Chronic pancreatitis - Causes, symptoms and treatment. MF.

Reasons
Symptoms of chronic pancreatitis
Diagnosis
Treatment of chronic pancreatitis
Complications and prognosis

Chronic pancreatitis is a group of variants of pancreatic disease characterized by the presence of focal necrosis in the pancreas against a background of segmental fibrosis with impairment of glandular functions of varying severity. Progression of chronic pancreatitis leads to the appearance and development of atrophy( depletion) of the glandular tissue, fibrosis and replacement of the cellular elements of the pancreatic parenchyma by the connective tissue.

The main causes of chronic pancreatitis:

1) alcohol consumption - alcoholic pancreatitis( more often in men older than 35 years) at a dose of more than 20-80 mg ethanol / day.for 8-12 years. The protein diet and smoking further aggravate the course of pancreatitis;
2) diseases of the biliary tract and duodenum - biliary pancreatitis( more often in women);
• cholelithiasis is the cause of chronic pancreatitis in 35-56% of cases;

• pathology of the sphincter of Oddi( stenosis, stricture, inflammation, swelling);
• duodenitis and peptic ulcer. So, duodenal ulcer in 10,5-16,5% of cases is the direct cause of the development of chronic pancreatitis.

Chronic pancreatitis, which develops with cholelithiasis, choledocholithiasis, is more common in women 50 to 60 years of age. Typically, these patients have signs of a metabolic syndrome: obesity, hyperlipidemia, a tendency to hypertension, coronary artery disease, a violation of carbohydrate tolerance, hyperuricemia and / or hyperuricosuria.

These 2 points are most likely and most often cause chronic pancreatitis. The least common causes:

3) cystic fibrosis( often in children);
4) hereditary pancreatitis. The most common in Northern Europe, its frequency is about 5% of all cases. To suspect an hereditary form of pancreatitis allows the absence of apparent causes and cases of pancreatitis in the family of the relatives of the patient;
5) idiopathic pancreatitis. When at the time of the study the cause is not established - 10 to 30% of all pancreatitis. Recent studies have shown that the cause of idiopathic pancreatitis can be microcrystals of cholesterol, granules of bilirubin and calcium microspherolites;
6) Other causes:
• autoimmune pancreatitis,
• systemic diseases and vasculitis,
• viral( Coxsackie, CMV) and bacterial infections,
• helminthic invasion( opisthorchiasis),
• metabolic disorders( hyperlipidemia, diabetes mellitus, CRF andetc.),
• discirculatory disorders( ischemic pancreatitis),
• pancreatic abnormalities,
• trauma, acute poisoning.

Symptoms of chronic pancreatitis

Chronic pancreatitis is a slowly progressing inflammatory disease of the pancreas, accompanied by necrosis( necrosis of the gland tissue) in combination with fibrosis and leading to a progressive deterioration of the organ function even after the cessation of the pathogenic effect that led to the disease. Conventionally, chronic pancreatitis is said when the inflammatory process in the pancreas lasts more than 6 months. Chronic pancreatitis usually occurs with episodes of exacerbations and remissions( remission of the disease).

It is important to distinguish between acute and chronic pancreatitis, since there are fundamental differences in the tactics of treating such patients. This is sometimes extremely difficult, because the exacerbation of chronic pancreatitis is very similar in its symptoms to acute pancreatitis, and acute pancreatitis, in turn, may remain unrecognized( in 60% of cases!), Flowing under the masks of other diseases of the gastrointestinal tract or in their accompaniment, and already then will pass in chronic.

Options for chronic pancreatitis

Chronic obstructive pancreatitis develops as a result of obstruction of the main duct of the pancreas by a tumor, inflammation of the duodenal papilla or its stenosis, duodenitis due to Crohn's disease, closed abdominal trauma and surgical operations in the pyloroduodenal zone, pseudocyst of the pancreas, congenital anomaly( doubling of the duct).Gallstone disease and choledocholithiasis, dysfunction of the Oddi sphincter of the biliary and pancreatic types are the main causes of the formation of chronic obstructive pancreatitis. The defeat of the pancreas is uniform and is not accompanied by the formation of stones inside the ducts of the gland. The leading symptom is a permanent pain syndrome.

