Chronic pancreatitis (CP) is irreversible injury to the pancreas caused by chronic inflammation and fibrosis. It commonly results from long-term heavy alcohol use or other causes like genetic mutations or obstruction of the pancreatic duct. CP leads to impairment of exocrine and endocrine pancreatic function over many years, resulting in abdominal pain, steatorrhea from fat maldigestion, diabetes, and nutritional deficiencies. Treatment focuses on pain management, pancreatic enzyme replacement, diabetes control, and nutritional support. Complications include pseudocysts, ascites, biliary or duodenal obstruction, and an increased risk of pancreatic cancer.

1. Chronic pancreatitis
Prepared & Presented by
Dr.Abdirazaq Ali Yusuf
(Dr.Cazaam),
Internalmedicinedepartment
@Somali National University

2. General
Chronic pancreatitis (CP) is defined as irreversible injury to the
pancreas caused by chronic inflammation and fibrosis leading to
impairment of the exocrine and endocrine functions of the pancreas.
The incidence of CP in the US is 3 – 10 cases per 100 000 persons, with
a prevalence of 27 – 35 per 100 000.

3. Alcohol:
The majority of cases of CP in western countries are caused by chronic alcoholism. The
median age of onset of CP is 36 years.
 Most patients have a history of drinking 150 g/day for at least 5 – 10 years (a standard
12 - ounce [350 mL] beer contains approximately 18 g of alcohol).
 Only 5 – 10% of heavy drinkers develop CP. Proposed cofactors that contribute to the
development of CP include genetic variations, including polymorphisms of proteins
involved in cellular antioxidant defense or alcohol metabolism, consumption of high –
protein and high - fat diets, hyperlipidemia, exposure to bacterial endotoxins, and
smoking.
 The strongest cofactor seems to be smoking. Ninety percent of patients with alcoholic
CP are smokers. Smoking is also an independent risk factor for the development of CP.
Smoking leads to the rapid development of pancreatic calcifications.
Etiology and Pathogenesis

4. The pathogenesis may follow a necrosis – fi brosis pathway, in which
repeated episodes of acute pancreatitis lead to irreversible fi brosis
and atrophy. This is also referred to as the SAPE (sentinel acute
pancreatitis event) hypothesis. Alcohol also causes zymogens to be
prematurely activated, leading to autodigestion of the pancreas.
Finally, alcohol use causes increased secretion of proteins and
ionized calcium from acinar cells with a relative decrease in bicarbonate
secretion. This leads to precipitation of proteins and obstruction
of ductules.

5. Idiopathic:
 10 – 30% of cases of CP are idiopathic. Contributing factors include
genetic abnormalities, modest alcohol consumption in susceptible patients,
surreptitious alcohol use, trauma, and smoking.
Obstruction:
 Chronic obstruction of the pancreatic duct can cause CP proximal to
the obstruction, and relief of the obstruction occasionally reverses
damage to the pancreas.
 Causes of obstruction include pancreatic, ductal, or ampullary
tumors, benign ductal strictures, and pancreatic divisum with stenosis
of the minor papilla.
 In eastern countries, bile duct disorders, such as gallstone disease,
are thought to be a major cause of CP.

6. Tropical pancreatitis:
 Tropical pancreatitis is the most common form of CP in southwest
India and other tropical areas including Africa, southeast Asia, and
Brazil.
 The etiology is unknown, but there is an association with mutations
in the serine protease inhibitor Kazal type 1 ( SPINK1 ) gene, which
encodes a trypsin inhibitor (see Chapter 18 ) and thereby leads to
trypsin activation within the pancreas. Environmental triggers may
include malnutrition, including defi ciencies in calories or micronutrients,
and infections.
 A striking feature of tropical pancreatitis is that diabetes mellitus is
an inevitable consequence, and > 90% of patients develop pancreatic
calcifi cations.

