Pancreatic insufficiency, types, causes, treatment

In this article we will tell you:

1. What are enzymes
2. Enzyme system deficiency - genetics or the result of poor nutrition
3. How do digestive enzymes work?
4. What digestive enzymes are produced in the human body
5. The pancreas is an enzyme station
6. Top 15 Enzyme Rich Foods
7. Symptoms of enzyme deficiency
8. Tests to assess enzyme levels
9. Treatment of enzyme deficiency
10. When is enzyme supplementation indicated?
11. Types of Enzyme Supplements
12. Recommendations for taking enzymes

The first discussions about the importance of enzymes began thousands of years ago! One of the earliest written references to enzymes is found in the Greek poems of Homer, dating back to around 800 BC, where enzymes were mentioned as being used in the production of cheese.

What are enzymes

Enzymes

- These are protein substances that act as catalysts that accelerate chemical reactions. They are active under special conditions:

1. temperature should be 37-39 C;
2. when boiled they are destroyed;
3. depend on the environment: salivary and pancreatic enzymes are active in a slightly alkaline environment, stomach enzymes are active in an acidic environment.

Enzymes are known to catalyze about 4,000 biochemical reactions in living organisms. The rate of most enzymatic reactions is millions of times faster than the rate of uncatalyzed reactions. They can transform reactions in a matter of seconds and in the absence of enzymes these processes can take hundreds of years!

Where do the names of certain types of enzymes come from? It's simple - most often the suffix “aza” is added to the name of the substrate with which the reaction occurs, or to the name of the type of reaction they catalyze. For example, the enzyme urease catalyzes the hydrolysis of urea, and tyrosinase catalyzes the synthesis of melanin and other pigments from their precursor tyrosine. There are exceptions to all rules, the same here - pepsin and trypsin do not have standard suffixes, but also belong to the class of enzymes.

Classification of enzymes depending on the type of reaction catalyzed

:

• Oxidoreductases

  – redox reactions. In turn, they are divided into 17 subclasses. All enzymes contain a protein part and a non-protein part in the form of heme or derivatives of the vitamins riboflavin (B2), pantothenic acid (B5). For example, the liver enzyme cytochrome, which is part of this class, hydroxylates lipophilic xenobiotics (substances foreign to the body).

• Transferases

  – are responsible for the transfer of radicals from one molecule to another. For example, a representative of acyltransferase, coenzyme A, transfers an acyl group and forms the neurotransmitter acetylcholine.

• Hydrolases

  – catalyze hydrolysis reactions, that is, the breakdown of substances with the addition of a water molecule. This class includes predominantly digestive enzymes; they do not contain a non-protein part. Thus, amylase actively participates in reactions with carbohydrates and breaks down starches into oligosaccharides. And lactase is capable of hydrolyzing lactose (milk sugar) into two components - galactose and glucose. It is produced by various microorganisms and is also synthesized in the small intestine of humans and other mammals, helping to completely digest milk.

• Lyases

  – catalyze splitting reactions without adding a water molecule. These enzymes have a non-protein part in the form of thiamine pyrophosphate (B1) and pyridoxal phosphate (B6).

• Ligases

  – catalyze reactions of synthesis of complex substances from simple ones. Such reactions require the energy of ATP. The name of the enzymes of this group is added “synthetase” - ATP synthetase catalyzes the formation of the energy storage molecule adenosine triphosphate (ATP) using adenosine diphosphate (ADP) and inorganic phosphate.

• Isomerases

  – catalyze isomerization reactions.

As we have already found out, the vast majority of enzymes are proteins. But many representatives of enzymes require the presence of non-protein substances - cofactors - to exhibit catalytic activity. There are two groups of cofactors: metal ions (such as Fe3+, Mg2+, Mn2+ or Zn2+) and coenzymes.

Coenzymes

are small organic compounds that bind to the active site of enzymes, change the structure of the substrate, or transfer electrons, protons, and chemical groups between the enzyme and the substrate. To make the mechanism more understandable, we can call the cofactors “tools”, and the protein part of the enzyme a “master” who uses these tools for more efficient work. In this case, the master and the tools work harmoniously to achieve the best result!

The precursors of many coenzymes are vitamins, which is why we need a balanced diet to constantly maintain vitamin status at the proper level. Thus, one of the most important coenzymes - NAD + (nicotinamide adenine dinucleotide) - is obtained from niacin (B3). If niacin is absent or deficient in the diet, certain enzymes (such as dehydrogenase) will not be able to work effectively in the body. Such a person will develop pellagra, a disease caused by vitamin B3 deficiency.

Where are human hormones produced?

Hormones are secreted by endocrine glands, and some are secreted by tissues, certain organ cells.

Hypothalamus.

It is the key organ that directs all other glands and the release of peripheral hormones and works in close connection with the pituitary gland. The hypothalamus itself secretes releasing hormones. They give the command to the pituitary gland to launch or suppress the synthesis of certain hormones - tropins (tropic hormones). These pituitary hormones already control the work of the glands in the periphery - the thyroid gland, adrenal glands, genitals, etc.

Pituitary.

It also releases some hormones that directly regulate the functioning of tissues and cells - oxytocin, somatotropin, prolactin, vasopressin.

Epiphysis (pineal body).

This small gland is located next to the pituitary gland and hypothalamus. Today, the pineal gland is also classified as an endocrine gland; it secretes melatonin, a substance that regulates people’s sleep and activity cycles.

Thyroid.