Calcificating chronic pancreatitis in the ducts shows protein precipitates or calcifications, stones, cysts and pseudocysts, stenosis and atresia, as well as atrophy of acinar tissue. For this form of chronic pancreatitis is characterized by a recurrent course with episodes of exacerbation, at an early stage resembling acute pancreatitis( chronic recurrent pancreatitis).As a rule, such a chronic pancreatitis has the first cause of drinking alcohol.

The group of calcifying pancreatitis represents alcoholic pancreatitis, pancreatitis, which develops under the influence of organic solvents, some chemical compounds, drugs, as well as pancreatitis that began as a result of hyperlipidemia, hypercalcemia in hyperparathyroidism, chronic viral infections( including chronic HCV and HBV infection), congenital changes in the pancreatic ducts( doubling the pancreatic duct).

Hereditary pancreatitis with autosomal dominant type of inheritance with incomplete penetration also belongs to the group of calcific pancreatitis and develops in children 10-12 years old or at the age of 30-40 years. It is indistinguishable from the usual forms of pancreatitis, accompanied by recurrent attacks of abdominal pain, after 8-10 years, in 20% of patients diabetes mellitus joins and in 15-20% of patients - pronounced steatorrhea. The absence of other causes and an indication of cases of pancreatitis in the family make it reasonable to suspect a hereditary form of chronic pancreatitis.

Chronic parenchymal pancreatitis is characterized by the development of foci of inflammation in the parenchyma, with predominance of mononuclear cells and fibrosis in the infiltrates that replace the parenchyma of the pancreas. With this form of chronic pancreatitis there are no lesions of ducts and calcifications in the pancreas. Leading symptoms are slowly progressing signs of exocrine and endocrine insufficiency and the absence of pain syndrome( painless form).

The most common clinical syndromes for chronic pancreatitis are:

• pain abdominal syndrome,
• pancreatic gland secretion syndrome,
• endocrine disability syndrome,
• dyspeptic syndrome,
• biliary hypertension syndrome.

Pain in chronic pancreatitis

Often the development of a painful form of chronic pancreatitis is preceded by painless, latent stage of various duration, disguised as epigastric discomfort, flatulence, unstable stool with a tendency to diarrhea with undigested fiber in the stool or steatori. Repeated attacks of the painful form of chronic pancreatitis form pancreatic insufficiency with the predominant lesion of exocrine or endocrine functions with the development of type 2 diabetes.

Pain can occur both during exacerbation and in the phase of remission of chronic pancreatitis. It does not have a clear localization, occurs in the upper or middle abdomen on the left or in the middle, it gives back, sometimes it takes a shingling character. More than half of the patients have very intense pain.

Pain localization in chronic pancreatitis

The causes of pain in chronic pancreatitis are as follows:

1) Acute inflammation of the pancreas( damage to the parenchyma and capsule);
2) pseudocysts with perifocal inflammation;
3) obstruction and dilatation of pancreatic and bile duct;
4) fibrosis in the sensory nerve region, leading to their compression;
5) pressure on the surrounding nerve plexuses of the enlarged pancreas;
- stenosis and dyskinesia of the sphincter of Oddi.
- Pain associated with pseudocysts and obstruction of the ducts is greatly amplified during or immediately after eating. Pain, as a rule, is shrouded, paroxysmal. Significantly reduce the pain of antisecretory drugs and preparations of pancreatin( Pansinorm), which reduce pancreatic secretion by the feedback mechanism.
- Inflammatory pains do not depend on food intake, are localized, as a rule, in epigastrium, irradiate into the back. Such pains are relieved by analgesics( NSAIDs, in severe cases - narcotic analgesics)
- External pancreatic insufficiency leads to excess bacterial growth in the small intestine, which is also the cause of pain in a significant proportion of patients with chronic pancreatitis. These pains are caused by increased pressure in the duodenum.

In the later stages of chronic pancreatitis, with the development of fibrosis, pain decreases and in a few years can disappear. Then manifestations of exocrine insufficiency come to the fore.

