Cannabinoids and Pancreatitis

Pancreatitis- inflammation of the pancreas.  The pancreas is a gland located behind the stomach.  It releases the hormones insulin and glucagon, as well as digestive enzymes that help you digest and absorb food.

Causes

I         Acute pancreatitis
II        Chronic pancreatitis
III        Pancreatic abscess
IV        Pancreatic pseudocyst
Symptoms may include:

Abdominal pain
Chills
Clammy skin
Fatty stools
Fever
Mild jaundice
Nausea
Sweating
Weakness
Weight loss
Vomiting

Acute pancreatitis is sudden swelling and inflammation of the pancreas.

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals called enzymes, as well as the hormones insulin and glucagon. Most of the time, the enzymes are only active after they reach the small intestine, where they are needed to digest food.
When these enzymes somehow become active inside the pancreas, they eat (and digest) the tissue of the pancreas. This causes swelling, bleeding (hemorrhage), and damage to the pancreas and its blood vessels.
Acute pancreatitis affects men more often than women. Certain diseases, surgeries, and habits make you more likely to develop this condition.
The condition is most often caused by alcoholism and alcohol abuse (70% of cases in the United States). Genetics may be a factor in some cases.  Sometimes the cause is not known, however.

Other conditions that have been linked to pancreatitis are:

Autoimmune problems (when the immune system attacks the body)
Blockage of the pancreatic duct or common bile duct, the tubes that drain enzymes from the pancreas
Damage to the ducts or pancreas during surgery
High blood levels of a fat called triglycerides (hypertriglyceridemia)
Injury to the pancreas from an accident

Other causes include:

1. Complications of cystic fibrosis
2. Hemolytic uremic syndrome
3. Hyperparathyroidism
4. Kawasaki disease
5. Reye syndrome
6. Use of certain medications (especially estrogens, corticosteroids, thiazide diuretics, and azathioprine)
7. Viral infections, including mumps, coxsackie B, mycoplasma pneumonia, and campylobacter

Symptoms

The main symptom of pancreatitis is abdominal pain felt in the upper left side or middle of the abdomen.
The pain:

May be worse within minutes after eating or drinking at first, especially if foods have a high fat content
Becomes constant and more severe, lasting for several days
May be worse when lying flat on the back
May spread (radiate) to the back or below the left shoulder blade

People with acute pancreatitis often look ill and have a fever, nausea, vomiting, and sweating.
Other symptoms that may occur with this disease include:

1. Clay-colored stools
2. Gaseous abdominal fullness
3. Hiccups
4. Indigestion
5. Mild yellowing of the skin and whites of the eyes (jaundice)
6. Skin rash or sore (lesion)
7. Swollen abdomen

Treatment

Treatment often requires a stay in the hospital and may involve:

Pain medicines
Fluids given through a vein (IV)
Stopping food or fluid by mouth to limit the activity of the pancreas

Occasionally a tube will be inserted through the nose or mouth to remove the contents of the stomach (nasogastric suctioning). This may be done if vomiting or severe pain do not improve, or if a paralyzed bowel (paralytic ileus) develops.  The tube will stay in for 1 - 2 days to 1 - 2 weeks.

Treating the condition that caused the problem can prevent repeated attacks.
In some cases, therapy is needed to:

Drain fluid that has collected in or around the pancreas
Remove gallstones
Relieve blockages of the pancreatic duct

In the most severe cases, surgery is needed to remove dead or infected pancreatic tissue.
Avoid smoking, alcoholic drinks, and fatty foods after the attack has improved.
Expectations (prognosis)
Most cases go away in a week. However, some cases develop into a life-threatening illness.
The death rate is high with:

Hemorrhagic pancreatitis
Liver, heart, or kidney impairment
Necrotizing pancreatitis

Pancreatitis can return.  The likelihood of it returning depends on the cause, and how successfully it can be treated.

