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I GET SMASHED

Causes of Pancreatitis Mnemonic

Author: Georgina Tiarks

Editors: Alyssa Haag,Józia McGowan, DO

Illustrator: Jessica Reynolds, MS

Copyeditor: Sadia Zaman, MBBS, BSc

Modified: 1 Apr 2024

What is pancreatitis?

Pancreatitis is a medical condition describing inflammation of the pancreas. Pancreatitis can be either acute (i.e., sudden onset) or chronic (i.e., long term). Acute pancreatitis is typically caused by the over-activation of pancreatic enzymes, which can be due to either pancreatic acinar damage or outflow tract obstruction. The acinar cells of the pancreas are considered the functional cells that secrete enzymes; thus, in the case of their damage, enzyme secretion may be impacted. Similarly, if the pancreatic duct is obstructed, this can block the outflow of enzymes and cause accumulation within the pancreas. As a result, these pancreatic enzymes may proceed to destroy pancreatic tissue and autodigestion (i.e., digestion of tissue by an organ’s own enzymes) of parenchyma (i.e., functional organ tissue) may occur. The damage attracts inflammatory cells (e.g., neutrophils and macrophages) and cytokines (i.e., signaling molecules), resulting in pancreatic inflammation and acute pancreatitis. While chronic pancreatitis can occur secondary to acinar cell damage, outflow tract obstruction, or inappropriate enzyme activation, it occurs due to these acting progressively and over a longer period of time. 

What are the signs and symptoms of pancreatitis?

Periumbilical or epigastric pain that radiates to the lower abdomen, flank, chest, or back may indicate pancreatitis. Individuals may also experience nausea and vomiting. In some cases, Cullen sign (i.e., periumbilical bruising) or Grey-Turner sign (i.e., flank discoloration) may be present suggesting hemoperitoneum (i.e., internal bleeding). Blood work may show elevated serum amylase and lipase. Hypocalcemia (i.e., low calcium) and leukocytosis (i.e., high white blood cell count) may also be present. Sometimes elevated triglycerides can cause acute pancreatitis, in which case one may also find an associated hypertriglyceridemia.

What is I GET SMASHED?

I GET SMASHED is a mnemonic device used to help recall the causes of acute pancreatitis.

What does the “I” in I GET SMASHED mean?

The "I" stands for an idiopathic cause, which means that the cause is unknown. Between 15 to 25% of cases of pancreatitis are idiopathic.

What does the “G” in I GET SMASHED mean?

The "G" stands for gallstones, which are one of the most common causes of acute pancreatitis and may account for around 40% of pancreatic cases. Gallstones, also known as cholelithiasis, can be categorized as cholesterol stones, pigmented stones, or mixed stones. Cholesterol gallstones, the most common form, are a result of excess cholesterol. An imbalance between cholesterol, bile acids, and phospholipids causes cholesterol crystals to precipitate. Pigmented stones often occur in hemolytic states (i.e., red blood cell breakdown) causing excess unconjugated bilirubin. Comparatively, mixed stones may be due to infections in the biliary tract. 

What does the first “E” in I GET SMASHED mean?

The "E" stands for ethanol (i.e., alcohol). Heavy alcohol use may account for around one-third of acute cases of pancreatitis. Alongside gallstones, it is one of the most common causes of acute pancreatitis. Ethanol can also cause chronic pancreatitis. Several mechanisms have been linked to alcohol-induced pancreatitis including oxidative stress, pro-inflammatory mediators, uncoupling of oxidative phosphorylation (i.e., a metabolic pathway that is a main energy source for the body), and increased tissue necrosis.

What does the “T” in I GET SMASHED mean?

The "T" stands for trauma. Trauma from accidents or surgery may damage the pancreatic tissue and can thereby cause acute pancreatitis.

What does the first “S” in I GET SMASHED mean?

The "S" stands for steroid use. Large quantities of steroids can induce pancreatitis through an unknown mechanism within two weeks of exposure. Several mechanisms have been hypothesized, including changes to the viscosity of pancreatic secretions and modifications to lipid and calcium metabolism.

What does the “M” in I GET SMASHED mean?

