Chronic pancreatitis: Clinical sciences

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Introduction0:00–1:00

Chronic pancreatitis refers to persistent chronic inflammation of the pancreas that's associated with irreversible changes such as fibrosis, calcifications, and atrophy.
This eventually decreases the function of the exocrine pancreas, subsequently causing difficulties with digestion and absorption of nutrients, as well as abdominal pain that's worse with eating, steadorrhea, and unintentional weight loss.
Additionally, the destruction of the endocrine pancreas can lead to difficulties in producing hormones such as insulin. Now, there's a variety of conditions that can cause chronic pancreatitis, including toxins like chronic alcohol consumption and metabolic conditions.
Genetic and autoimmune conditions as well as recurrent acute pancreatitis and ductal obstruction. An important thing to remember is that tobacco smoking may not be a direct cause, but it is a strong risk factor.
Now, if you suspect chronic pancreatitis, first perform an ABCDE assessment to determine if your patient is unstable or stable.

Unstable patient1:00–1:26

If unstable, stabilize the patient's airway, breathing, and circulation. Next, obtain IV access and if needed, start IV fluids.
Finally, put your patient on continuous vital sign monitoring. OK, now, let's go back to the ABCDE assessment and take a look at stable individuals.

Stable patient1:26–2:26

If the patient is stable, obtain a focused history and physical examination. These patients typically report upper abdominal pain that can range from constant and dull, to acute and stabbing.
Sometimes the pain might radiate to the back and can be relieved by leaning forward. Other important history findings include nausea, vomiting, and diarrhea.
Also, they might report fatty stools that are difficult to flush, abdominal bloating, and unexplained weight loss. Moreover, these findings typically occur due to progressive loss of assiner cells that eventually result in decreased production of digestive enzymes and subsequent malabsorption.
This condition is called pancreatic exocrine insufficiency, or PEI for short. On the other hand, physical exam findings typically include tenderness to palpation in the upper abdomen.
At this point, you should suspect chronic pancreatitis. Your next step is to order labs, such as lipase, amylase, fecal elastase 1, trypsinogen, and trypsin.

Suspect chronic pancreatitis2:26–3:15

Additionally, don't forget to order imaging, primarily CT or MRI. But in some cases, you may also get an endoscopic ultrasonography or EUS as well as a secretin stimulated magnetic resonance cholangiopancreatography or SMRCP.
Rarely, you may want to get a biopsy of the pancreas. A clinical pearl to keep in mind is that there's no single diagnostic test for pancreatitis.
So, your diagnosis must be based on a combination of the right history, clinical presentation, lab results, and imaging findings.
Labs often reveal elevated amylase and lipase, as well as low fecal elastase 1, trypsinogen, and trypsin. Keep in mind that in acute pancreatitis, amylase and lipase would be elevated more than 3 times the upper limit of normal.

Labs & Imaging3:15–4:40

However, in chronic pancreatitis, these enzymes can be only mildly elevated or even normal, especially as the pancreas is replaced by increasing amounts of fibrotic tissue later in the disease process.
For this reason, they are a poor indicator of pancreatic inflammation and do not correlate with the severity of clinical presentation in chronic pancreatitis.
That's why you need imaging. CT or MRI typically reveals the chain of lakes sign from dilated and irregular pancreatic ducts, as well as extensive ductal calcifications, which are findings highly suggestive of chronic pancreatitis.
Additionally, there might be pancreatic atrophy, which is actually highly specific for end-stage chronic pancreatitis. If the CT or MRI is inconclusive, proceed with the US or SMRCP to get more detailed examination of pancreatic and ductal abnormalities.
If additional imaging is still not confirmatory for chronic pancreatitis, but your clinical suspicion remains high, consider a biopsy of the pancreas.

Chronic pancreatitis4:40–5:11

Now, the combination of the clinical presentation with these lab results and imaging findings, is highly suggestive of chronic pancreatitis.
Once you set the diagnosis, your next step is to determine the underlying cause. A pneumonic that can help you remember the most common causes of chronic pancreatitis is tigaro, which stands for toxic and metabolic, idiopathic, genetic, autoimmune, recurrent acute pancreatitis or RAP, and obstruction.

Toxic/Metabolic5:11–6:36

First, let's start with toxic and metabolic causes. For example, if your patient reports excessive alcohol use, you should suspect alcohol-induced pancreatitis, and order labs, primarily AST and ALT.
If AST and ALT are elevated, usually around 2 times the upper limit of normal, this supports the diagnosis of alcohol-induced pancreatitis.
On the flip side, history might reveal long-term use of certain medications that can lead to drug-induced pancreatitis, such as aminosalicylates, antibiotics like sulfonamides, or tetracyclines, immunosuppressive agents like cyclosporine and azathioprine, corticosteroids, antihypertensives like ACE inhibitors, diuretics like furosemide, and anti-diabetic medications like incretins.
If that's the case, think of drug-induced pancreatitis. Keep in mind that these are just examples, and that there are 100s of medications that can cause chronic pancreatitis, so carefully review your patient's medication list.
Finally, if your patient reports excessive thirst and urination, bone pain, and possible thiazide use, suspect hypercalcemia-related pancreatitis.
Next, order serum and ionized calcium levels, because elevated serum and ionized calcium levels are highly suggestive of hypercalcemia-related pancreatitis.

Genetic6:36–7:12

OK, now, let's move on to genetic causes. If you have a young patient with chronic pancreatitis of unclear etiology, frequent respiratory infections, and non-specific findings on physical exam, consider cystic fibrosis.
To confirm or rule out cystic fibrosis, order genetic testing to check for abnormalities in the cystic fibrosis Transmembrane conductance regulatory gene, or CFTR gene, for short.