Complications

Acute kidney failure
Acute respiratory distress syndrome (ARDS)
Buildup of fluid in the abdomen (ascites)
Cysts or abscesses in the pancreas
Heart failure
Low blood pressure

Repeat episodes of acute pancreatitis can lead to chronic pancreatitis.

Chronic pancreatitis is inflammation of the pancreas that does not heal or improve, gets worse over time, and leads to permanent damage.

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals (called enzymes) needed to digest food. It also produces the hormones insulin and glucagon.
When inflammation and scarring of the pancreas occur, the organ is no longer able to make the right amount of these enzymes. As a result, your body may be unable to digest fat and other important parts of food.
Damage to the portions of the pancreas that make insulin may lead to diabetes.
The condition is most often caused by alcohol abuse over many years. Repeat episodes of acute pancreatitis can lead to chronic pancreatitis.  Genetics may be a factor in some cases. Sometimes the cause is not known.

Other conditions that have been linked to chronic pancreatitis:

• Autoimmune problems (when the immune system attacks the body)
• Blockage of the pancreatic duct or the common bile duct, the tubes that drain enzymes from the pancreas
• Complications of cystic fibrosis
• High levels of a fat called triglycerides in the blood (hypertriglyceridemia)
• Hyperparathyroidism

Use of certain medicationss (especially estrogens, corticosteroids, thiazide diuretics, and azathioprine)
Chronic pancreatitis occurs more often in men than in women.  The condition often develops in people ages 30 - 40.

Symptoms

• Abdominal pain
• Greatest in the upper abdomen
• May last from hours to days
• Eventually may be continuous
• May get worse from eating or drinking
• May get worse from drinking alcohol
• May also be felt in the back
• Digestive problems
• Chronic weight loss, even when eating habits and amounts are normal
• Diarrhea, nausea, and vomiting
• Fatty or oily stools
• Pale or clay-colored stools

The symptoms may become more frequent as the condition gets worse.  The symptoms may mimic pancreatic cancer.  Sitting up and leaning forward may sometimes relieve the abdominal pain of pancreatitis.

Tests for pancreatitis include:

• Fecal fat test
• Serum amylase
• Serum IgG4 (for diagnosing autoimmune pancreatitis)
• Serum lipase
• Serum trypsinogen
• Inflammation or calcium deposits of the pancreas, or changes to the ducts of the pancreas may be seen on:
• Abdominal CT scan
• Abdominal ultrasound
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Endoscopic ultrasound (EUS)
• Magnetic resonance cholangiopancreatography (MRCP)

An exploratory laparotomy may be done to confirm the diagnosis, but this is usually done for acute pancreatitis.

Treatment

People with severe pain or who are losing weight may need to stay in the hospital for:

• Pain medicines
• Fluids given through a vein (IV)

Stopping food or fluid by mouth to limit the activity of the pancreas, and then slowly starting an oral diet.  Inserting a tube through the nose or mouth to remove the contents of the stomach (nasogastric suctioning) may sometimes be done.  The tube may stay in for 1 - 2 days, or sometimes for 1 - 2 weeks.

Eating the right diet is important for people with chronic pancreatitis.  A nutritionist can help you create the best diet to maintain a healthy weight and receive the correct vitamins and minerals.   All patients should be:

• Drinking plenty of liquids
• Eating a low-fat diet
• Eating small, frequent meals (this helps reduce digestive symptoms)
• Getting enough vitamins and calcium in the diet, or as extra supplements
• Limiting caffeine

The doctor may prescribe pancreatic enzymes, which you must take with every meal. The enzymes will help you digest food better and gain weight.

Avoid smoking and drinking alcoholic beverages, even if your pancreatitis is mild.

Other treatments may involve:

Pain medicines or a surgical nerve block to relieve pain
Taking insulin to control blood sugar (glucose) levels
Surgery may be recommended if a blockage is found.  In severe cases, part or all of the pancreas may be removed.

Expectations (prognosis)

This is a serious disease that may lead to disability and death. You can reduce the risk by avoiding alcohol.