It secretes the hormones T3 and T4, as well as thyrocalcitonin. They regulate metabolism, body temperature, protein synthesis and breakdown, weight gain and loss, as well as calcium metabolism.

Parathyroid glands.

Parathyroid hormone is released. It is needed to regulate the level of mineral salts in tissues, which help strengthen the skeleton and work the muscles.

Thymus.

It secretes the hormone thymosin, as well as thymopoietin and thymosterol, which help the immune system function and stimulate the formation and maturation of T-category lymphocytes.

Pancreas.

Its main role is the release of the hormone insulin, as well as its antagonist, glucagon. They help regulate the level of carbohydrate metabolism (or, more simply, the concentration of sugar in the blood and tissues, cells).

Adrenal glands.

These are complex endocrine organs that secrete three groups of hormones. Some of them are synthesized in the medulla - the well-known adrenaline and the lesser known norepinephrine. The cortex of these same modest-sized organs secretes steroid hormones. Among the most famous are cortisol (responsible for stress), aldosterone (responsible for the excretion or retention of water). The adrenal glands also secrete sex hormones (although not in the same volume as the genitals).

Insufficiency of the enzyme system - genetics or the result of poor nutrition

The enzyme system can suffer as a result of hereditary pathologies, and can also be modified after birth. There are 2 classes of enzymes in the body - metabolic and digestive. 2700 enzymes are synthesized inside us and each of them has a special role!

Disorders associated with metabolic enzyme abnormalities include widespread clinical manifestations and can involve virtually any organ system: lymphatic, cardiovascular, nervous, endocrine, urinary, hepatic, and reproductive. As a rule, such disorders arise as a result of genetic mutations and are inherited in a recessive manner. For example:

• Deficiency of enzymes of porphyrin metabolism

  is a group of diseases that are based on disturbances in the heme biosynthesis cycle. Each enzymatic reaction in the heme biosynthesis cycle is catalyzed by a separate enzyme, and the deficiency of any (except the first) of the enzymes that catalyze a certain stage of heme biosynthesis can lead to the development of the clinical stage of a certain form of porphyria. As a result, either the nervous system or the skin is damaged.

• Damage to the nervous system

  also occurs when arylsulfatase activity decreases, resulting in disruption of myelin metabolism and accumulation of cerebroside sulfatide in the myelin sheaths within the central and peripheral nervous system - metachromatic leukodystrophy.

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• Galactosemia

  refers to hereditary diseases of carbohydrate metabolism and combines several genetic forms. The disease is based on a deficiency of one of the three enzymes involved in galactose metabolism: galactose-1-phosphate uridyltransferase (GALT), galactokinase (GALA) and uridine diphosphate (UDP)-galactose-4-epimirase (GALE).

• Fructosuria

  – increased fructose content in urine as a result of deficiency of the enzyme fructokinase.

For people with such characteristics, only symptomatic therapy is indicated, which cannot be said about problems with the digestive enzyme system.

Proteolytic enzymes

Enzymes are an integral part of any biochemical reaction that occurs in the body. The very meaning of the word enzymes is usually identified with the process of digesting food in the gastrointestinal tract. Enzymes also provide redox processes, energy storage, oxygen absorption, and also carry out certain metabolic processes inside each cell and have a protein structure.

With age, our body produces fewer and fewer enzymes, the synthesis of which can also be affected by harmful environmental factors, infections, and deficiency conditions (lack of protein, microelements, vitamins in food). If incomplete digestion of protein molecules occurs in the intestines, then their fragments are absorbed into the blood, disrupting not only metabolic processes, but also negatively affecting the immune system.

Proteolytic enzymes play a key role in metabolism and especially in such important body functions as:

• immunological reactions,
• vascular tone,
• intercellular interaction,
• blood clotting,
• fibrinolysis, etc...

In recent years, enzyme and multienzyme products have been widely used in medical practice, which are used topically and for the treatment of diseases of the digestive system. The therapeutic effect of proteolytic enzymes during resorptive action has not been sufficiently studied, since for a long time it was believed that these enzymes act mainly in the digestive canal.

One of the main questions of systemic enzyme therapy: what is the degree of resorption (absorption) of proteolytic enzymes in the intestine and their effect on various organs and systems of the body?

Some of the enzymes that have not passed the intestinal barrier are included in the digestion process, regulating the function of the stomach, intestines, liver, pancreas, and other organs. A certain amount of proteolytic enzymes contained in NSP enzyme products circulating in the blood can enter the intestines through the enteropancreatic circulation.

In complex therapy of various diseases, proteolytic enzymes are successfully used, which leads to a reduction in treatment time. Their effectiveness is due to the expressed:

• anti-inflammatory,
• decongestant,
• immunomodulatory,
• fibrinolytic,
• necrolytic,
• painkillers,
• hypolipidemic,
• antioxidant effect.

Enzymes improve regional microcirculation.

Breakdown and absorption of proteins

Protease Plus enhances protein fermentation processes in all structures and tissues of the body, including food digestion. The composition includes not only a highly active protease enzyme, but also a micromineral complex obtained from plant sources.

Immunity

Protease Plus activates macrophages and immune killer cells, which justifies the use of the complex in immunodeficiency conditions and oncology.

Enzyme products do not cause any significant side effects and can be used in high doses for a long time at all stages of the development of malignant neoplasms - from prevention, to supporting the body during chemotherapy or radiation, as well as alleviating the condition of patients in the terminal stage.

With enzyme therapy:

• Liver function is normalized;
• Fibrinolysis improves;
• Microcirculation improves;
• Antitumor immunity is activated;
• The concentration of cytokines is normalized;
• The effectiveness of radiation and chemotherapy increases, while simultaneously reducing their negative impact;
• The number of pathological autoimmune complexes is reduced by destroying them.

