Acute Pancreatitis

00:01 Welcome. In this talk, we're going to discuss acute pancreatitis.

00:06 Simply put, this is inflammation of the pancreas. There are a variety of causes that we'll talk about.

00:11 The epidemiology overall in the United States about 50 cases per 100,000 adults each year.

00:18 Worldwide, somewhere in that same range.

00:22 Men are more frequently affected than women and this is probably because of excess alcohol intake by men relative to women, so 6:1 ratio for alcohol related causes of acute pancreatitis.

00:34 Wherein with biliary disease, gallstones or things like that, it's going to be more frequent that it involves females.

00:41 So, a number of things can lead to this, so biliary tract disease is probably the most common cause, about 40% of cases due to stone impacting in the common bile duct or at the point where say the duct of Wirsung dumps into the ampulla of Vater in the duodenum.

00:59 Alcohol is going to be about 30% of cases. It's idiopathic.

01:03 In another 20% of cases, this may actually be due to microlithiasis, so sludging within the drainage of the pancreas.

01:14 Certain drugs will tend to be associated with pancreatitis probably because of abnormal activation of intracellular proteases and lipases within the exocrine pancreas.

01:26 Injury and this can be trauma directly or can be iatrogenic such as an endoscopic retrograde cholangiopancreatography damaging the, say the ampulla of Vater and then causing edema and obstruction.

01:43 Other causes include infection such as mumps, Coxsackie. Autoimmune pancreatitis is a cause. Annular pancreas is a cause.

01:52 Elevated levels of calcium can be a cause for pancreatitis by causing abnormal flow of pancreatic juices and inappropriate activation of those enzymes within the pancreas.

02:03 And then there are genetic causes with mutations either in trypsin or trypsin-inhibitor molecules, so too much activation of trypsin or insufficient inhibition.

02:13 Cystic fibrosis by virtue of the fact that it causes sluggish pancreatic secretions will also lead to inappropriate activation of the pancreatic enzymes and can be a cause for chronic pancreatitis.

02:26 The pathophysiology. As I've already intimated, there are a number of causes.

02:31 This is just showing you an image with a gallstone impacted at the ampulla of Vater.

02:36 This is going to obstruct flow down the pancreatic duct and we will have a regurgitation, a backflow in accumulation so that we are getting activation of the enzymes that are normally in the pancreatic juices that leads to destruction of membranes and cells of the duct itself and in vessels so you end up with an inflamed damaged pancreas and the ensuing edema as well as the release of pancreatic enzymes just makes matters worse.

03:08 This schematic shows a number of other pathways that may be involved in driving the development of pancreatitis.

03:16 The ductal obstruction that can occur with a stone or with strictures involving the ampulla of Vater or the duct of Wirsung can clearly lead to injury as I've already described.

03:27 The pancreas, the exocrine pancreas is a bag of digestive juices and if you get injury to that exocrine pancreas, those digestive juices, lipases, and proteases and other digestive enzymes can start breaking down the pancreas itself.

03:49 So, alcohol by mechanisms that involve slowing the flow of the pancreatic digestive enzymes down the pancreatic duct or by causing direct acinar pancreatic epithelial cell injury.

04:04 Certain drugs, ischemia, a number of agents can cause direct exocrine pancreas damage which will release those enzymes and cause then the ongoing inflammation.

04:19 Some drugs and alcohol is also part of this can cause an aberrant targeting of the intracellular enzymes which are zymogens within a secretory vesicle may target them to the lysosome.

04:37 When that happens that targeting allows those enzymes to be activated inappropriately intracellularly leading them to damage to that cell, release of the enzymes, damage to adjacent cells and we’re off and running.

04:51 Basically, what we're doing is turning loose all of the pancreatic enzymes and they're autodigesting the pancreas. This will lead to parenchymal destruction.

05:01 You will get hemorrhage because you're damaging blood vessels, you will also get a very profound fat necrosis because of the lipases that are present.

05:11 The clinical presentation of pancreatitis when it's acute onset it is severe abdominal pain, it increases progressively with severity as you progress to digest your pancreas, it starts epigastric but will eventually radiate to the back.

