Clinical and functional characteristics of the state of the small intestine in hypolactasia

The dissertation is devoted to the clinical and functional assessment of the small intestinal state in patients with primary and secondary hypolactasia. The work aims to improve the treatment of patients with lactase deficiency by means of a comprehensive study of the digestive, absorptive, and motor-evacuation functions of the small intestine, as well as the metabolic processes and hormonal regulation involved. Particular attention is paid to the investigation of membrane and luminal carbohydrate digestion, the state of the intestinal biocenosis, and neuroendocrine factors in this pathology. On the basis of the data obtained, the combined use of lactase and pancreatin in the complex therapy of hypolactasia has been proposed and substantiated, with an assessment of clinical effectiveness based on short-term and long-term results.

Relevance of the problem. Lactase deficiency is the most common cause of the malabsorption syndrome. [39, 40, 91, 93]. As data from recent years have shown, more than 50 million adult residents of the United States poorly tolerate milk and dairy products because of intestinal lactase deficiency [427, 429]. According to published data, in Europe about 50% of the adult population cannot tolerate milk, while among the indigenous populations of Africa and America the frequency of adult lactase deficiency reaches 100% [33-35, 39, 40]. The overall prevalence of hypolactasia in Russia is approximately 16% [169, 216].

In recent years, considerable attention has been drawn to secondary hypolactasia, which can develop not only in intestinal diseases but also in lesions of other digestive organs [33, 39, 185, 440]. This is due to the fact that in these diseases significant changes occur in the small intestinal mucosa, leading to the development of secondary hypolactasia.

In the development of the malabsorption syndrome, great importance is attached to intestinal dysbiosis [95, 185, 186, 188, 189; 200, 216]; however, the relationship between changes in the intestinal microflora and lactase deficiency remains insufficiently studied. In recent years, an important role in the stimulation and coordination of digestion and absorption in the gastrointestinal tract has been attributed to gastrointestinal hormones and hormones of the endocrine glands [41, 46, 49, 52, 101, 169; 183, 222, 230]. At the same time, there is still insufficient information on the role of hormones in the impairment of hydrolysis and resorption of food substances in hypolactasia.

Previously, the basis for the treatment of lactase deficiency was considered to be an elimination diet excluding milk and dairy products, or the use of lactose-free or low-lactose products manufactured by the food industry [91, 216, 217, 341]. However, a lactose-free diet not only narrows the patient's diet but also, according to recent data, causes a deficiency of certain essential substances in the body, including calcium [39, 40, 159, 169, 216, 217]. Mineral metabolism is impaired to some extent in all patients with the malabsorption syndrome [354]. It is known that lactase hydrolysis enhances calcium absorption, even in vitamin D deficiency [354]. Therefore, in hypolactasia, a decrease in calcium absorption is possible, which may lead to a pathological decrease in bone mass. Studies have shown that women after the onset of menopause often develop osteoporosis, which is largely due to decreased intestinal calcium absorption [325, 326]. Recently, studies have appeared showing that in these women the level of lactase activity is significantly reduced, which leads to hypolactasia and thereby to impaired intestinal calcium absorption [326, 411]. A similar development of osteoporosis in elderly men is also associated by a number of authors with the development of hypolactasia [370]. Complete exclusion of lactose also leads to disruption of the intestinal biocenosis, since milk sugar is a nutrient substrate for lactic acid bacteria [36, 39, 169, 216, 217].

In this regard, the search for optimal therapeutic approaches for patients with primary and secondary hypolactasia remains a relevant problem.

Aim of the work: improvement of treatment for patients with lactase deficiency on the basis of comprehensive studies of the functional state of the small intestine.

Research objectives

1. Study of the frequency and features of the clinical course of primary and secondary hypolactasia.

2. Comprehensive assessment of the functional state of the small intestine in patients with primary and secondary lactase deficiency.

3. Study of the role of neuroendocrine factors in the impairment of the functional state of the small intestine in hypolactasia.

4. Clinical evaluation of the therapeutic effectiveness of combined lactase and pancreatin administration in patients with primary and secondary hypolactasia.