Symptoms of exocrine insufficiency

External pancreatic insufficiency is a violation of intestinal digestion and absorption. Symptoms:

• diarrhea( stool 3 to 6 times a day),
• steatorrhea( occurs when the pancreatic secretion is reduced by 10%, feces are crispy, offensive, with a greasy shine).
• weight loss,
• nausea,
• recurrent vomiting,
• loss of appetite.

The syndrome of excess bacterial growth in the small intestine develops quite quickly, its symptoms:

• flatulence,
• rumbling in the abdomen,
• belching.

Later, symptoms associated with hypovitaminosis - anemia, weakness, changes in the skin, hair, metabolism - are added.

The following mechanisms are based on the external pancreatic insufficiency of the pancreas:

- destruction of acinar cells, resulting in a decrease in the synthesis of pancreatic enzymes;
- obstruction of the pancreatic duct, which disrupts the entry of pancreatic juice into the duodenum;
- a decrease in the secretion of bicarbonates by the epithelium of the gland ducts leads to acidification of the contents of the duodenum to a pH of 4 or lower, resulting in the denaturation of pancreatic enzymes and the precipitation of bile acids.

Symptoms of biliary hypertension

The syndrome of biliary hypertension is expressed in mechanical jaundice and cholangitis and is relatively rare. Up to 30% of patients in the stage of exacerbation of chronic pancreatitis have transient or persistent hyperbilirubinemia. Causes of the syndrome - an increase in the head of the pancreas with compression of the terminal section of choledochoma, choledocholithiasis and pathology of the large duodenal papilla( concrements, stenosis).

Symptoms of endocrine disorders in chronic pancreatitis

Are detected in about a third of patients. At the heart of the development of these disorders is the defeat of all cells of the islet apparatus of the pancreas, as a result of which there is a deficit of not only insulin, but also glucagon. This explains the features of the course of pancreatogenic diabetes mellitus: a tendency to hypoglycemia, the need for low doses of insulin, a rare development of ketoacidosis, vascular and other complications.

Symptoms of chronic pancreatitis caused by the enzyme

• Intoxication syndrome manifests general weakness, decreased appetite, hypotension, tachycardia, fever, leukocytosis and increased ESR.
• Symptom Tuzhilin( symptom of "red droplets"): the appearance of bright red spots on the skin of the chest, back, abdomen. These spots are vascular aneurysms and do not disappear when pressed.

Diagnosis of chronic pancreatitis

Diagnosis of chronic pancreatitis is quite complex and is based on 3 main symptoms: a characteristic history( painful attacks, alcohol abuse), the presence of exocrine and / or endocrine insufficiency and the identification of structural changes in the pancreas. Often, the diagnosis of chronic pancreatitis is formed after a long observation of a patient who has clinical signs suggesting the presence of chronic pancreatitis.

Laboratory diagnostics

Blood for biochemistry. The level of amylase, serum lipase more often remains normal or decreased during the attack of pancreatitis, which is explained by a decrease in the number of acinar cells producing these enzymes. When alcohol pancreatitis is combined with alcoholic liver disease, broken functional liver tests can be detected. In 5-10% of cases of chronic pancreatitis, there are signs of compression of the intra-pancreatic part of the bile duct caused by edema or fibrosis of the head of the pancreas, which is accompanied by jaundice, increased levels of direct bilirubin and serum alkaline phosphatase.

The violation of glucose tolerance develops in 2/3 of patients, diabetes mellitus - in 30% of patients with chronic pancreatitis.

Exocrine insufficiency becomes evident and is easily detected with the development of the syndrome of impaired absorption, in which the fat in the stool can be determined qualitatively( coloring in Sudan) or quantitatively. Secretory insufficiency at earlier stages is revealed with the help of pancreatic functional tests.

In the clinical practice for the diagnosis of chronic pancreatitis, an enzyme immunoassay is used to determine elastase-1 in the blood serum and feces of patients, which makes it possible to evaluate the exocrine function of the pancreas.

Instrumental diagnosis of chronic pancreatitis

Instrumental data to confirm the assumption of the presence of chronic pancreatitis can be considered quite informative. Used:

- ultrasound examination of the abdominal cavity;
- endoscopic ultrasound, spiral computer and magnetic resonance imaging of the pancreas.

