Pancreatitis: Pathology review

Definitions & Key takeaways

Pancreatitis refers to inflammation of the pancreas, an organ located behind the stomach that produces hormones and enzymes that help the body digest food. Pancreatitis can be acute or chronic.

Acute pancreatitis occurs when there is a sudden and severe inflammation, which usually resolves within a few days with proper treatment. It is commonly caused by gallstones and alcohol, and typically presents with epigastric pain that radiates to the back, nausea, vomiting, and decreased bowel sounds.

Chronic pancreatitis occurs when there is a long-term inflammation that can cause permanent damage to the pancreas and lead to serious complications. It is usually due to long-term alcohol use, genetic diseases like SPINK1 mutations and cystic fibrosis, pancreatic duct obstruction due to tumors, and autoimmune conditions.

People with chronic pancreatitis may be initially asymptomatic for a long time, but they might develop epigastric pain that radiates to the back, steatorrhea, fat-soluble vitamin deficiency like vitamin A, D, or E; diabetes, and unintentional weight loss.

Chapters:

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Case Study0:00–1:07

While in the Emergency Department, two individuals came in with severe epigastric pain. Michael who is 45, complains of pain that radiates to his back, vomiting, and nausea.
All of these symptoms appeared after he came home from partying at the bar a few hours ago. On the clinical examination, there’s epigastric tenderness without guarding or rebound, decreased bowel sounds, and purple discoloration around the periumbilical region.
He also tends to bend over to relieve the pain. Anna, who is 29 years old, on the other hand, says the pain started abruptly and that it doesn’t radiate anywhere.
She also noticed it gets worse after her meals. On examination, she presents with epigastric pain, scleral icterus, and fever.
Both were admitted and started on IV fluids. Blood tests were ordered, which revealed lipase and amylase levels that were 3 times more than normal.
Ok, so from what we can gather, both people have acute pancreatitis. Let’s begin with a bit of physiology.

Physiology1:07–2:43

The pancreas is located in the epigastric region, behind the stomach, and it is mostly a retroperitoneal organ. It has both endocrine functions, by releasing hormones like insulin and glucagon, and exocrine functions by secreting enzymes needed for food digestion.
The exocrine pancreas releases digestive enzymes through smaller ducts which drain in the main pancreatic duct. The main pancreatic duct, which travels through the length of the pancreas, joins the common bile duct at the ampulla of Vater and drains into the duodenum.
Now, the main pancreatic enzymes include pancreatic amylase which breaks down carbohydrates; trypsin and chymotrypsin, which break down proteins; and lipase which breaks down lipids.
To protect the pancreas from destroying itself, the acinar cells of the pancreas manufacture zymogen, or the inactive form, of trypsin, called trypsinogen.
When this zymogen is released into the small intestine, it is cleaved by enteropeptidase enzymes found in the duodenum. If, by any chance, trypsinogen gets auto activated before it reaches the duodenal lumen, trypsin gets cleaved and inactivated by trypsin itself or inhibited by certain proteins, called trypsin inhibitors, like SPINK1; In contrast, pancreatic lipase and amylase are secreted in their active forms and don’t need activation by the protease trypsin.
Ok, so pancreatitis is an inflammation of the pancreas. In acute pancreatitis, trypsin and chymotrypsin get suddenly get activated within the pancreas and cause autodigestion, which results in inflammation and hemorrhaging.