Complications

1. Ascites
2. Blockage (obstruction) of the small intestine or bile ducts
3. Blood clot in the vein of the spleen
4. Fluid collections in the pancreas (pancreatic pseudocysts) that may become infected
5. Poor function of the pancreas
6. Diabetes
7. Fat or other nutrient malabsorption
8. Vitamin malabsorption (most often the fat-soluble vitamins, A, D, E, or K)

Prevention

Determining the cause of acute pancreatitis and treating it quickly may help prevent chronic pancreatitis. Not drinking a lot of alcohol reduces the risk of developing this condition.

A pancreatic abscess is a cavity of pus within the pancreas.

Causes, incidence, and risk factors

Pancreatic abscesses develop in patients with pancreatic pseudocysts that become infected.
Symptoms

1. Abdominal mass
2. Abdominal pain
3. Chills
4. Fever
5. Inability to eat
6. Nausea and vomiting

Signs and tests

Patients with pancreatic abscesses usually have had pancreatitis. However, the complication often takes 7 or more days to develop.

Symptoms usually include:

• Abdominal pain
• Fever

Signs of an abscess can be seen on:

• CT scan
• MRI of the abdomen
• Ultrasound

Treatment

It may be possible to drain the abscess through the skin (percutaneous). Surgery to drain the abscess and remove dead tissue is often needed.

Expectations (prognosis)

How the person does depends on how severe the infection is.  The death rate from undrained pancreatic abscesses is very high.

Complications

1. Multiple abscesses
2. Sepsis

Causes, incidence, and risk factors

The pancreas is an organ located behind the stomach that produces chemicals (called enzymes) needed to digest food. It also produces the hormones insulin and glucagon.
Pancreatic pseudocysts most often develop after an episode of severe, acute pancreatitis.  Acute pancreatitis is sudden swelling (inflammation) of the pancreas.
It may also occur after trauma to the abdomen, more often in children.
The cyst happens when the ducts (tubes) in the pancreas are damaged by the inflammation or swelling that occurs during pancreatitis.
A pancreatic pseudocyst may also occur after trauma to the abdomen, and in someone with chronic pancreatitis.

Symptoms

Symptoms can occur within days to months after an attack of pancreatitis, and include:

• Bloating of the abdomen
• Constant pain or deep ache in the abdomen, which may also be felt in the back
• Difficulty eating and digesting food

Treatment

Treatment depends on the size of the pseudocyst and whether it is causing symptoms.  Many pseudocysts go away on their own.  Those that remain for more than 6 weeks and are larger than 5 cm in diameter often need surgery.

Surgical treatments include:

• Drainage through the skin (percutaneous) using a needle, usually guided by a CT scan
• Endoscopic-assisted drainage using an endoscope (a tube containing a camera and a light that is passed down into the stomach)
• Surgical drainage of the pseudocyst, which involves making a connection between the cyst and the stomach or small intestine.  This may be done using a laparoscope.

Expectations (prognosis)

The outcome is generally good with treatment.

Calling your health care provider

Rupture of the pseudocyst is an emergency situation.  Go to the emergency room or call the local emergency number (such as 911) if you develop symptoms of bleeding or shock, such as:

• Fainting
• Fever and chills
• Rapid heartbeat
• Severe abdominal pain

Prevention

The way to prevent pancreatic pseudocysts is by preventing pancreatitis.  I f pancreatitis is caused by gallstones, it is usually necessary to remove the gallbladder with surgery (cholecystectomy).  When pancreatitis occurs due to alcohol abuse, the patient must stop drinking alcohol to prevent future attacks.