ERCP can detect duct stenosis, obstruction localization, structural changes in small ducts, in-flow calcifications and protein corks, but there is a high risk of acute pancreatitis

Differential diagnosis of pancreatitis

Symptoms of pancreatitis refer to signs of "acute abdomen".This means that it is necessary to distinguish pancreatitis from acute surgical pathology of the abdominal cavity, namely: from the perforated ulcer;acute cholecystitis;intestinal obstruction;thrombosis of the intestinal veins;myocardial infarction.

Perforating ulcer. Perforation( perforation) of a stomach ulcer or intestine differs from acute pancreatitis with "dagger pain".This pain is associated with the penetration of gastric or intestinal contents on the peritoneum, which causes reflex tension in the anterior abdominal wall, or the so-called flaky abdomen. For pancreatitis this is not typical. Vomiting during perforation of ulcers is extremely rare. The patient lies motionless. And the patient with pancreatitis is restless, rushes in bed. An overview radiograph indicates a gas in the abdominal cavity with a perforated ulcer. The final diagnosis is made on the basis of ultrasound or laparoscopy.

Acute cholecystitis. It can be difficult to distinguish between these two pathologies. But in favor of cholecystitis, the predominant localization of pain on the right with irradiation to the right shoulder region will be spoken. When performing ultrasound, you can determine the localization of inflammation, but it is worth remembering that pancreatitis can accompany cholecystitis.

Acute intestinal obstruction. Pain with intestinal obstruction is cramping, and with pancreatitis the pain is constant, aching. On the roentgenogram with pancreatitis, the large intestine will be swollen, but without the Klauber bowls.

Mesothrombosis. Mesothrombosis most often affects the elderly with cardiovascular pathology. Symptoms in this case are increasing rapidly, but they have nothing to do with eating. Laparoscopy or angiography will help resolve doubts.

Myocardial infarction. Upon arrival in the hospital, electrocardiography is routinely performed, it is not difficult to distinguish pancreatitis from myocardial infarction.

Treatment of chronic pancreatitis

Treatment of uncomplicated chronic pancreatitis can be performed in an outpatient setting under the guidance of a gastroenterologist or therapist.

The goal of treating chronic pancreatitis can be considered the solution of several problems:

- elimination of provoking factors( alcohol, drugs, obstruction);
- pain relief;
- correction of exo- and endocrine insufficiency;
- treatment of concomitant disorders.

The main goals of conservative treatment are to stop or slow the progression of chronic pancreatitis and combat its complications. Depending on the severity of pain abdominal syndrome, a phased treatment of chronic pancreatitis is used, which may include the following components:

- Diet, fractional nutrition, fats less than 60 g / day.
- Pancreatic enzymes( pancreatin, creon, mezim, panzinorm, festal, penzital, enzyme) + H2-blockers( famotidine, ranitidine, cimetidine, nizatidine).
- Non-narcotic analgesics( acetylsalicylic acid, diclofenac, ibuprofen, piroxicam).
- Octreotide( sandostatin).
- Endoscopic drainage( Olimpus, LOMO, Pentax, Fujinon).
- Narcotic analgesics( butorphanol, antaksa, fortal, tramadol, sedalgin-neo).
- Blockade of the solar plexus.
- Surgical intervention.

With a weak pain syndrome, success can be achieved through a strict diet, a fractional( every 3 hours) meal and a fat restriction of up to 60 grams per day, which helps reduce pancreatic secretion in a low-calorie diet.

Drugs for the treatment of chronic pancreatitis

Given the fact that the main cause of pain is intraprostatic hypertension, it is advisable to use drugs that block stimulated pancreatic secretion. Normally, the release of cholecystokinin, the main stimulant of the exogenous function of the pancreas, is regulated by cholecystokinin-releasing peptide in the proximal small intestine, which is sensitive to trypsin and is active in the lumen of the gut. The administration of pancreatic enzymes( mezim forte, pancreatin, panzinorma, lercrease pancreatite) provides significant relief of pain in some patients due to the inclusion of a feedback mechanism: increasing the level of proteases in the lumen of the duodenum reduces the release and synthesis of gastrointestinal hormones( cholecystokinin), which leads to a decreasestimulation of the exocrine function of the pancreas, reduction of intra-flow and tissue pressure, and pain relief.

