Chronic Pancreatitis
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Chronic pancreatitis is a long-standing inflammation of the pancreas that alters the organ's normal structure and functions. It can present as episodes of acute
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
in a previously injured
pancreas The pancreas (plural pancreases, or pancreata) is an Organ (anatomy), organ of the Digestion, digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a ...
, or as chronic damage with persistent pain or
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
. It is a disease process characterized by irreversible damage to the pancreas as distinct from reversible changes in
acute pancreatitis Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes include a gallstone impacted in the common bile duct or the pancreatic duct, heavy alcohol use, systemic disease, trauma, elevated calcium levels, hypertriglyceridemia (w ...
. Tobacco smoke and alcohol misuse are two of the most frequently implicated causes, and the two risk factors are thought to have a synergistic effect with regards to the development of chronic pancreatitis. Chronic pancreatitis is a risk factor for the development of
pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...
.


Signs and symptoms

* Upper abdominal pain: Upper abdominal pain which increases after drinking or eating, lessens when fasting or sitting and leaning forward. Some people may not suffer pain. * Nausea and vomiting *
Steatorrhea Steatorrhea (or steatorrhoea) is the presence of excess fat in Human feces, feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incon ...
: Frequent, oily, foul-smelling bowel movements. Damage to the pancreas can reduce the production of pancreatic enzymes that aid digestion, causing
exocrine pancreatic insufficiency Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwach ...
. Fats and nutrients are not absorbed properly, leading to loose, greasy stool. It can also lead to malnutrition. * Weight loss even when eating habits and amounts are normal. * Type 3c diabetes (pancreatogenic diabetes): Chronic pancreatitis can affect the ability of the
pancreatic islet The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% o ...
s to produce
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...
to regulate
glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...
levels, leading to diabetes type 3c. Symptoms of diabetes type 3c are due to elevated sugar and may include increased hunger and thirst, frequent urination, weight loss, fatigue, and blurry vision. *
Osteopathy Osteopathy is a pseudoscientific system of alternative medicine that emphasizes physical manipulation of the body's muscle tissue and bones. In most countries, practitioners of osteopathy are not medically trained and are referred to as osteo ...
: Chronic pancreatitis is associated with an increased risk of osteopathy, including
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk. It is the most common reason f ...
and
osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop o ...
. Malnutrition, inflammation, and lifestyle factors contribute to the high prevalence of bone disorders in chronic pancreatitis patients. There have been three pain symptom profiles described in those with chronic pancreatitis. Type A involves intermittent, severe symptom flare-ups with or without objective pancreatitis, separated by pain-free periods. The type A symptom profile is usually more common early in the course of chronic pancreatitis. Type B chronic pancreatitis involves chronic pain accompanied by intermittent severe attacks. The type C symptom profile of chronic pancreatitis involves chronic, long-term, severe pain without interspersed acute flare-ups or symptom exacerbations.


Causes

Among the causes of chronic pancreatitis are the following: Chronic alcohol misuse and
smoking Smoking is a practice in which a substance is combusted, and the resulting smoke is typically inhaled to be tasted and absorbed into the bloodstream of a person. Most commonly, the substance used is the dried leaves of the tobacco plant, whi ...
are well-established risk factors for the development of chronic pancreatitis, and the two are thought to have a synergistic effect with regard to disease development. Alcohol use is present in 42–77% of those who have chronic pancreatitis, and tobacco use is present in greater than 60% of those with chronic pancreatitis. Genetic mutations are thought to be responsible for 10% of cases. This includes mutations of the
cystic fibrosis transmembrane conductance regulator Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the ''CFTR'' gene in 1989 as the gene lin ...
(CFTR), serine protease inhibitor Kazal-type 1 (SPINK1), and the chymotrypsin C (CTRC) proteins. 28% of cases of chronic pancreatitis are
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...
(of an unknown cause). In a small group of patients, chronic pancreatitis has been shown to be hereditary. Hereditary pancreatitis, which causes 1% of chronic pancreatitis, involves a mutation of the trypsin-1 gene that is inherited in an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
fashion. Almost all patients with
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
have established chronic pancreatitis, usually from birth. Cystic fibrosis
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
mutations have also been identified in patients with chronic pancreatitis but in whom there were no other manifestations of cystic fibrosis. Obstruction of the pancreatic duct because of either a benign or malignant process may result in chronic pancreatitis.