References :

---

Christoph W Michalski, Tamara Laukert, Danguole Sauliunaite, Pál Pacher, Frank Bergmann, Gastroenterology (2007)
Volume: 132, Issue: 5, Pages: 1968-1978
Michalski CW, Laukert T, Sauliunaite D, Pacher P, Bergmann F, Agarwal N, Su Y, Giese T, Giese NA, Bátkai S, Friess H, Kuner R.
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Kazuhisa Matsuda1), Yukio Mikami1), Kazunori Takeda1), Shoji Fukuyama1), Shinichi Egawa1), Makoto Sunamura1), Ikurou Maruyama2) and Seiki Matsuno1)

1) Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine
2) Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University Christoph W. Michalski1,2#*, Milena Maier2#, Mert Erkan1#,Danguole Sauliunaite1, Frank Bergmann3, Pal Pacher4,Sandor Batkai4, Nathalia A. Giese2, Thomas Giese5, Helmut Friess1, Jörg Kleeff1
1 Department of Surgery, Technische Universität München, Munich, Germany,2 Department of General Surgery, University of Heidelberg, Heidelberg, Germany, 3 Institute of Pathology, University of Heidelberg, Heidelberg, Germany, 4 Section of Oxidative Stress Tissue Injury, Laboratory of Physiologic Studies, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland, United States of America, 5 Institute of Immunology, University of Heidelberg, Heidelberg, Germany
Di Sebastiano P, di Mola FF, Buchler MW, Friess H (2004) Pathogenesis of pain in chronic pancreatitis. Dig Dis 22: 267–272. FIND THIS ARTICLE ONLINE
Friess H, Kleeff J, Buchler MW (2003) Molecular pathophysiology of chronic pancreatitis–an update. J Gastrointest Surg 7: 943–945. FIND THIS ARTICLE ONLINE
Whitcomb DC (2004) Mechanisms of disease: Advances in understanding the mechanisms leading to chronic pancreatitis. Nat Clin Pract Gastroenterol Hepatol 1: 46–52. FIND THIS ARTICLE ONLINE
Hartel M, Tempia-Caliera AA, Wente MN, Z'Graggen K, Friess H, et al. (2003) Evidence-based surgery in chronic pancreatitis. Langenbecks Arch Surg 388: 132–139. FIND THIS ARTICLE ONLINE
Esposito I, Friess H, Buchler MW (2001) Molecular mechanisms in chronic pancreatitis. Zentralbl Chir 126: 867–872. FIND THIS ARTICLE ONLINE
Apte MV, Park S, Phillips PA, Santucci N, Goldstein D, et al. (2004) Desmoplastic reaction in pancreatic cancer: role of pancreatic stellate cells. Pancreas 29: 179–187. FIND THIS ARTICLE ONLINE
Ceyhan GO, Bergmann F, Kadihasanoglu M, Erkan M, Park W, et al. (2007) The neurotrophic factor artemin influences the extent of neural damage and growth in chronic pancreatitis. Gut 56: 534–544. FIND THIS ARTICLE ONLINE
Bockman DE, Buchler M, Malfertheiner P, Beger HG (1988) Analysis of nerves in chronic pancreatitis. Gastroenterology 94: 1459–1469. FIND THIS ARTICLE ONLINE
Michalski CW, Selvaggi F, Bartel M, Mitkus T, Gorbachevski A, et al. (2007) Altered anti-inflammatory response of mononuclear cells to neuropeptide PACAP is associated with deregulation of NF-kappaB in chronic pancreatitis. Am J Physiol Gastrointest Liver Physiol 294: G50–7. FIND THIS ARTICLE ONLINE
Apte MV, Haber PS, Applegate TL, Norton ID, McCaughan GW, et al. (1998) Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut 43: 128–133. FIND THIS ARTICLE ONLINE
Bachem MG, Schneider E, Gross H, Weidenbach H, Schmid RM, et al. (1998) Identification, culture, and characterization of pancreatic stellate cells in rats and humans. Gastroenterology 115: 421–432. FIND THIS ARTICLE ONLINE
Phillips PA, McCarroll JA, Park S, Wu MJ, Pirola R, et al. (2003) Rat pancreatic stellate cells secrete matrix metalloproteinases: implications for extracellular matrix turnover. Gut 52: 275–282. FIND THIS ARTICLE ONLINE