It should be remembered the possibility of inactivation of exogenous digestive enzymes by stomach acid and pancreatic proteases. To prevent this effect, a combination of enzymes( pancreatin, creon, mezim, panzinorm, festal, penzital, enzyme) with H2-histaminoblockers( famotidine, ranitidine, cimetidine, nizatidine) is widely used. Doses of enzyme preparations for pain relief should be adequate;in a placebo-controlled, double-blind study of pancreolipase at a dose of 6 tablets 4 times a day for 1 month significantly reduced pain in 75% of patients with mild and severe pancreatitis. Pancreatic enzymes in a capsule form containing acid-fast mini-microspheres( creon) are currently the first choice drugs in the treatment of abdominal pain in exocrine pancreatic insufficiency. Microgranular dosage forms( creel 10000 or 25000) are characterized by rapid release( after 45 minutes) of more than 90% of enzymes at a pH of duodenal and intestinal contents of 5.5 and above.

At very low pH values, adjuvant therapy with H2 antagonists or proton pump inhibitors( lansoprazole, omeprazole, pantoprazole, rabeprozole) is used in the gastrointestinal tract. In addition, it has been shown that enzyme replacement therapy improves the transit of food through the gastrointestinal tract, affecting the motor function of the gastrointestinal tract and thereby contributing to a decrease in absorption disorders.

Pancreatic enzymes are prescribed in all cases of chronic pancreatitis to correct exocrine pancreatic function. The intake of these drugs reduces the bowel tension and diarrhea caused by a violation of fat absorption, and therefore the pain decreases. Enzyme drugs reduce the intensity of pain in chronic pancreatitis of moderate severity, especially in women with obstructive pancreatitis;against the background of doubling the pancreatic duct. In men with alcoholic calcific pancreatitis, these drugs are much less effective.

For cupping a steatorrhoea in chronic pancreatitis, preparations with a high lipase content, coated with a coating, are indicated;for relief of pain - drugs with a high content of proteases without a coat.

In the absence of the effect of enzyme replacement therapy in combination with H2-histamin blockers, the appointment of analgesics is necessary, paracetamol( darron, prodrugol, efflergan), non-steroidal anti-inflammatory drugs: diclofenac( apo-diclou, voltaren, diclofenac, orthophene), ibuprofenapo-ibuprofen, ibuprofen, ibuphen, solpaflex), piroxicam( piroxicam, pyroxypher, felden, erazon), celecoxib( celebrex), lornoxicam( ksefokam), meloxicam( meloxicam, movalis), nimesulide( mesulide, nyz, nikuld), naproxen( apo-naproxen Bonifen, naproxen).

To stop pain in chronic pancreatitis octreotide is prescribed( sandostatin).Being a powerful inhibitor of neuroendocrine hormones in the gastrointestinal tract, sandostatin suppresses the exogenous and endogenous stimulated exocrine pancreatic secretion by direct action on the exocrine tissue and reduces the release of secretin and cholecystokinin. The drug is also effective in the treatment of pseudocysts, pancreatic ascites and pleurisy. It is used 50-100 mcg subcutaneously 2 times a day for 1 week to treat the painful form of chronic pancreatitis.

With preservation of the pain syndrome, it is necessary to carry out ERPHG for morphological clarification of the nature of the defeat of the ducts, exclusion of the sphincter of Oddi dysfunction. In this case, the possibility of using invasive methods of treatment is discussed: endoscopic drainage and shunting, blockade of the solar plexus by steroids, pancreaticunostomy and pancreatic resection.

The greatest difficulties are associated with the treatment of dysfunction of the sphincter of Oddi, one of the causes of the development of chronic pancreatitis, difficult for diagnosis. With dysfunction of the sphincter of Oddi, the sensitivity of the wall of the pancreatic and bile ducts to changes in volume and pressure is noted.

It is necessary to exclude drugs that have a choleretic effect( bile acids, including enzymes, festal, enzyme, etc., decoctions of cholagogue grasses, synthetic cholagogue).

Nitrates are used to relieve the spasm of the smooth muscles of Oddi sphincters and the cystic duct: nitroglycerin - for rapid pain relief, nitrosorbite - for course treatment( under the control of drug tolerance).