Products for systemic enzyme therapy exhibit a therapeutic effect in atherosclerosis, elastase activity increases, and the structure of collagen and elastic structures is restored. The anti-atherosclerotic effect of enzymes is associated with the effect on metabolism in the connective tissue of arterial vessels. Systemic enzyme therapy prevents metabolic damage to the myocardium and prevents the formation of fibrosis in myocarditis.

How do digestive enzymes work?

Absorption of nutrients occurs with adequate levels of digestive enzymes. As we know, the digestion process begins in the oral cavity - this is where the first activity of the enzymes amylase and maltase, which break down carbohydrates and are synthesized by the salivary glands, appears. But the action of enzymes does not end here; they continue to be released in the stomach, pancreas, liver, and small intestine. Normally, the entire system works smoothly and the gastrointestinal tract performs its function 100% without taking exogenous enzyme supplements. However, if you are experiencing digestive problems such as acid reflux, irritable bowel syndrome, inflammatory bowel disease, or malabsorption, then supplementing with digestive enzymes may help you alleviate these conditions.

Intolerance to certain types of foods can also be associated with enzyme deficiency. For example, with lactase deficiency, intolerance to dairy products will occur, pain and rumbling in the abdomen, flatulence, and diarrhea with the release of watery, foamy feces will appear.

Today, more and more people are taking digestive enzymes, especially those who have certain health problems - gastrointestinal diseases, which include ulcerative colitis or Crohn's disease, hypochlorhydria (too low stomach acid levels) or pancreatic insufficiency (too low pancreatic production). enzymes).

Digestive enzyme supplements are a broad class that includes pancreatic enzymes, plant-derived enzymes, and fungal-derived enzymes. Such supplements can help relieve gastrointestinal problems by helping to break down food properly. They help convert macronutrients, that is, larger food molecules (proteins, fats and carbohydrates) into easily digestible particles (amino acids, fatty acids, cholesterol, simple sugars and nucleic acids) that the body can later use for normal functioning and energy. The human body produces special digestive enzymes that facilitate the absorption of various types of food.

Digestive enzymes are divided into three classes

:

1. proteolytic enzymes necessary for the digestion of proteins;
2. lipases necessary for the digestion of fats;
3. Amylases, necessary for the digestion of carbohydrates.

Benefits of Digestive Enzymes

:

• Prevents malabsorption of nutrients (malabsorption syndrome). This syndrome is observed both due to low levels of stomach acid and enzymatic deficiency.
• Reduces symptoms of acid reflux and irritable bowel syndrome (IBS).
• Minimize symptoms such as bloating, gas, abdominal pain, diarrhea and fatigue.
• Helps treat leaky gut by relieving stress on the gastrointestinal tract.
• Preventing symptoms of food intolerance, for example, by breaking down certain proteins and sugars – gluten, casein and lactose.

Exocrine insufficiency

Unfortunately, today more and more people are suffering from sectoral failure. And if earlier the age category began at about 50 years old, today the bar has moved much lower, and younger people suffer from it.

Exocrine insufficiency is a lack of enzymes (secrets), due to which the breakdown of all useful substances in the body occurs. This happens because over time, under the strong influence of certain factors, the number of cells in the gland that produce this very important secretion decreases.

What digestive enzymes are produced in the human body

• trypsin, chymotrypsin, erypsin, elastase, transamidinase, carboxypeptidase, collagenase - proteolytic function

  - participate in the breakdown and digestion of proteins, resulting in the formation of amino acids;

• ribonuclease, deoxyribonuclease - nucleolytic function

  - break down nucleic acids into nucleotides;

• amylase, maltase, lactase, glucosidase, fructofuronidase - glycolytic function

  - participate in the breakdown and digestion of carbohydrates, resulting in the formation of sugars;

• lipase, phospholipase, cholesterol esterase, lipoprotein lipase, esterase - lipolytic function

  - participate in the breakdown and digestion of fats, resulting in the formation of fatty acids and glycerol.

Enzymes require an alkaline reaction to function. This is why we increasingly hear about alkalizing the body with the help of plant products.

Yes, yes, vegetables contribute to the normal function of not only gastric, but also pancreatic juice!

The pancreas is an enzyme station

The pancreas plays an important role in both digestion and absorption of nutrients, as it secretes pancreatic enzymes that facilitate the breakdown of food into smaller molecules and promote the absorption of proteins, fats, carbohydrates, vitamins, and minerals. It is the main enzyme station of our body.

The health of the pancreas depends on the condition of the body as a whole - its work can deteriorate against the background of pathological conditions of the liver, gall bladder, intestines, and stomach.

What factors influence the state of the enzyme station?

1. Inflammatory processes in the gastrointestinal tract - pancreatitis, gastritis, enteritis.
2. The presence of stones in the gall bladder, resulting in a violation of the outflow of pancreatic secretions.
3. Low stomach acidity, which reduces the production of digestive enzymes and hydrochloric acid.
4. Cystic fibrosis.
5. Infections lead to excessive release of pancreatic enzymes, which begin to digest the pancreas's own.
6. Dysbacteriosis - pathogenic microorganisms damage the enzymes of intestinal juice. The amount of lactase, maltase and trehalase decreases.
7. Avitaminosis (lack of vitamins B, C, E, PP, nicotinic acid).
8. Overeating, as a result of which the gastrointestinal tract cannot cope and cannot produce enzymes in the required volume.
9. Poor nutrition and strict diets.
10. Parasitosis and helminthic infestations.
11. Autoimmune disorders.
12. Frequent drinking of alcohol.
13. Surgical operations on the gastrointestinal tract.
14. Long-term use of medications that destroy pancreatic cells.