Autoimmune7:12–8:01

If the test detects gene abnormalities, there's a high probability that the chronic pancreatitis is caused by cystic fibrosis.
Keep in mind, there are several other known genetic causes of pancreatitis, so you should consider referring patients for genetic testing, especially if they have a positive family history.
Now, let's move on to autoimmune causes. In these patients, there might be no abdominal pain, but their history could reveal other autoimmune conditions, such as ulcerative colitis, primary sclerosing cholangitis, or Sjogren's syndrome.
Additionally, physical exam might show jaundice. In this case, you should suspect autoimmune pancreatitis.

RAP8:01–8:25

So, your next step is to check serum immunoglobulin G4, serum bilirubin, as well as alkaline phosphatase. Serum immunoglobulin G4 could be elevated in some types of autoimmune pancreatitis, but serum bilirubin and alkaline phosphatase are elevated in most types of autoimmune pancreatitis.
All of these findings are highly suggestive of autoimmune chronic pancreatitis. Switching gears, patients with chronic pancreatitis most commonly present with recurrent acute pancreatitis, often referred to as rap.

Obstruction8:25–9:12

History will reveal multiple recurrent episodes of acute pancreatitis with complete resolution of inflammation between episodes.
The risk of progression is even higher if the patient is consuming alcohol or using tobacco. Finally, let's consider cases where there is a pancreatic ductal obstruction.
Some important causes to keep in mind include gallstones, pseudocysts, symptomatic strictures, and even malignancy, primarily pancreatic cancer.
In these individuals, history typically includes severe acute abdominal pain, while physical exam findings usually reveal jaundice and possibly a palpable mass at the pancreatic head.

Idiopathic9:12–9:56

At this point, you should suspect ductal obstruction, so don't forget to order labs, primarily serum bilirubin, and alkaline phosphatase, and get a CT or MRI.
Elevated serum bilirubin, elevated alkaline phosphatase, and imaging that shows an obstructive mass are highly suggestive of pancreatic duct obstruction.
Now, you might have noticed we haven't covered the eye intigaro. This is because idiopathic chronic pancreatitis is a diagnosis of exclusion, meaning you must rule out other possible causes before you can say it's idiopathic.

Management9:56–11:37

If your history, physical exam, and additional testing do not support another etiology for chronic pancreatitis, you can consider idiopathic pancreatitis.
Here's a high yield fact. Chronic pancreatitis can lead to important complications causing morbidity and mortality, including chronic debilitating pain, malnutrition, diabetes mellitus, pancreatic pseudocysts, pancreatic cancer, and even splenic vein thrombosis.
OK, now that we've addressed the most common underlying causes of chronic pancreatitis, let's turn our attention to management.
First, you need to address your patient's pain. The first line medications for pain relief are NSAIDs and acetaminophen, but depending on your patient's pain severity, you could escalate pain management to include tricyclic antidepressants or TCAs, selective serotonin reuptake inhibitors, or SSRIs, pregabalin, as well as antioxidant therapy or opiates.
If the pain is refractory, consider celiac plexus block. Next, assess the severity of symptoms associated with pancreatic exocrine insufficiency, and if needed, start pancreatic enzyme replacement therapy and optimize nutrition with small, frequent, and low fat meals.
Once you have optimized your patient, you have to treat the underlying cause. This may include encouraging lifestyle modification such as alcohol and tobacco secession.
Patients with autoimmune causes may require treatment with corticosteroids, while some patients with ductal obstructions may need endoscopic management.

Review11:37–14:11

Additionally, keep in mind that in chronic pancreatitis, inflammation of the tissue affects both endocrine and exocrine secretion, so it's important to regularly screen your patients for diabetes mellitus, as well as fat soluble vitamin deficiencies, including vitamins A, D, E, and K, and osteoporosis.
Lastly, when the pain is severe, refractory, and doesn't respond to all these measures, consider total pancreatectomy with eyelet auto-transplant.
All right, as a quick recap, if you suspect chronic pancreatitis, first perform the ABCDE assessment to determine if your patient is unstable or stable.
If unstable, proceed with acute management and stabilize them. On the flip side, if you suspect chronic pancreatitis in a stable individual, order labs and imaging.
Labs typically reveal elevated amylase and lipase, as well as low fecal elastase one, trypsinogen, and trypsin. Additionally, CT or MRI typically reveals the chain of lakes sign, extensive calcifications, and in severe cases, pancreatic atrophy.
If inconclusive, proceed with EUS or SMRCP. At this point, you can confirm the diagnosis of chronic pancreatitis, so you need to determine the cause.
A pneumonic that can help you remember the most common causes is Tgaro. T stands for toxic and metabolic, like alcohol induced, medication induced, and hypercalcemia related pancreatitis.
I stands for idiopathic, and G for genetic, like cystic fibrosis. Next up is A for autoimmune chronic pancreatitis, R for recurrent acute pancreatitis, and finally, O for ductal obstruction.
Once you determine the cause, proceed with management. Start by addressing the pain, and for patients with PEI, start pancreatic enzyme replacement therapy.
Then be sure to treat the underlying cause, which can include lifestyle modifications, corticosteroids, or even endoscopic management.
Schedule periodic screenings for diabetes mellitus, fat-soluble vitamin deficiencies, and osteoporosis. Lastly, patients whose pain remains severe or refractory to all these measures might be candidates for total pancreatectomy with eyelet