5. Study of the effect of therapy on the functional state of the small intestine based on short-term and long-term follow-up data.

Scientific novelty. As a result of the conducted research, for the first time a comparative assessment of the clinical course and the nature of digestive and absorptive function disorders of the small intestine has been performed in patients with primary and secondary hypolactasia. Features of disturbances in the metabolism of carbohydrates, proteins, lipids, and calcium in enteric lactase deficiency are described. The establishment of a relationship between changes in the qualitative and quantitative composition of the intestinal microflora and the type of hypolactasia is new. For the first time, neuroendocrine regulatory factors and their role in the impairment of the functional state of the small intestine in hypolactasia have been investigated. A clinical and pathogenetic substantiation of the combined use of lactase and pancreatin in patients with hypolactasia has been provided.

Practical significance of the work. The research results contribute to a deeper understanding of modern concepts of primary hypolactasia and the formation of secondary hypolactasia. The sequential use of loading tests with mono-, di-, and polysaccharides makes it possible to identify the nature of the disorder in the digestive-resorptive process in patients with primary and secondary hypolactasia. The use of lactase and pancreatin as part of complex therapy makes it possible to increase the effectiveness of treatment for patients with hypolactasia. To stabilize the clinical effect, it is recommended not only to prescribe courses of lactase and pancreatin during exacerbations of chronic diseases in patients with hypolactasia, but also to take them situationally when consuming any lactose-containing products.

Statements submitted for defense:

1. When assessing the functional state of the small intestine in patients with hypolactasia, a comprehensive study is necessary to identify the presence of partial disorders of digestion and absorption.

2. In the impairment of the functional state of the small intestine in patients with hypolactasia, hormonal factors play a significant role.

3. The inclusion of lactase and pancreatin in the complex therapy of patients with hypolactasia promotes clinical remission of the diseases, leads to the restoration of digestion and absorption in the small intestine, has a beneficial effect on the intestinal biocenosis, and on the metabolism of carbohydrates, proteins, lipids, and electrolytes.

Implementation in practice. The method of treating patients with hypolactasia has been implemented in the practice of the therapeutic and gastroenterological departments of City Clinical Hospital No. 8 named after I.B. Odnopozov in the city of Izhevsk.

Publications. Fourteen works have been published on the topic of the dissertation.

Approval of the work. The main provisions of the dissertation were reported and discussed at the 5th Slavyano-Baltic Scientific Forum "Saint Petersburg - Gastro 2003" (Saint Petersburg, 2003), the VII International Congress "Parenteral and Enteral Nutrition" (Moscow, October 22-24, 2003), at the scientific and practical conference dedicated to the 20th anniversary of the surgical service of City Clinical Hospital No. 8 named after I.B. Odnopozov (Izhevsk, 2004), at the Saint Petersburg Medical Assembly - 2004 "Doctor - Pharmacist - Patient" (Saint Petersburg, November 23-26, 2004), at the V Congress of the Scientific Society of Gastroenterologists of Russia, XXXII Session of the Central Research Institute of Gastroenterology (Moscow, February 3-6, 2005), the 13th scientific and practical conference "Achievements of Modern Gastroenterology" (Tomsk, September 22-23, 2005), at the visiting plenum of the Scientific Society of Gastroenterologists of Russia "Clinical and Pathogenetic Aspects of Gastrointestinal Dysbiosis in Digestive Diseases: Diagnosis, Treatment, and Prevention" (Tver, November 10-11, 2005), at the VI Congress of the Scientific Society of Gastroenterologists of Russia (Moscow, February 1-3, 2006), and the VII Congress of the Scientific Society of Gastroenterologists of Russia (Moscow, March 20-23, 2007).

Structure and scope of the dissertation. The dissertation is presented on 217 typewritten pages. The work consists of an introduction, five chapters of original research, a conclusion (summary with discussion of results), conclusions, recommendations for practical public health, and a bibliography. The text is illustrated with 35 tables, 18 figures, and 3 case history extracts. The bibliography includes 291 domestic and 151 foreign sources.