Acute Pancreatitis2:43–6:23

Once the pancreatic cells get damaged, increased amounts of lipase enter the blood, which is why these two enzymes are measured to diagnose pancreatitis.
For your test, it’s important to know that lipase, released by the damaged cells, breaks down triglycerides in free fatty acids which bind calcium.
So this kind of damage is also called saponification necrosis because the resulting tissue resembles soap. In chronic pancreatitis, there are persistent causes of inflammation in the pancreas, leading to impairment of both endocrine and exocrine functions.
Okay, let’s look at some of the causes for pancreatitis. Starting with acute pancreatitis which is most commonly caused by gallstones, followed by alcohol use.
On your test, you can remember the full list of causes by using the mnemonic “I GET SMASHED. ”‘I’ refers to Idiopathic causes.
‘G’ is obstruction by Gallstones, which get stuck in the bile duct and prevent pancreatic enzymes from reaching the small intestine.
This causes the digestive enzymes to back up into the pancrase where they build up and damage the organ. ‘E’ is Ethanol, or alcohol use, and it is not sure how it leads to pancreatitis.
‘T’ is a pancreatic Trauma, mostly puncture injury, like a knife wound, which damages the pancreas and releases the digestive enzymes.
‘S’ is the use of Steroids, which leads to increased viscosity of pancreatic secretions, causing obstruction of the small pancreatic ducts.
‘M’ is infection with Mumps virus, and it is believed to directly damage the pancreatic acinar cells. ‘A’ is the result of Autoimmune diseases, like systemic lupus erythematosus and rheumatoid arthritis.
These diseases are caused by auto-antibodies that target various organs in the body, such as the pancreas, and cause inflammation.
The second ‘S’ is the result of a Scorpion sting, which also damages the pancreas directly. ‘H’ is a cheat and stands for both Hypertriglyceridemia and for Hypercalcemia.
When taking a test, remember that hypertriglyceridemia above 1000 milligrams per deciliter can cause pancreatitis because it increases the concentrations of chylomicrons in the blood.
Chylomicrons are very large and obstruct capillaries leading to ischemia of the pancreas. A helpful hint for your test is that this type of pancreatitis improves with fasting.
In hypercalcemia, calcium molecules deposit in the pancreatic tissue, and activate trypsinogen, leading to pancreatic injury.
‘E’ is trauma from an Endoscopic retrograde cholangiopancreatography or ERCP which is a technique used to diagnose and treat various biliary and pancreatic diseases.
And finally ‘D’ stands for Drugs, like didanosine, Corticosteroids, Alcohol, Valproic acid, Azathioprine, and Diuretics like Furosemide and Bumetanide, which, for your tests, can be remembered using the mnemonic Drugs Causing A Violent Abdominal Distress.
Okay, now let’s move on to chronic pancreatitis. Many causes for acute pancreatitis also cause chronic pancreatitis.

Chronic Pancreatitis6:23–7:12

These include idiopathic causes, gallstones, long-term alcohol use, autoimmune conditions, hypertriglyceridemia and hypercalcemia.
More chronic diseases or diseases that develop slowly usually cause damage that builds up over time in the pancreas. These include slow growing tumor that blocks the pancreatic ducts or genetic conditions like SPINK1 mutations that interfere with its protective action and cystic fibrosis where a mutation in the CFTR gene causes the production of abnormal trypsins that activate prematurely in the pancreas.

Symptoms7:12–8:47

Ok so symptom-wise, you need to remember that pancreatitis usually results in epigastric pain that radiates to the back - which improves when the individual bends forward, along with nausea and vomiting over several hours.
More severe cases might present with decreased bowel sounds, and hypovolemic shock due to sequestration of fluid into a third-space - which is a fancy word for liquid outside the blood vessels that isn’t supposed to be there.
Sometimes, on your test, the only clue for pancreatitis is the Cullen sign which is an ecchymotic or purple discoloration in the periumbilical region or the Grey Turner sign where the ecchymotic discoloration is along the flank.
Both of these signs suggest retroperitoneal bleeding due to pancreatic necrosis. Chronic pancreatitis may be asymptomatic for a long time, but at some point, it can begin to cause symptoms like epigastric abdominal pain that radiates to the back.
It can also cause symptoms of both pancreatic exocrine and endocrine insufficiency. Remember in pancreatic insufficiency the pancreas doesn’t produce enough insulin and digestive enzymes, unlike in acute pancreatitis where there’s a sudden abundance of digestive enzymes.
The result of pancreatic insufficiency is fat malabsorption, which leads to steatorrhea, fat-soluble vitamin deficiency like vitamin A, D or E; diabetes; and unintentional weight loss.
Next, diagnosis is confirmed by a set of lab work. In acute pancreatitis, the serum lipase and serum amylase both rise to at least 3 times the upper limit of normal - usually above 200 units per liter.