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Here are some examples of foods to include in your meals to support pancreatic health:

• Foods rich in antioxidants include raw vegetables, berries and unsweetened fruits.
• Healthy fats – coconut, olive, avocado, ghee, MCT;
• Fermented foods.
• Quality protein – wild fish, free-range eggs, free-range meat.
• Seeds and nuts (preferably pre-soaked);
• Sprouts.
• Herbs and spices.

Causes

There are two types of enzyme deficiency: congenital and acquired. Congenital deficiency develops against the background of a genetic defect that disrupts or blocks the production of pancreatic enzymes. The acquired form of the disease most often occurs as a result of pancreatic pathologies (for example, pancreatitis) or poor nutrition.

Enzyme deficiency also occurs:

• primary and secondary;
• relative and absolute.

In 70% of cases, the cause of exocrine dysfunction is inflammation in the pancreas tissues

Primary failure occurs against the background of pathological processes in the parenchyma of the gland, leading to inhibition of its exocrine function. And secondary failure has a slightly different development mechanism. With this pathology, the pancreas produces enzymes in sufficient quantities, but once they penetrate the small intestine, for some reason they are not activated.

If we talk specifically about what factors can trigger the development of this pathology, we can highlight the following:

Tablets for the pancreas

• Shwachman and Johanson-Blizzard syndrome;
• chronic pancreatitis;
• pancreatic cancer;
• cystic fibrosis;
• obesity, in which fat cells begin to be deposited in the tissues of the gland;
• surgical interventions;
• pancreatic hypoplasia.

Also, the development of enzyme deficiency can occur against the background of:

• pancreatic atrophy or fibrosis;
• pancreatic cirrhosis;
• pancreatic necrosis;
• deposits of stony elements in the pancreatic ducts.

Stones in the pancreatic ducts prevent the normal excretion of pancreatic juice from the gland, thereby reducing the concentration of enzymes entering the intestines, which disrupts the functioning of the gastrointestinal tract

As medical practice shows, enzyme deficiency is most often a consequence of pancreatitis (obstructive, alcoholic, calculous and non-calculous), since during its development pathological processes are activated in the pancreatic tissues, resulting in atrophy and fibrosis of the gland. However, these conditions can also provoke other diseases, such as atherosclerosis and diabetes.

Naturally, the patient’s diet plays an important role in the development of enzyme deficiency. The pancreas activates the synthesis of enzymes the moment food enters the esophagus. If there is too much of it or it has a heavy composition, the gland does not have time to produce the required amount of enzymes for its digestion, as a result of which it begins to experience severe stress, leading to a disruption of its functionality. It is for this reason that doctors strongly recommend that all people monitor their diet, eating only healthy foods and avoiding overeating.

Secondary failure most often develops in the following cases:

• for various lesions of the small intestine;
• gastrinoma;
• insufficient synthesis of enterokinase;
• protein-energy deficiency;
• pathologies of the gallbladder, liver and bile ducts.

The absolute form of the pathology is characterized by inhibition of exocrine functions and bicarbonate synthesis as a result of degeneration of the gland parenchyma. Relative insufficiency is a consequence of obstruction of the lumen of the pancreatic ducts, as a result of which the process of entry of pancreatic juice into the small intestine is disrupted. This usually happens when stony deposits, tumors or scars appear in the gland ducts.

Necrosis of the pancreas, causing the development of enzyme deficiency

Top 15 Enzyme Rich Foods

1. a pineapple;
2. papaya;
3. kiwi;
4. kefir;
5. yogurt;
6. bananas;
7. mango;
8. miso;
9. pace;
10. homemade sauerkraut;
11. kimchi;
12. avocado;
13. bee pollen;
14. Apple vinegar;
15. raw honey

What foods harm the enzyme station?

• Alcohol.
• Fresh sweet fruit.
• Fried, smoked, salted.
• Trans fats and fast food.
• Processed and refined foods.

Symptoms of enzyme deficiency

• Flatulence.
• Nausea and vomiting.
• Foul-smelling diarrhea - increased frequency of bowel movements, feces with excess fats, which are poorly flushed from the toilet, become gray in color and have a putrid stench.
• Dehydration of the body.
• General weakness.
• Bloating and gas.
• Feeling of heaviness in the stomach.
• Painful sensations in the lower abdomen, in the area of ​​the umbilical ring. As a rule, they give to the sides.
• Rumbling and seething in the stomach.
• Decreased appetite and weight loss.
• Dryness and grayness of the skin.

In children, the signs of deficiency will be similar. You can notice a change in their behavior - lethargy, lack of appetite, but at the same time frequent bowel movements. Such symptoms can be confused with an intestinal infection; laboratory diagnostics will show the final result.

Symptoms of reactive pancreatitis

The first symptoms of reactive pancreatitis appear quite quickly. Sometimes after the action of the provoking factor, only a few hours can pass - and the disease will already make itself felt. The most characteristic signs of reactive pancreatitis include1:

• pain in the upper abdomen, radiating to the ribs and shoulder blades and intensifying after eating;
• increased gas formation;
• nausea, vomiting with traces of bile;
• slight increase in body temperature;
• decrease in blood pressure.