05:26 Because of the severe inflammation, you will get nausea and vomiting, you won't feel like eating, there may be increased bowel motility so you'll have diarrhea.

05:36 You're also going to get diarrhea because you're not releasing the normal digestive enzymes into the duodenum and into the small bowel so you won't get normal breakdown and absorption of the various nutrients and so you'll get a secretory diarrhea pulling water in plus the bowel bacteria will have a field day with all those undigested metabolites.

05:59 It's an inflammation so there will be a low-grade fever and clearly there is abdominal pain.

06:06 There are a couple warning signs for impending disaster with indicating that there is severe and widely necrotizing pancreatitis.

06:15 So, digestion not only in the pancreas but surrounding fat and potentially progressing into the bowel wall and also into the peritoneum.

06:26 So a peri-umbilical hemorrhage is called a Cullen sign and hemorrhage on the flanks is called Grey Turner sign.

06:33 And these are indications that we have a severe necrotizing pancreatitis.

06:40 Making the diagnosis, it's the clinical picture, it's how the patient presents.

06:44 The laboratory studies that we would do is looking for elevated amylase or lipase indicating that we have had damage to the pancreatic parenchyma.

06:51 You may see that there is an elevated transaminase or elevated bilirubin that suggests gallstones, may be the primary etiology.

07:00 If hypercalcemia, driving the abnormal release of the pancreatic enzymes is the cause then you may see elevated levels of calcium.

07:10 In certain forms of autoimmune pancreatitis, there may be elevated levels of immunoglobulin G4, IgG4-related disease.

07:17 And the characteristic findings are going to be much more on imaging overall.

07:22 So you will see edematous parenchyma within the pancreas with associated edema and hemorrhage.

07:33 Interesting that for roughly 30% of cases of pancreatitis where it's relatively localized, the imaging, computerized tomography or ultrasound or MRI, may be normal.

07:47 But we're looking for edema, we're looking for bleeding. We may be identifying gallstones.

07:54 The pancreatic or common bile duct may be dilated.

07:58 We'll see fluid collections, necrosis, the formation of pseudocysts, and because of the fat necrosis we may also see calcifications.

08:06 How are we going to manage these? Well, this is actually a pretty bad disease, you don't mess around with the pancreas.

08:11 You don't want to have the pancreas secreting any more than it needs to, we put the bowel at complete rest so there is nothing by mouth.

08:19 We may do nasogastric suction to keep any gastric fluid from going more distally.

08:25 Because the injury with release of lipases and proteases systemically can cause extreme vasodilation and loss of normal vascular tone, we're going to have to give aggressive intravenous fluid resuscitation.

08:39 There's going to be abnormal electrolyte imbalances. As we're having fat necrosis, we're sucking up a variety of electrolytes.

08:46 We want to give pain medication, we want to give things that damp down emesis, and we want to treat the underlying cause.

08:54 So if it's alcohol, take away the alcohol. If it's a stone, we want to get rid of the stone. You get the idea.

09:01 So the various complications that can occur because of pancreatitis.

09:05 With large areas of pancreatic necrosis, those may become infected and develop into frank abscess.

09:12 Where there is necrosis that may be walled off over time, the necrotic debris may be cleaned up and you develop a pseudo cyst.

09:18 With profound intraabdominal edema, you can get an abdominal compartment syndrome where you increase the peritoneal pressure so much that you compromise vascular flow.

09:33 The elaboration of a variety of the proteases may cause venous thrombosis so you may end up with an IVC thrombosis.

09:43 And then because of the release of lipases and other exocrine pancreatic enzymes into the circulation, you may actually affect other tissues in the body besides the peritoneum and that is to say the lungs.

09:56 And lipases in the lungs can actually break down a lot of the basement membrane and the cellular architecture as well as the normal surfactant and so you can end up with acute respiratory distress syndrome caused by pancreatitis.

10:12 The mortality overall from pancreatitis is 5% so this is not a disease that you mess around with.

10:20 With that, we have covered pancreatitis.