7. Hereditary pancreatitis:
 Hereditary CP is associated with mutation of the protease serine 1
(PRSS1 ) gene and is transmitted in an autosomal dominant manner
with a penetrance of 80%.
 The PRSS1 gene encodes trypsinogen, and mutations lead to
increased autoactivation of trypsin within the pancreas. This allows
increased activation of various zymogens to their active proteolytic
forms, leading in turn to autodigestion of the pancreas.
Other genetic factors:
 Other mutations may act as cofactors or increase susceptibility to or
the severity of CP. These include mutations in SPINK1 and the cystic
fi brosis transmembrane conductance regulator ( CFTR ) gene.
 Mutations of the CFTR gene that are not severe enough to cause
cystic fi brosis may predispose to CP.

8. Autoimmune pancreatitis:
 Autoimmune pancreatitis is a chronic inflammatory and fibrosing disease
of the pancreas.
 The characteristic feature of autoimmune pancreatitis is a dense
infiltration of the pancreas and other organs by plasma cells and
lymphocytes. The plasma cells secrete immunoglobulin G (IgG) or IgG4.
Metabolic disorders:
 Hypertriglyceridemia and hypercalcemia are associated with CP.
Up to 70% of cases of CP in Western countries are caused by alcohol;
however, only 5 – 10% of alcoholics develop chronic pancreatitis. A
convenient mnemonic for the causes of CP is TIGAR - O: toxic –
metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute
pancreatitis, or obstructive.

9. Clinical Features
Abdominal pain:
 Abdominal pain is the most common symptom of CP and contributes significantly to the
quality of life in patients with CP. The pain is typically epigastric and may radiate to the
back and sometimes around to the fl ank in a band - like manner. The pain is worse with
eating and may be associated with nausea and vomiting. Leaning forward relieves the pain
in some patients.
 Pain may be absent in some patients who present with pancreatic insufficiency.
Fatmaldigestion:
 Exocrine dysfunction typically occurs after acinar cell reserve is reduced by 90%. With
an inadequate lipase, fat maldigestion and steatorrhea occur. Patients may have loose, oily
stools with a foul odor.
 Osteopenia and osteoporosis are common due to malabsorption of
vitamin D. Deficiencies in other fat - soluble vitamins – A, E, and K
– and vitamin B12 may also occur.
Protein and carbohydrate defi ciencies may occur at later stages and to a lesser degree
than fat maldigestion.

10. Impaired glucose tolerance and diabetes mellitus:
 Impaired glucose tolerance resulting in diabetes mellitus results
from destruction of the islet cells and is similar to type I diabetes
mellitus; however, alpha cells are also destroyed, so patients lose the
ability to secrete glucagon, thereby making hypoglycemia more
common and more severe.
 Patients with CP who have a family history of diabetes mellitus are
more likely to develop diabetes mellitus.
Physical examination:
The only consistent finding on physical examination is epigastric
tenderness.
The differential diagnosis of CP includes peptic ulcer disease,
symptomatic gallstones, bile duct stricture, recurrent acute
pancreatitis, and pancreatic cancer.

11. Diagnosis
Imaging:
Imaging studies are frequently diagnostic in advanced disease.
Diagnosing early CP is diffi cult.
 Plain abdominal fi lms show calcifi cations in about 30% of patients
with CP. This fi nding, combined with loss of pancreatic function, can
be diagnostic of CP. Calcifi cations develop over 5 – 25 years and are
most common with alcoholic and tropical CP.
 Transabdominal ultrasonography and computed tomography (CT)
are useful. The sensitivity of ultrasonography is 50 – 80%, and the
specifi city is 80 – 90%. CT has a sensitivity of 75 – 90% and specifi city
of > 85% for the diagnosis of CP (see Chapter 27 ). Findings on CT
include calcifi cations, ductal stones, abnormal size of the pancreas,
a dilated pancreatic duct, and pseudocysts

12. Endoscopic retrograde cholangiopancreatography (ERCP) is
considered
the gold standard among imaging procedures for the diagnosis
of CP, with a sensitivity and specifi city of 70 – 90% and 80 – 100%,
respectively. ERCP reveals ductal abnormalities including stenoses,
dilatation (normal diameter of the main pancreatic duct is 3 mm),
and irregularities of the main pancreatic duct and its side branches.
A “ chain - of - lakes ” or “ beading ” appearance of the pancreatic duct,
indicating alternating areas of dilatation and stricture, is typical of
advanced CP. ERCP also facilitates therapeutic interventions, such as
placement of stents through stenoses or removal of ductal stones
from the pancreatic duct.