If signs of reactive pancreatitis appear, you should consult a specialist to conduct a professional diagnosis and begin treatment at an early stage of the disease.

Tests to assess enzyme levels

Laboratory diagnosis of enzyme deficiency includes

:

1. General clinical blood test.
2. Blood test for sugar, vitamins and fatty acids,
3. Biochemical blood test to determine the level of pancreatic and stomach enzymes: alpha-amylase and pancreatic amylase, lipase, as well as pepsinogen I and pepsinogen II, pepsin.
4. Coprogram.
5. Elastase immunoassay test (determining the level of elastase-1 in feces).

Treatment of enzyme deficiency

In the treatment of enzyme deficiency, a huge role is played by the diet and rules of nutrition - providing the body with the necessary amount of nutrients, maintaining normal blood sugar levels, sparing the pancreas and eliminating triggers. To do this, you must follow several important principles:

• It is recommended to eat in small portions (100–300 g).
• Eating easily digestible protein foods.
• Gentle temperature regime - cold and hot dishes irritate the pancreas, it is necessary to eat warm food.
• Exclusion from the menu of fried and spicy foods: boiling, steaming or baking is recommended.
• Chewing thoroughly, since with enzyme deficiency it is very difficult for the body to digest large pieces of food.
• Limited salt intake.
• Do not drink immediately after meals, as this may reduce the concentration of gastric juice and interfere with digestion.

Types of deficiency

Today there are four types of functional pancreatic insufficiency. Each of these types has its own characteristics, ranging from the causes of its appearance to symptoms and treatment. So, they distinguish:

1. Exocrine insufficiency
2. Exocrine insufficiency
3. Enzyme deficiency
4. Endocrine insufficiency

As mentioned above, each of them has its own characteristics. Therefore, in order to fully understand what the differences are and whether there are similarities in the manifestation of symptoms, it is necessary to get to know each one better. Glandular insufficiency is not a very pleasant circumstance. But in order to establish what kind of deficiency is taking place, it is necessary to consult with a doctor who, based on the symptoms, will make an accurate diagnosis and prescribe the necessary treatment.

When is enzyme supplementation indicated?

A person who does not have digestive problems and does not experience pathological symptoms simply does not need to take enzymes, since the body must produce enough of them on its own. But in other cases, additional enzymes are still necessary:

• Chronic pancreatitis.
• Other chronic, autoimmune diseases.
• Pancreas cancer.
• Tumors of the pancreas or duodenum.
• High level of inflammation.
• High triglyceride levels.
• Parasitic infections.
• Alcoholism.

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• Recent surgery to remove pancreas.
• Age-related enzyme deficiency.
• The presence of heartburn, bloating, increased gas formation, malabsorption, constipation and diarrhea.
• Reduced immunity.
• If you can't gain weight for a long time.
• After poisoning.
• During intense physical activity.
• Elderly age.

We're now seeing more research into the gut-brain connection - which could improve the effectiveness of treatment for children with autism spectrum disorder (ASD). One such study showed that in a group of children taking digestive enzymes for 3 months, there was a significant improvement in emotional reactions, a decrease in autism scores, normalization of behavior and manifestations of pathological gastrointestinal symptoms.

Introduction

Digestion of food is accompanied by complex physiological processes.
This is especially true for the process of regulation of the production and activation of pancreatic enzymes. The causal chain starts when acid leaves the stomach and enters the duodenum (duodenum), which leads to the formation of secretin in it. Secretin stimulates the pancreas' production of pancreatic juice and bicarbonates. This leads to alkalization of the duodenal environment to a pH level that is optimal for the secretion of pancreatic enzymes. Enzyme secretion is stimulated by pre-fermented nutrients such as peptones, amino acids and fatty acids, which lead to the release of cholecystokinin (CCK) from the duodenum. Cholecystokinin induces contraction of the gallbladder and the release of acetylcholine from intrapancreatic nerve fibers, which in turn stimulates the secretion of pancreatic enzymes. CCK itself does not appear to have a direct effect on human lifespan. To avoid organ autolysis, most pancreatic enzymes are synthesized as inactive precursors - the so-called. zymogens or proenzymes (trypsinogen, chymotrypsinogen, proelastase, etc.), which are then additionally enclosed in organelles (zymogen granules). The enzyme amylase has spontaneous activity. Lipase has an intermediate status because it is synthesized as an active enzyme, but its lipolytic activity depends on the activation of a cofactor (colipase). Exocrine enzymes are released by acinar cells of the pancreas through a complex mechanism (fusion of the membranes of zymogen granules with the apical membranes of acinar cells). The process of activation of proenzymes begins in the duodenum with the release of enterokinase from the mucous membrane of the upper parts of the small intestine into the intestinal lumen. This leads to the cleavage of the peptide (trypsinogen-activating peptide) in trypsinogen, followed by the formation of active trypsin as a result of a complex process called folding. The active trypsin thus formed is capable of activating other proenzymes.

The mechanisms of “switching off” the secretion function of exocrine pancreatic enzymes have only been partially studied. It is believed that when the contents of the gastrointestinal tract come into contact with the ileum, hormones (for example, peptide YY, or tyrosine-tyrosine peptide) are released, which suppress the secretion of pancreatic enzymes and at the same time reduce appetite [1].

Various pancreatic diseases can be accompanied by disruption of these very complex processes. This review discusses the pathophysiology of pancreatic failure, its diagnosis and treatment.