The "M" stands for mumps, which is a viral infection. Studies have found that mumps is the most common cause of virus-induced pancreatitis. It can also cause parotitis (i.e., inflammation of the parotid gland), fatigue, fever, myalgia (i.e., muscle ache), and headache. 

What does the “A” in I GET SMASHED mean?

The "A" stands for autoimmune. Autoimmune pancreatitis occurs when the body’s immune system attacks the pancreas. Although the exact mechanism is unknown, it is associated with increased immune cell infiltration into pancreatic tissue and dysregulation of T-cells (i.e., lymphocytic immune cells). It may cause recurrent episodes of acute pancreatitis. Lab work may show an elevated IgG4 level in the case of autoimmune pancreatitis.

What does the second “S” in I GET SMASHED mean?

The "S" stands for scorpion poison. Although rare, scorpion stings may instigate acute pancreatitis among other systemic manifestations (e.g., numbness, dysphagia [i.e., difficulty swallowing], salivation, slurred speech, and breathing difficulties). One proposed mechanism is that the toxin induces cholinergic discharge (i.e., stimulates acetylcholine in the parasympathetic nervous system), which then promotes enzyme activation alongside widespread inflammation. Scorpion toxin-induced acute pancreatitis is usually self-limiting, but can become life-threatening on occasion.

What does the “H” in I GET SMASHED mean?

The "H" stands for both hypercalcemia and hypertriglyceridemia. Individuals with pancreatitis due to hypertriglyceridemia often have triglyceride levels above 1,000 mg/dL. There are two proposed mechanisms of hypertriglyceridemia-induced acute pancreatitis. The first suggests that elevated chylomicrons (i.e., lipoproteins carrying triglycerides) release free fatty acids (FFA) in the pancreas. These FFAs then create detergent structures that damage pancreatic tissue via acidosis, thereby activating trypsinogen (i.e., pancreatic enzyme). The second implies that elevated chylomicrons increase plasma viscosity leading to clogged capillaries. Again, acidosis may occur and subsequent activation of trypsinogen. Premature trypsinogen activation can then result in autodigestion of the pancreas via enzyme degradation of pancreatic tissue.

Similar to the proposed mechanism of hypertriglyceridemia, hypercalcemia above 14mg/dl is thought to occur due to premature activation of trypsinogen in response to calcium obstructing the pancreatic duct. The hypercalcemia may be due to a parathyroid disorder, multiple myeloma, or another chronic condition. However, hypercalcemia is typically a rare cause of pancreatitis.   

What does the second “E” in I GET SMASHED mean?

The "E" stands for endoscopic retrograde cholangiopancreatography (ERCP), which is a method used to diagnose conditions of the biliary or pancreatic ducts. ERCP can lead to acute pancreatitis through an obstruction, injury, allergy to contrast, or, in some cases, perforation during the procedure. These mechanisms ultimately lead to inflammatory over-activation post-ERCP.

What does the “D” in I GET SMASHED mean?

The "D" stands for drugs or medications. Medications such as immunosuppressants (e.g., azathioprine, mercaptopurine, leflunomide); chemotherapy (e.g., asparaginase); antimicrobials (e.g., pentamidine, didanosine, tetracyclines, dapsone, isoniazid, metronidazole, sulfonamides); anticonvulsants (e.g., valproic acid); hormone therapy (e.g., estrogen, tamoxifen); nonsteroidal anti-inflammatory medications (e.g., mesalamine, celecoxib, sulindac); blood pressure medications (e.g., thiazides, enalapril, methyldopa); cholesterol medications (e.g., simvastatin, fenofibrate); antiarrhythmic medications (e.g., procainamide); and diabetes medications (e.g., sitagliptin, exenatide) can all cause pancreatitis as a side effect.

What are the most important facts to know about the I GET SMASHED mnemonic?

The mnemonic I GET SMASHED represents common causes of acute pancreatitis. While gallstones and alcohol are among the most common causes of pancreatitis, other possible sources include idiopathic, trauma, steroids, mumps, autoimmune, scorpion stings, hypertriglyceridemia, hypercalcemia, endoscopic retrograde cholangiopancreatography, and drugs (i.e., medications) related sources. 

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