13. Magnetic resonance imaging (MRI) with
magnetic resonance
cholangiopancreatography (MRCP) is
noninvasive and has a sensitivity
and specificity comparable to that of ERCP.
 Endoscopic ultrasonography (EUS) is
highly sensitive for detecting
CP. Compared with ERCP, EUS has a lower
risk of complications and can detect
abnormalities suggestive of CP in the
pancreatic parenchyma and ductal system that
may not be not visible with other imaging
modalities

14. Tests of pancreatic function:
 Exocrine pancreatic insuffi ciency can be identifi ed directly by sampling
duodenal contents for pancreatic secretions after administering a
secretagogue such as secretin or cholecystokinin. Over a 1 - hour
intraduodenal collection, a bicarbonate concentration of < 80 mEq/L is
diagnostic of CP. This method is sensitive and can be useful in early CP, but
it is not widely available and requires passing a duodenal tube by mouth and
collecting pancreatic secretions for 1 hour.
Indirect measures of exocrine dysfunction include serum trypsinogen,
fecal chymotrypsin, and fecal elastase levels. Low levels indicate exocrine
insuffi ciency, but these tests are unreliable until CP is advanced. Of the
indirect tests, fecal elastase is widely available, requires only a single stool
sample, and may be the most sensitive
and specifi c of the fecal tests for diagnosing CP.

15. Other laboratory studies:
A 72 - hour stool fat quantitation in patients with CP is typically greater than 7 g/day.
A vitamin B12 absorption test (Schilling test) may help in the diagnosis of CP;
however, this test is not commonly used to diagnose CP and is generally not available.
 Serum amylase and lipase levels may be slightly elevated in patients
with symptomatic exacerbations of CP, but usually they are normal.
The diagnosis of CP depends largely on identifying characteristic clinical features
by history, often in the setting of chronic alcohol abuse. Diagnostic tests for CP may
be classified as those that detect abnormalities of pancreatic structure (imaging
tests) and those tests that detect abnormalities of pancreatic function. Traditionally,
ERCP has been considered the gold standard for assessing pancreatic ductal
structure, and the secretin stimulation test has been viewed as the gold standard for
assessing pancreatic function.

16. CP can cause a significant reduction in a patient ’ s quality of life,
and
treatment should focus on alleviating symptoms.
Patients should undergo imaging evaluation for the presence of
complicating
or concurrent factors, including pseudocysts, biliary stricture, or
pancreatic cancer.
General treatment recommendations include abstaining from alcohol
and smoking and eating small, frequent meals to limit pancreatic
enzyme secretion and to reduce symptoms of maldigestion.
Treatment

17. Medical treatment for pain includes:
acetaminophen or nonsteroidal anti - infl ammatory drugs (NSAIDS);
 uncoated pancreatic enzymes, which suppress the release of cholecystokinin,
the hormone that stimulates pancreatic secretion;
 narcotics, tricyclic antidepressant drugs, or gabapentin; however, narcotic addiction is a
major risk in patients with CP;
 antioxidants, which limit free - radical damage to the pancreas but are of uncertain benefit.
Surgical or endoscopic treatments include celiac plexus block, endoscopic
stenting of the pancreatic duct, pancreatic duct stone removal,
sphincterotomy, and surgical resection or decompression of the pancreatic
duct.

18. Maldigestion and steatorrhea:
Pancreatic enzyme replacement with enterically coated formulations that contain at least
40 000 U of lipase with each meal is recommended.
Non - enteric - coated pancreatic enzymes may be inactivated in the acidic environment
of the stomach; therefore, a proton pump inhibitor or histamine H2 receptor antagonist is
usually used in conjunction with such preparations.
Diabetes mellitus usually requires insulin in lower doses than those used for type I
diabetes mellitus. Insulin regimens should be tailored to reflect the increased risk of
hypoglycemia in patients with CP.
Patients may require nutritional support with vitamins A, D, E, and
K, as well as vitamin B12.
In the duodenum, vitamin B12 is bound to R - proteins. Vitamin B12 normally is
cleaved from R - proteins by proteases from the pancreas, thereby allowing the B12
to bind to intrinsic factor for absorption in the terminal ileum.
Pancreatic insufficiency may cause vitamin B12 deficiency by leading to reduced
cleavage of B12 from R - proteins.