Pathophysiology

The mechanism of chronic pancreatitis viewed from a genetic standpoint indicates early onset of severe epigastric pain beginning in childhood. It is an
autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...
disease; chronic pancreatitis disease is identified in the cationic trypsinogen gene PRSS1, and mutation, R122H. R122H is the most common mutation for hereditary chronic pancreatitis with replacement of
arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...
with
histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an Amine, α-amino group (which is in the protonated –NH3+ form under Physiological condition, biological conditions), a carboxylic ...
at amino acid position 122 of the trypsinogen protein. There are, of course, other mechanisms – alcohol,
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is a deficiency, excess, or imbalance of energy, protein and other nutrients which adversely affects the body's tissues a ...
, smoking – each exhibiting its own effect on the pancreas.


Diagnosis

The diagnosis of chronic pancreatitis is made based on the history and characteristics of symptoms combined with findings on radiologic imaging. Serum
amylase An amylase () is an enzyme that catalysis, catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large ...
and
lipase In biochemistry, lipase ( ) refers to a class of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; howe ...
may be moderately elevated in cases of chronic pancreatitis. Symptoms of
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
, with oily, bulky, and foul-smelling stools indicated
steatorrhea Steatorrhea (or steatorrhoea) is the presence of excess fat in Human feces, feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incon ...
or fat malabsorption due to
exocrine pancreatic insufficiency Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwach ...
. Exocrine pancreatic insufficiency can be confirmed by also checking a fecal elastase level, with low levels specifying exocrine pancreatic insufficiency. A quantitative fecal fat test can also be done to quantify the fat levels in the stool and confirm the presence of exocrine pancreatic insufficiency. When chronic pancreatitis is caused by genetic factors, elevations in ESR, IgG4, rheumatoid factor, ANA and anti-smooth muscle antibody may be detected.
Computed tomography A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
, magnetic resonance cholangiopancreatography (MRCP), and endoscopic ultrasound (EUS) all have similar sensitivity and specificity for diagnosing chronic pancreatitis. MRCP is particularly utilized for its sensitivity in imaging the pancreatic ducts and bile ducts for associated changes such as
stones In geology, rock (or stone) is any naturally occurring solid mass or aggregate of minerals or mineraloid matter. It is categorized by the minerals included, its Chemical compound, chemical composition, and the way in which it is formed. Rocks ...
or strictures. A biopsy of the pancreas is not required for the diagnosis. On imaging, pancreatic and bile duct dilatation, atrophy of the pancreas, multiple calcifications of the pancreas, and enlargement of pancreatic glands can be found. On MRI scan, there is a low T1 signal due to inflammation, fibrosis, focal lesions, and calcifications. In those who are given a
contrast agent A contrast agent (or contrast medium) is a substance used to increase the contrast of structures or fluids within the body in medical imaging. Contrast agents absorb or alter external electromagnetism or ultrasound, which is different from radiop ...
, there would be a higher T1 signal with late gadolinium enhancement due to compression from the fibrotic areas. The overall thickness of the pancreas will be reduced.


