Impaired protein digestion in the stomach
The initial stage of proteolysis suffers in pepsin deficiency and hypoacid states caused by mucosal atrophy, gastritis, or peptic ulcer disease. Pyloric stenosis and functional dyspepsia in children are also risk factors.
What this leads to:
- Hydrolysis and swelling of protein molecules are inhibited, blocking enzyme access.
- Digestion of collagen and muscle fibers worsens.
- Motility and evacuation of chyme into the duodenum are impaired.
Intestinal phase and enzymatic deficiency
At the intestinal level, problems arise against the background of acute and chronic enteritis, malabsorption syndrome, or congenital pancreatic hypoplasia. The key link in pathogenesis is insufficiency of pancreatic proteases and enteropeptidase due to genetic mutations.
Mechanism of pathology development:
- Proteins are not broken down into final amino acids and dipeptides.
- Large oligo- and polypeptides accumulate in the intestinal lumen.
- These incomplete molecules are absorbed into the systemic bloodstream.
- Pronounced immune sensitization of the body develops.
Celiac disease: gluten-induced enteropathy
The disease is associated with impaired digestion of plant protein — gluten and gliadin, ingested with cereal crops. Normally, peptides are cleaved by brush border enzymes of the small intestine.
However, the resulting $\alpha$-gliadin peptide is resistant to hydrolysis by gastric, pancreatic, and intestinal enzymes. The immune system recognizes it as a foreign antigen, triggering a cascade of reactions that damage the epithelium and cause villous atrophy.
Clinical manifestations:
- Abdominal pain, nausea, vomiting, flatulence, and constipation.
- In adults, a latent course, chronic diarrhea, anemia, and chronic fatigue syndrome often predominate.
Creatorrhea: meat utilization disorders
The term kreatos (meat) and rhoia (flow) conceals a pathology in which an excess of undigested muscle and connective tissue fibers, as well as unhydrolyzed nitrogen-containing substances, is detected in the feces.
Main causes and symptoms:
- Decreased secretory function of the pancreas and deficiency of trypsin and chymotrypsin.
- Impaired protein hydrolysis and nutrient absorption.
- Clinical features include diarrhea, flatulence, weight loss, recurrent vomiting, and the development of malabsorption in severe cases.
Briefly: answers to topical questions
What histological changes in the small intestinal mucosa, in addition to villous atrophy, are characteristic of celiac disease?
In addition to villous atrophy, the following histological changes in the small intestinal mucosa are characteristic of celiac disease:
- Crypt hyperplasia: villous shortening is accompanied by elongation and widening of the crypts.
- Cellular infiltration: massive infiltration of the lamina propria with lymphocytes and plasma cells mixed with eosinophils.
- Increased number of intraepithelial lymphocytes.
- Enterocyte changes: microvilli lose regularity, are deformed and shortened.
- Widening of intercellular contacts, which is associated with epithelial barrier dysfunction.
Which HLA system genetic markers predispose to the development of gluten-induced enteropathy?
The development of gluten-induced enteropathy is predisposed by the presence of specific haplotypes (alleles) of the major histocompatibility complex. An obligatory genetic component of the disease is the presence of markers:
- HLA-DQ2
- HLA-DQ8
In pathogenesis, these molecules bind to gliadin peptides and present the antigen to gluten-specific CD4+ T lymphocytes. This triggers cytokine aggression and an immuno-inflammatory cascade, ultimately leading to damage to intestinal epithelial cells.
What specific autoantibodies are tested in the blood for the serological diagnosis of celiac disease?
For the serological diagnosis of celiac disease, specific autoantibodies, predominantly of the IgA class, against three targets are tested in the blood:
- tissue transglutaminase (antibodies to tTG / TG2);
- endomysium (antibodies to EMA);
- deamidated gliadin peptides (antibodies to DGP).
Antibodies to gliadin are also indicated in sources. A prerequisite is the preliminary assessment of the total IgA level in the blood. In selective IgA deficiency, IgG class antibodies to tissue transglutaminase and/or IgG class antibodies to endomysium are determined.
Celiac disease is a "whole" gliadin that the intestine cannot break down, so the immune system attacks its own villous structures.
Class and exam questions
Why does the $\alpha$-gliadin peptide trigger an immune response in celiac disease?
This peptide is resistant to hydrolysis by enzymes of the stomach, pancreas, and small intestine. As a result, it remains unchanged, penetrates tissues, and is recognized by the immune system as a foreign antigen.
What changes are found in feces in creatorrhea?
A large amount of unhydrolyzed nitrogen-containing substances, as well as altered and unaltered muscle and connective tissue fibers, are detected in the feces.
How does celiac disease manifest in adults?
In adults, the disease often has a covert or latent course. It can manifest as chronic diarrhea, flatulence, anemia, and chronic fatigue syndrome.
What else to study on this topic
- Functional gastric dyspepsia as a cause of maldigestion
- The role of enteropeptidase and trypsin in intestinal digestion
- Immunopathogenesis of epithelial damage in gluten-induced enteropathy
- Differential diagnosis of creatorrhea and steatorrhea
- Systemic manifestations of protein malabsorption syndrome
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