Etiology of exocrine pancreatic insufficiency

The most common cause of exocrine pancreatic insufficiency in adults is chronic pancreatitis, followed by pancreatic cancer, pancreatic resection, and impaired healing after necrotizing acute pancreatitis with loss of pancreatic tissue. In children, the most common cause is cystic fibrosis. Thanks to successful pulmonary therapy, many patients with cystic fibrosis reach adulthood with pancreatic failure, which still requires treatment. Exocrine insufficiency is also very common in diabetes mellitus. However, some controversy arises in this case, in particular due to the difficulty in explaining the presence of functionally significant exocrine insufficiency in patients with type 2 diabetes, who are usually overweight.

In addition to organic ones, there are functional causes of exocrine pancreatic insufficiency. These include, among others, gluten-sensitive enteropathy, Crohn's disease with significant ileal involvement, and postcibal asynchrony of the pancreas. After resection of the pancreas, the cause of failure can be both functional (i.e., postoperative) and organic factors (for example, a chronically altered small remnant of pancreatic tissue). After a gastrectomy or even a partial gastrectomy or after a gastroenterostomy (for obesity that interferes with the normal functioning of the body, or stenosis of the duodenum due to a tumor), stomach contents may either enter the duodenum too quickly or not enter it at all, resulting in the release of too small quantities CCK and secretin.

In this case, postcibal asynchrony of the pancreas is the cause of functional digestive insufficiency. There have been no prospective studies demonstrating the benefit of using pancreatic enzyme-containing medications after this type of surgery. However, given the pathophysiological factors described above and our own clinical experience, we recommend treatment with pancreatic enzymes [2].

Chronic pancreatitis

In industrialized countries, 70 to 80% of cases of chronic pancreatitis (CP) are thought to be alcohol-induced. In 20 to 30% of cases, the underlying cause cannot be determined. In some rare cases, the causes are a divided pancreas, hyperparathyroidism and severe hypertriglyceridemia. Approximately 30–35% of patients have genetic disorders, such as mutations in the CFTR (cystic fibrosis transmembrane conductance regulator), SPINK (Kazal-type serine protease inhibitor) or chymotrypsin C gene [3]. In less than 1% of cases, hereditary pancreatitis occurs - a disease with an autosomal dominant type of inheritance. In 70–80% of such cases, patients have mutations in cationic trypsinogen [4].

However, many patients simultaneously have several risk factors, for example, the use of low-alcohol drinks in combination with a genetic risk factor or nicotine addiction, as a result of which the classification of causes into only one category, for example, the category of “chronic alcohol-associated pancreatitis”, does not make sense . It would be more accurate to use the term “chronic pancreatitis” and list the existing risk factors.

With CP, it is impossible to predict at what point in time indigestion will occur. The likelihood of developing exocrine insufficiency increases over time. After 10 years, more than half of patients with chronic alcohol-associated pancreatitis will develop exocrine insufficiency; after 20 years it will be observed in almost all such patients [5]. In patients with pancreatitis not associated with alcohol consumption, the progression of the condition to exocrine insufficiency is slower [6].

The pancreas has large reserves. According to EP DiMagno et al., steatorrhea develops only if more than 90% of the organ tissue is destroyed. Steatorrhea is accompanied by voluminous, yellowish, foul-smelling stools with a total daily fecal weight significantly exceeding 200 g and the excretion of more than 7 g of fat in feces per day [7]. Carbohydrates and proteins are partially broken down by enzymes of saliva (amylase), stomach (pepsin) and the mucous membrane of the small intestine (peptidases, saccharidases). The breakdown of fats, however, largely depends on the enzyme pancreatic lipase.

Pancreatic failure after severe acute pancreatitis and pancreatic cancer

Exocrine insufficiency may occur after severe acute pancreatitis or after pancreatic surgery. The reason in this case is the absence or insufficient amount of exocrine tissue. After resection of the pancreas, hypertrophy of the organ remnants is usually not observed. However, in isolated cases, for example in patients with biliary pancreatitis, pancreatic function may improve within 12–24 months after the episode, which cannot be said about patients with CP, in whom the function of this organ progressively worsens [5]. Pancreatic failure is also common in patients with pancreatic cancer and is caused by obstruction of the pancreatic ducts by the tumor, and is also a factor explaining weight loss in these patients.

Diagnosis of pancreatic failure

A variety of methods are used to confirm RV failure, based on a wide variety of underlying testing principles. The fact that there is such a wide variety of testing methods suggests that none of them is absolutely reliable.

Tests confirming the presence of exocrine pancreatic insufficiency:

• CCK-secretin test;
• fecal elastase test;
• mixed triglyceride breath test;
• fecal fat test;
• magnetic resonance cholangiography (MRC) after secretin stimulation;
• visual inspection of stool.

The CCK-secretin test, the most sensitive direct test of pancreatic function, is no longer used in Germany because CCK (formerly known as pancreozymin) and its synthetic analog ceruletide are no longer available for human use in that country. Accurate quantitative diagnosis of the presence of pancreatogenic steatorrhea requires measurement of the amount of fat excreted in the stool based on a stool sample collected over three days after a standardized diet of known fat content (pathological level >7 g/day). For obvious reasons, this method is rarely used. Currently, pancreatic failure is usually confirmed using a fecal elastase test.