20. Complications
Pseudocysts:
 Pseudocysts develop in 10 – 25% of patients with CP, most commonly
in those with alcoholic CP.
 Damage to pancreatic ducts leads to accumulation of pancreatic fluid
inside or outside of the pancreas.
 The pancreas and other adjacent structures, including the stomach,
transverse colon, and omentum, form the walls of the pseudoscyst;
 Many pseudocysts are asymptomatic, but as they increase in size,
abdominal pain is more likely;
 Other complications of pseudocysts may include obstruction of the
bile duct, duodenum, or adjacent blood vessels, formation of fistulas,
spontaneous infection, and abscess formation;

21. Enzymes in a pseudocyst may digest an adjacent arterial wall
to create a pseudoaneurysm; the splenic artery is the most
commonly affected vessel. A pseudoaneurysm may rupture, causing
bleeding into the pseudocyst, adjacent viscera, or the peritoneal
cavity. They may also bleed into the pancreatic duct, causing
hemosuccus pancreaticus, which may present as gastrointestinal
bleeding;
 Ultrasonography, CT, and MRI are used to diagnose pseudocysts;
 The indications for draining a pseudocyst include rapid enlargement,
persistent pain, compression of surrounding structures,
marked early satiety, and infection. Drainage may be achieved by a
percutaneous, endoscopic, or surgical approach.

22. Pancreatic ascites and pleural effusion:
 Disruption of the pancreatic duct or rupture of a pseudocyst can
lead to accumulation of pancreatic fl uid in the pleural or peritoneal
space;
Diagnostic paracentesis or thoracentesis will reveal fl uid with an
elevated amylase level, usually higher than 1000 U/L;
 Treatment includes withholding oral feeding to minimize
pancreatic secretions. Diuretics, serial paracentesis or thoracentesis,
and somatostatin analogs are also used. Many patients benefi t from
endoscopic placement of a stent across a disrupted pancreatic duct. In
some case surgical intervention is required.

23. Biliary or duodenal obstruction:
 Obstruction of the bile duct or the duodenum occurs at a rate of 10%
and 5%, respectively. Obstruction may be caused by a pseudocyst
or by fi brosis and infl ammation in the pancreatic head.
 Diagnostic studies include ERCP or MRCP for biliary obstruction
and CT, upper endoscopy, or an upper gastrointestinal series for
duodenal obstruction.
 Treatment may include drainage of an obstructing pseudocyst,
endoscopic stenting of a biliary or duodenal obstruction, or surgical
gastrojejunostomy or choledochoenterostomy for relief of duodenal
obstruction.

24. Splenic vein thrombosis:
 Pancreatic inflammation can cause thrombosis of the splenic vein,
which courses along the posterior aspect of the pancreas.
 Splenic vein thrombosis may lead to portal hypertension and isolated
gastric varices.
 Splenectomy is curative and is indicated if gastric variceal bleeding
occurs.
Pancreatic cancer:
Patients with CP are at an increased risk for developing pancreatic
cancer. The risk is about 4% after 20 years.

25. Prognosis
The quality of life of patients with CP is signifi cantly worse than that of the
general population. Tobacco use and ongoing alcohol use predict a worse
prognosis.
Abdominal pain often abates after 10 years or more of CP; frequently
this coincides with the development of pancreatic insufficiency. The
mortality ratio is approximately 3.6:1 when compared with patients
without CP. Continued alcohol use increases the mortality rate by another 60%.
The survival rate is about 70% at 10 years and 45% at 20 years. Most
patients die from an associated condition, such as complications from
continued alcohol use or smoking, or from pancreatic cancer or postoperative
complications.

26. Pearls
oThe diagnosis of chronic pancreatitis requires a high index of clinical suspicion
in a patient presenting with chronic abdominal pain.
Pain management is an important component of treatment of chronic pancreatitis.
oTobacco use and ongoing alcohol use predict a worse prognosis, and patients
should be encouraged to stop smoking and alcohol consumption.
DON’T FORGET

27. The End