Treatment

The different treatment options for the management of chronic pancreatitis are medical measures, therapeutic endoscopy, and surgery. Treatment is directed, when possible, to the underlying cause, and to relieve pain and malabsorption.
Insulin-dependent diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone require ...
may occur and need long-term insulin therapy. The abdominal pain can be very severe and require high doses of
analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...
s, sometimes including
opiate An opiate is an alkaloid substance derived from opium (or poppy straw). It differs from the similar term ''opioid'' in that the latter is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain ( ...
s. Medications such as
pregabalin Pregabalin, sold under the brand name Lyrica among others, is an anticonvulsant, analgesic, and anxiolytic amino acid medication used to treat epilepsy, neuropathic pain, fibromyalgia, restless legs syndrome, opioid withdrawal, generalized anx ...
,
gabapentin Gabapentin, sold under the brand name Neurontin among others, is an anticonvulsant medication primarily used to treat neuropathic pain and also for partial seizures of epilepsy. It is a commonly used medication for the treatment of neuropath ...
,
tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...
and serotonin–norepinephrine reuptake inhibitors (SNRIs) are commonly used to treat pain in chronic pancreatitis. Alcohol cessation is important to manage pain and slow the calcific process, possibly reducing the future risk of flare-ups.
Antioxidants Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...
may help, but it is unclear if the benefits are meaningful. Endoscopic treatments, including removal of stones in the pancreatic duct, and dilation of strictures may be done.
Extracorporeal shockwave lithotripsy Extracorporeal shockwave therapy (ESWT) is a treatment using powerful acoustic pulses which is mostly used to treat kidney stones and in physical therapy and orthopedics. Medical uses The most common use of extracorporeal shockwave therapy ...
can also be done, in which external acoustic waves are administered to break the stones. This may be combined with
endoscopic retrograde cholangiopancreatography Endoscopic retrograde cholangiopancreatography (ERCP) is a technique that combines the use of endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior ...
to collect larger stones. Behavioral treatments such as
cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...
including resilience training,
stress management Stress management consists of a wide spectrum of techniques and psychotherapy, psychotherapies aimed at controlling a person's level of psychological stress, especially chronic stress, generally for the purpose of improving the function of everyda ...
,
chronic pain Chronic pain is pain that persists or recurs for longer than 3 months.https://icd.who.int/browse/2025-01/mms/en#1581976053 It is also known as gradual burning pain, electrical pain, throbbing pain, and nauseating pain. This type of pain is in cont ...
rehabilitation programs and addiction treatment may also be used as adjunct treatments.


Pancreatic enzymes

Pancreatic enzyme replacement is often effective in treating the malabsorption and
steatorrhea Steatorrhea (or steatorrhoea) is the presence of excess fat in Human feces, feces. Stools may be bulky and difficult to flush, have a pale and oily appearance, and can be especially foul-smelling. An oily anal leakage or some level of fecal incon ...
associated with chronic pancreatitis. Treatment of CP consists of the administration of a solution of pancreatic enzymes with meals. Some patients do have pain reduction with enzyme replacement, and since they are relatively safe, giving enzyme replacement to a chronic pancreatitis patient is an acceptable step in treatment for most patients. Treatment may be more likely to be successful in those without the involvement of large ducts and those with idiopathic pancreatitis.


Surgery

Surgery to treat chronic pancreatitis tends to be divided into two areas – resectional and drainage procedures. Among the reasons to opt for surgery is if there is a pseudocyst,
fistula In anatomy, a fistula (: fistulas or fistulae ; from Latin ''fistula'', "tube, pipe") is an abnormal connection (i.e. tube) joining two hollow spaces (technically, two epithelialized surfaces), such as blood vessels, intestines, or other h ...
,
ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
, or a fixed obstruction. The Puestow procedure (anastomosis of the pancreatic duct to the jejunum to allow drainage of the obstructed duct), pancreaticoduodenectomy (partial pancreatic resection), or total pancreatectomy with or without autologous islet cell transplantation (removal of the whole pancreas, which is usually reserved for cases refractory to other surgical and medical interventions) may be used for treatment of chronic pancreatitis.


Epidemiology

The annual incidence of chronic pancreatitis is 5 to 12 per 100,000 persons. The prevalence of chronic pancreatitis in the U.S. is 90-100 per 100,000 adults. Chronic pancreatitis affects people in countries around the world.


See also

*
Exocrine pancreatic insufficiency Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack or reduction of digestive enzymes made by the pancreas. EPI can occur in humans and is prevalent in many conditions such as cystic fibrosis, Shwach ...
* Type 3c diabetes *
Acute pancreatitis Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes include a gallstone impacted in the common bile duct or the pancreatic duct, heavy alcohol use, systemic disease, trauma, elevated calcium levels, hypertriglyceridemia (w ...


References


Further reading

* *


External links


Mission: Cure

National Pancreas Foundation

Rebecca's Wish (pediatric pancreatitis)
{{Authority control Medical emergencies Pancreas disorders de:Pankreatitis#Chronische Pankreatitis