Myotropic antispasmodics( bendazole, benzyclan, drotaverin, mebeverin, papaverine) reduce the tone and motor activity of smooth muscles. The main representatives of this group are papaverine, drotaverin( no-shpa, no-spha forte, vero-drotaverin, spasmol, spakovin), bcyciklan( halidor).The most effective myotropic antispasmodic is duspatalin( mebeverin) - a muscle-tropic, antispastic drug, which has a direct effect on smooth muscle. Selectively acting on the sphincter of Oddi, he is 20-40 times more effective than papaverine in terms of the ability to relax the sphincter of Oddi. It is important that duspatalin does not affect the cholinergic system and therefore does not cause such side effects as dry mouth, visual impairment, tachycardia, urinary retention, constipation and weakness. It is actively metabolized when passing through the liver, all metabolites are rapidly excreted in the urine. Complete excretion of the drug occurs within 24 hours after taking a single dose, as a result, it does not accumulate in the body, even elderly patients do not need a dose adjustment. Duspatalin is prescribed for 1 capsule( 200 mg) 2 times a day, it is better to take it 20 minutes before eating.

Another myotropic antispasmodic having selective properties is gimecromone( claston), a phenolic derivative of coumarin that does not have the properties of anticoagulants and has a pronounced spasmolytic and choleretic effect. Gimecromone is a synthetic analogue of umbelliferone found in fruits of anise and fennel, which were used as antispasmodics. The drug provides this or that effect depending on the characteristics of its action at different levels of the biliary tract. Odeston causes dilatation of the gallbladder, reduces intraprotective pressure and, thus, is an antagonist of cholecystokinin. At the level of the sphincter of Oddi, he acts synergistically with cholecystokinin, reduces basal pressure and increases the duration of the opening of the sphincter of Oddi, thereby increasing the bile passage through the bile ducts. Being highly selective antispasmodic, claston possesses also choleretic properties. Its choleretic effect is due to the acceleration and increase of bile flow into the small intestine. Increase in the intake of bile in the lumen of the duodenum promotes the improvement of digestion, activation of intestinal peristalsis and normalization of the stool.
Odeston is prescribed 400 mg( 2 tablets) 3 times a day for 30 minutes before meals, which provides a relatively constant concentration of the drug in the serum, exceeding 1.0 μg / ml. Duration of treatment is individual - from 1 to 3 weeks. Odeston is low in toxicity, its tolerability is usually good.

In the absence of the effect of conservative therapy of dysfunction of the sphincter of Oddi and the availability of data on its stenosis, the restoration of the sphincter of Oddi is performed operatively( sphincterotomy).

Substitution therapy for chronic pancreatitis

Substitution therapy for exocrine pancreatic insufficiency in the outcome of chronic pancreatitis is carried out with the presence of steatorrhea more than 15 grams of fat per day, progressive weight loss and dyspepsia. A single dose of enzymes should contain at least 20 000-40 000 units of lipase, so it is prescribed for 2-4 capsules at basic meals and 1-2 capsules with additional meals of a small amount of food. With clinically pronounced pancreatic insufficiency, it is often not possible to eliminate steatori completely. An increase in body weight, normalization of the stool, decrease in flatulence testify to the adequacy of the selected dose of digestive enzymes.

Inefficiency of substitution therapy requires the exclusion of other causes of the syndrome of impaired absorption - Crohn's disease, celiac disease, thyrotoxicosis. To correct the nutritional deficiency, medium-chain triglycerides( trisorbon) and fat-soluble vitamins A, D, E, K are prescribed.

Complications of chronic pancreatitis

Complications of chronic pancreatitis include impaired suction syndrome, diabetes mellitus, pseudocysts, thrombosis of portal or splenic vein, stenosis of pylorus, obstructioncommon bile duct and swelling. Adenocarcinoma of the pancreas develops in 4% of cases in individuals with more than 20 years of history of chronic pancreatitis.

Forecast

Mortality rate for chronic pancreatitis reaches 50% with a 20-25-year period of the disease.15-20% of patients die from complications associated with exacerbations of pancreatitis, other deaths are caused by trauma, eating disorders, infection, smoking, which are often observed in patients with chronic pancreatitis.