Shimizu K, Kobayashi M, Tahara J, Shiratori K (2005) Cytokines and peroxisome proliferator-activated receptor gamma ligand regulate phagocytosis by pancreatic stellate cells. Gastroenterology 128: 2105–2118. FIND THIS ARTICLE ONLINE
Mews P, Phillips P, Fahmy R, Korsten M, Pirola R, et al. (2002) Pancreatic stellate cells respond to inflammatory cytokines: potential role in chronic pancreatitis. Gut 50: 535–541. FIND THIS ARTICLE ONLINE
Apte MV, Haber PS, Darby SJ, Rodgers SC, McCaughan GW, et al. (1999) Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis. Gut 44: 534–541. FIND THIS ARTICLE ONLINE
Phillips PA, Wu MJ, Kumar RK, Doherty E, McCarroll JA, et al. (2003) Cell migration: a novel aspect of pancreatic stellate cell biology. Gut 52: 677–682. FIND THIS ARTICLE ONLINE
Michalski CW, Shi X, Reiser C, Fachinger P, Zimmermann A, et al. (2007) Neurokinin-2 Receptor Levels Correlate With Intensity, Frequency, and Duration of Pain in Chronic Pancreatitis. Ann Surg 246: 786–793. FIND THIS ARTICLE ONLINE
Haber PS, Keogh GW, Apte MV, Moran CS, Stewart NL, et al. (1999) Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis. Am J Pathol 155: 1087–1095. FIND THIS ARTICLE ONLINE
Apte MV, Wilson JS (2004) Mechanisms of pancreatic fibrosis. Dig Dis 22: 273–279. FIND THIS ARTICLE ONLINE
Omary MB, Lugea A, Lowe AW, Pandol SJ (2007) The pancreatic stellate cell: a star on the rise in pancreatic diseases. J Clin Invest 117: 50–59. FIND THIS ARTICLE ONLINE
DiMagno MJ, Dimagno EP (2006) Chronic pancreatitis. Curr Opin Gastroenterol 22: 487–497. FIND THIS ARTICLE ONLINE
Talukdar R, Saikia N, Singal DK, Tandon R (2006) Chronic pancreatitis: evolving paradigms. Pancreatology 6: 440–449. FIND THIS ARTICLE ONLINE
van Esch AA, Wilder-Smith OH, Jansen JB, van Goor H, Drenth JP (2006) Pharmacological management of pain in chronic pancreatitis. Dig Liver Dis 38: 518–526. FIND THIS ARTICLE ONLINE
Pacher P, Batkai S, Kun
S, Friess H, Kuner R
Department of General Surgery, University of Heidelberg, Heidelberg, Germany.
Gastroenterology [2007, 132(5):1968-78]
Type:  Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Intramural
DOI: 10.1053/j.gastro.2007.02.035 
1. Kumar RN, Chambers WA, Pertwee RG. Pharmacological actions and therapeutic uses of
cannabis and cannabinoids. Anesthesia 2001; 56: 1059-1068.
2. Mechoulam R, Gaoni Y. A total synthesis of dl-delta-1-tetrahydrocannabinol, the active
constituent of hashish. J Am Chem Soc 1965; 87: 3273-3275.
3. Pertwee RG. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 1997;
74: 129-180.
4. Devane WA, Dymarz FA 3rd, Johnson MR, Melin LS, Howlett AC. Determination and
characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 1988; 34: 605-13.
5. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid
receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561-564.
6. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for
cannabinoids. Nature 1993; 365: 61-65.
7. Dewane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds
to the cannabinoid receptor. Science 1992; 258:1946-1949.
8. Howlett AC, Barth F, Bonner TI, et al. International Union of Pharmacology. XXVII.

 Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006 Oct;101(10):2379-400. [PubMed]
. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet. 2008;371:143-152. [PubMed]
. Owyang C. Pancreatitis. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 147.