Diagnosis8:47–10:57

Complete blood count may show leukocytosis or an elevated hematocrit due to dehydration or acute hemorrhaging. The C-reactive protein and lactate dehydrogenase are usually elevated due to inflammation.
Ionized calcium levels can be low if there’s fat necrosis, which binds calcium. Next, on abdominal ultrasound, the pancreas will be enlarged and hypoechoic.
Ultrasound can also diagnose gallstones, by showing stone formation in the gallbladder. If the diagnosis of acute pancreatitis is still unclear, then an abdominal CT with contrast can be done, usually showing pancreatic necrosis, inflammation, and retroperitoneal fluid.
Ultimately, what you need to remember is that diagnosis is made when the individual presents at least 2 out of the 3 criteria: acute epigastric pain often radiating to the back, serum amylase or lipase levels 3 times higher upper limit of normal, and characteristic imaging findings.
Lab work for chronic pancreatitis also include labs like serum lipase and amylase, CBC, and electrolytes. However all of these are usually normal.
In some cases, bilirubin and alkaline phosphatase can be elevated, suggesting that something is compressing the bile duct, like a tumor.
Next, remember that a 72-hour stool collection is done because that’s the gold standard for diagnosing fat malabsorption.
A transabdominal ultrasound and a CT scan can be done and both will show calcifications in the pancreas which is the classic sign for chronic pancreatitis on your exams!.
In addition, there may be ductal dilation, enlargement of the pancreas, and fluid collections around the pancreas. Treatment of acute pancreatitis starts with fluid resuscitation, which is done using isotonic crystalloid solutions, like saline or lactated Ringer solution.

Treatment 10:57–11:51

Pain control is done with IV opioids, such as Hydromorphone or Fentanyl. Individuals should also not take anything by mouth, and it’s always important to address the underlying cause of pancreatitis.
Treatment of chronic pancreatitis is mainly dietary modifications like not drinking alcohol, drinking at least 1.5 liters of water each day, and eating small low-fat meals.
In some cases, an individual may also be given exogenous pancreatic enzymes to give the pancreas a break from enzyme secretion.
This tends to decrease intraductal build up of enzymes and improve pancreatic ischemia. Okay, time for a review!
Pancreatitis refers to inflammation of the pancreas. Acute pancreatitis is mostly caused by gallstones and alcohol, among many other things that can be remembered using the mnemonic ‘I GET SMASHED.’ Common symptoms include epigastric pain that radiates to the back, nausea, vomiting, decreased bowel sounds, and the Cullen sign or the Grey Turner sign.

Review11:51–13:31

A diagnosis is made when at least 2 out of the 3 criteria are present: acute epigastric pain often radiating to the back, serum amylase or lipase levels 3 times higher upper limit of normal, or characteristic imaging findings like enlarged pancreas or areas of necrosis.
Chronic pancreatitis is usually due to more chronic causes of inflammation such as long term alcohol use, genetic diseases like SPINK1 mutations and cystic fibrosis, pancreatic duct obstruction due to tumors, and autoimmune conditions.
Individuals may be initially asymptomatic for a long time, but they might develop epigastric pain that radiates to the back, steatorrhea, fat-soluble vitamin deficiency like vitamin A, D or E; diabetes, and unintentional weight loss.
Lab work for chronic pancreatitis can include serum lipase and amylase, and CBC but all of them are usually normal. Additionally, a 72 hour stool collection is done to diagnose fat malabsorption.
And finally, transabdominal ultrasound and a CT scan can be done which will show calcifications in the pancreas. Back to our cases.
Michael came in with severe abdominal pain that radiates to his back, decreased bowel sounds, and ecchymosis around the periumbilical region, which is the classic Cullen sign.

Summary13:31–14:20

Blood tests showed increased lipase and amylase levels, so he most likely has acute pancreatitis, probably due to alcohol consumption.
If an abdominal CT were to be taken, it would show pancreatic necrosis and diffuse enlargement. Anna came in with localized abdominal pain, and her scleras were jaundiced.
This, alongside high levels of lipase and amylase levels, makes us think she might also have acute pancreatitis but this time due to gallstones.
ERCP would confirm the diagnosis. But remember!
ERCP is also a cause of acute pancreatitis!
Pancreatitis: Pathology Review: Video and Causes | Osmosis