However, a meta-analysis showed that this test gives reliable results only in cases of moderately expressed or insufficiently expressed pancreas [8]. In patients with diarrhea of ​​various etiologies, the content of elastase in feces is often reduced to false-positive values; perhaps this problem could be solved by using special containers for collecting feces [9]. The mixed triglyceride breath test, which is an indirect method, has also not yet been well studied for sensitivity. For this test, triglycerides are labeled with the stable isotope 13C. In the presence of a sufficient amount of lipase, 13C-labeled CO2 is formed, the volume of which in exhaled air can be measured [10]. Visual assessment of increased fecal fat excretion is at best only possible in patients with severe steatorrhea [11]. Indirect tests for pancreatic function, such as the fluorescein dilaurate test and chymotrypsin kinetic test, are no longer used in Germany. Determination of serum lipase or amylase activity does not allow drawing conclusions about pancreatic function [12]. The MRX method after secretin stimulation has not been evaluated in large-scale comparative studies for the sensitivity of detecting pancreatic failure.

Whether endoscopic secretin testing will improve diagnostic results remains to be seen [13].

Chronic pancreatitis can be diagnosed using imaging techniques such as ultrasonography, endoscopic echography, computed tomography and magnetic resonance imaging. However, due to the lack of a close relationship between the structure and the remaining function of the organ [14], in patients with morphologically extensive CP, accompanied by dilation and calcification of the ducts, secretory function may in fact be maintained at a sufficient level. However, loss of exocrine function can be suspected in almost all patients with morphologically evident organ destruction. Conversely, in the case of minor morphological changes, one can suspect the absence or, in the worst case, the presence of only borderline exocrine insufficiency. The literature also expresses different opinions about the significance of the concomitant excessive development of bacterial microflora in the intestine [15].

Treatment of exocrine pancreatic insufficiency

Available enzyme preparations. The most widely used preparations are those based on porcine pancreatin [16]. A review of various drugs and their effectiveness was published by Löhr et al. [17].

The following requirements are imposed on the pancreatin preparation: it must:

1. Contains highly active lipase.
2. Protect lipase from destruction by stomach acid.
3. Mix with stomach contents
4. Leave the stomach along with the contents.
5. Rapidly release pancreatin from the protective enteric membrane in the duodenum.

Because porcine pancreatin lipase is destroyed by proteases and acids, it is necessary that pancreatin be protected from the effects of stomach acid when administered to patients who retain the ability to produce this acid. Other important factors in the effectiveness of an enzyme preparation are the particle size (for smooth gastric emptying) and the rate of release of enzymes into the duodenum. The most optimal particle size is considered to be <2 mm in diameter, because it is assumed that particles of this size can be in the stomach simultaneously with solid food [18]. The enzymes should be released within 30 minutes. Reduced buffering of gastric acid as a result of decreased bicarbonate secretion in CP slows down the release time of enzymes from enteric-coated particles and thus interferes with digestion. This may further explain why steatorrhea is usually not completely curable even with high-dose pancreatin replacement therapy.

In one study, in which, due to the small number of cases, only drug equivalence could be assessed, we found that enteric-coated mini-micropellets (diameter 90% <1.25 mm) performed equally well when compared to minipellets (diameter >70% diameter). from >1.25 to 2.0 mm) improved fat digestion [19]. Pancreatin preparations taken orally, which are not enteric coated, are broken down not only by the action of acid and pepsin, but also after release into the duodenum by the action of the enzymes themselves, especially lipase, which is of such great importance [20].

The results of published studies of drugs based on fungal lipase (rhizoplase isolated from the fungi Rhizopus oryzae) are far from satisfactory. From a theoretical point of view, acid-stable lipase produced by microorganisms should be an ideal agent [21]. However, this drug has not yet been approved for human use and has not demonstrated efficacy equivalent to pork pancreatin in the digestion of fats. There are still no clinical studies comparing different enteric-coated micropellets, microspheres and mini-tablets containing porcine pancreas extract. Therefore, claims that one brand of drug are equally or even more effective than another brand of drug are still not possible. Nevertheless, we quite successfully treat many patients with documented exocrine pancreatic insufficiency with enteric-coated mini-tablets (Pancreatin, Ermital®, Ermytal® in Russia**). Studies have shown that this brand of enzymes are rapidly released when pH levels increase [22]. Thus, we are convinced that the drug of this brand has the same effectiveness compared to competitive drugs.

Indications for enzyme therapy and dosage

The indication for therapy with pancreatic enzymes is exocrine insufficiency. As mentioned, deficiency is difficult to diagnose and test results may be unreliable. For this reason, the criteria on the basis of which treatment is prescribed are that the patient not only has a disease leading to exocrine insufficiency, but also symptoms such as flatulence, diarrhea, steatorrhea and/or weight loss. The same criteria are also taken into account in patients with functional insufficiency of the pancreas, such as postcibal asynchrony after gastric/prostate surgery, or gluten-sensitive enteropathy.

The dosage of pancreatic enzymes is selected individually. The optimal initial dose is from 25 thousand to 40 thousand IU of lipase per main meal. The dosage for taking with light meals or snacks depends on the volume of the latter, but in any case should be at least 10 thousand IU. In order for pancreatin preparations to mix well with food in the stomach, they should be taken not before, but during or immediately after meals [23]. If treatment does not bring positive results, the dose can be increased. If treatment results remain unsatisfactory, treatment with proton pump inhibitors can be prescribed simultaneously. Pancreatic enzyme preparations should also be prescribed to patients with severe exocrine insufficiency who are on a polymer diet (the so-called cosmonaut/astronaut diet) [24].

In exceptional cases, exocrine insufficiency may occur even if the results of pancreatic function tests do not reveal any abnormalities or borderline pathologies. Then you can prescribe a course of enzyme treatment lasting approximately 14 days. In the absence of sustained improvement in symptoms, the cause of the disorder is most likely not exocrine insufficiency and further treatment with pancreatic enzymes should not be continued.

