreatitis

Answer 14

May present with repeated bouts of jaundice.
vague persistent digestion problems.
recurrent abdominal and back pain.
it may be entirely silent until pancreatic insufficiency and diabetes mellitus develop.

calcifications in the pancreas on imaging.

malabsorption syndrome

diabetes mellitus