Pancreatitis: Pathology review

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A 58-year-old woman with a history of chronic alcohol use disorder comes to the office because of diarrhea, generalized weakness, and a 6.8-kg (15-lb) weight loss over the past 6 months. She reports intermittent dull upper abdominal pain that will last for days at a time and is not improved with antacids. After meals, she feels that her abdomen is distended. She characterizes her multiple daily bowel movements as greasy, foul-smelling, and oily. She recently was the driver involved in a minor traffic accident, which she attributes to worsening eyesight at night. Her temperature is 37.0°C (98.6°F), pulse is 78/min, respirations are 16/min, and blood pressure is 135/85 mmHg. Abdominal examination shows resonance to percussion throughout and a mildly tender epigastrium. Bowel sounds are hyperactive. Laboratory values show the following:  
 
 Laboratory value  Result 
 Calcium, serum  7.6 mg/dL 
 Partial thromboplastin time  60 seconds 
 Prothrombin time  28 seconds 

Which of the following is the most likely etiology of this patient's diarrhea?

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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. 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.

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.

These include idiopathic causes, gallstones, long-term alcohol use, autoimmune conditions, hypertriglyceridemia and hypercalcemia.

Summary

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.

Sources

  1. "Fundamentals of Pathology" H.A. Sattar (2017)
  2. "Robbins Basic Pathology" Elsevier (2017)
  3. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  4. "Chronic Pancreatitis: Challenges and Advances in Pathogenesis, Genetics, Diagnosis, and Therapy" Gastroenterology (2007)
  5. "Acute pancreatitis" The Lancet (2015)
  6. "The Epidemiology of Pancreatitis and Pancreatic Cancer" Gastroenterology (2013)
  7. "Laparostomy management using the ABThera™ open abdomen negative pressure therapy system in a grade IV open abdomen secondary to acute pancreatitis" International Wound Journal (2012)
  8. "Drug-Induced Acute Pancreatitis" Baylor University Medical Center Proceedings (2008)