Treatment of pain syndrome

Studies in rodents have shown that proteases in the duodenum inhibit the secretion of pancreatic enzymes through a negative feedback mechanism. Proteases are capable of destroying peptides that release CCK. However, in a study involving healthy volunteers, we were able to demonstrate that the potential inhibitory effect of proteases on enzyme secretion was counteracted by the high protein content of porcine pancreas extracts. Proteins stimulate the secretion of pancreatic enzymes through the release of CCK. In a prospective randomized study, we were able to show that porcine pancreas extracts do not have a positive effect on the treatment of pain in patients with CP [25].

Side effects

When treating patients with cystic fibrosis with high doses of pancreatin, a side effect such as inflammatory stenosis of the colon has been reported [26]. It is not known what caused these stenoses: components of the enteric coating or a high concentration of digestive enzymes?

Key messages

Mini micropellets (diameter <1.25 mm), micropellets (diameter <1.25 mm) and mini-tablets (diameter = 2 mm) are equally effective in the treatment of exocrine pancreatic insufficiency. There are no double-blind comparative studies showing that one brand of drug is more effective than other brands. We also recommend reading our recently published guide [27] for additional information.

Statement 1

If there is clinical doubt that symptoms persist due to failure of pancreatic enzyme treatment, fecal fat excretion or pancreatic function tests that assess food digestion during treatment, such as 13C-labeled lipids, should be performed (LE: 1b/2b , recommendation grade B, agreement).

Statement 2

Pancreatin should be taken with food (level of evidence 1b, grade of recommendation A, strong agreement).

Statement 3

The activity of the enzymes used from pancreatic extracts should be high enough to ensure the digestion of food (grade of recommendation A, full agreement).

Statement 4

The dose of enzyme preparations from pancreatic extracts is selected depending on the activity of lipase. Treatment should begin with a dose of 20 to 40 thousand units (valid EUR pharma.) per main meal; When eating snacks, 10K (up to 20K) units of lipase may be sufficient (Evidence Level 1b, Recommendation Grade B, Strong Agreement).

Statement 5

If there is no effectiveness, the dose should be doubled or tripled (level of evidence 5, grade of recommendation B, strong agreement).

Statement 6

If enzyme preparations from pancreatic extracts are not effective, they should be combined with a proton pump inhibitor (evidence level 2b, grade of recommendation B, full agreement).

Statement 7

Almost all pancreatic enzyme preparations available in Germany contain extracts of porcine pancreas. They can also be used as medicinal products in patients who do not consume pork products for religious or ethical reasons (level of evidence 5, grade of recommendation C, strong agreement).

Statement 8

Patients with CP should avoid drinking ethyl alcohol (level of evidence 2b, grade of recommendation A, full agreement).

Statement 9

If necessary, vitamin and mineral deficiencies should be supplemented (level of evidence 2b, grade of recommendation A, agreement).

Types of Enzyme Supplements

Pancreatic enzyme supplements are obtained from both plant and animal sources—papaya, pineapple, and livestock.

Most options contain pancreatin, which is a combination of all three groups of pancreatic enzymes.

Types of enzymes

:

1. Amylase is an enzyme that breaks down carbohydrates.
2. Lipase is an enzyme that promotes the breakdown of fats.
3. Protease and peptidase are enzymes that help break down proteins.
4. Papain - participates in the digestion of meat.
5. Alpha galctosidase is an enzyme that helps digest complex carbohydrates with a high gas-forming potential (legumes, grains, oilseeds, root vegetables).
6. Beta-glucanase - helps digest fiber from grains and yeast.
7. Beta-galactosidase (lactase) is an enzyme that catalyzes the breakdown of lactose.
8. Pectinase - breaks down pectins from fruits.
9. Phytase - breaks down phytic acid.
10. Invertase - breaks down sucrose.
11. Cellulase - breaks down plant fiber.

The choice of treatment regimen for enzyme deficiency is determined by the attending physician, since each case requires an individual, comprehensive approach.

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Much of the choice depends on

:

• Type of underlying disease.
• Nature of enzyme deficiency.
• Severity of pain.
• Laboratory test results.

Only taking into account all these factors can you choose adequate treatment and achieve a positive result.

Amylase test

Amylase is an enzyme that is responsible for the breakdown of carbohydrates. It, unlike lipase, is produced not only by the pancreas, but also by the salivary glands. In addition, some amount of the enzyme is produced in the skeletal muscles, intestines and ovaries. A blood test for amylase is prescribed to patients with acute or chronic pancreatitis, if pathology of the ovaries or salivary glands is suspected.

In patients over 18 years of age, the enzyme level should not exceed 53 U/l. The norm for children varies depending on their age. The level of pancreatic amylase is analyzed by the doctor taking into account the total amount of enzyme. In acute pancreatitis, in most cases there is a significant increase in the amount of pancreatic enzyme. Sometimes the increase in indicators is insignificant or they remain within normal limits. The test results do not reflect the degree of damage to the pancreas, so a comprehensive examination is performed to confirm the diagnosis and develop a treatment regimen. An increase in indicators can be caused not only by pancreatitis, but also by traumatic damage to the pancreas, its oncology, blockage of the pancreatic duct, rupture of an aortic aneurysm, perforated ulcer, peritonitis, intestinal obstruction and other pathologies.

In acute pancreatitis,
amylase levels usually rise before lipase levels
. The lipase concentration remains high longer. To obtain a complete picture, a study to determine the amount of these two enzymes is carried out simultaneously.