Malabsorption syndrome.pptx

1. Malabsorption syndrome
Semey 2021
NJSC "Semey Medical University"

2. Malabsorption syndrome
Malabsorption syndrome ("malabsorption" - "poor absorption") is a
complex of disorders resulting from malabsorption and impaired
breakdown of nutrients, vitamins and microelements in the small intestine.
Currently, in a broad sense, this term also includes the syndrome of
impaired digestion, since various disorders of the processes of digestion of
food lead, for the second time, to impairment of the processes of
absorption.
The term "malabsorption syndrome" does not fully reflect the essence
of the entire set of complex physiological and pathological processes in the
child's body in this condition. In a broad sense, the term also includes
maldigestion syndrome. Malabsorption + maldigestion = malassimilation or
malnutrition syndrome.

3. • Maldigestion - a violation of the digestion of nutrients in the
gastrointestinal tract - may be associated with a violation of digestion in the
intestinal lumen (abdominal maldigestion) or with a violation of membrane
digestion in the brush border of the mucous membrane of the small
intestine (membrane maldigestion).
• Malassimilation - in fact, is a term that unites a complex of changes in
digestion and absorption, which determines its use in international
terminology to characterize both violations of the processes of breakdown
of the main components of food, and absorption of the final products of
their hydrolysis.

4. Classification
Malabsorption syndrome can be genetically determined (primary
forms) or caused by other diseases of the gastrointestinal tract (secondary
forms). The term "malabsorption syndrome" still includes more than 70
diseases and syndromes. The most widespread classification of enteric
insufficiency was A.V. Frolkis:
By the etiology and nature of functional disorders:1. Congenital and
hereditary acquired. Primary - associated with hereditary and congenital
disorders of the structure of the small intestine and fermentopathies:
Primary digestive failure of the small intestine (maldigestion syndrome)
Primary insufficiency of the absorption function of the small intestine
(malabsorption syndrome)

5. 2. Acquired (secondary, mainly generalized);
• Enterogenic: enteritis, Crohn's disease, infectious, parasitic, vascular and
other intestinal diseases.
• Gastrogenic: peptic ulcer, gastritis, stomach cancer, etc.
• Pancreatogenic: pancreatitis, cystic fibrosis, cancer, islet tumors, etc.
• Hepathogenic: acute and chronic liver diseases, intrahepatic and
extrahepatic cholestasis.
• Post-resection (due to operations on the gastrointestinal tract).
• Endocrine: diabetes mellitus, hyper- and hypothyroidism,
hypoparathyroidism, etc.
• Medication (neomycin, cholestyramine, colchicia, PASK, methyldopa,
methotrexate, antacids, ethyl alcohol, phenindione, metformin, etc.)

6. According to the clinical course:
A. Latent (detected only by functional tests).
B. Explicit:
With initial clinical manifestations.
With severe clinical manifestations.
Terminal stage.
Among the diseases occurring with malabsorption syndrome, the three most
common are of interest:
• disaccharidase deficiency;
• celiac disease (celiac disease);
• cystic fibrosis (cystic fibrosis of the pancreas)

7. Lactase deficiency
Lactase deficiency (LN) is a congenital or acquired condition
characterized by a decrease in the activity of the lactase enzyme that breaks
down milk sugar lactose in the small intestine and is latent or manifest.
Congenital insufficiency is explained by a mutation of the structural gene
responsible for the synthesis of lactase, as a result of which this enzyme is
not synthesized (alactasia), or its inactive or inactive form is formed
(hypolactasia).

8. The role of lactose in child development
Lactose-disaccharide, which is an essential nutrient
at an early age, as it serves as the main source of energy
for babies in the first months of life. Lactose is the main
carbohydrate in human milk, although galactose,
fructose and other oligosaccharides are also present in
small amounts. Lactose value: - when lactose is broken
down by the microflora of the large intestine, lactic acid
is formed, which suppresses the growth of pathogenic
bacteria, putrefactive and gas-forming flora; - it
stimulates the growth of normal intestinal microflora
and acts as a prebiotic; - lowers the pH of intestinal
contents; - participates in the synthesis of galactose,
which is necessary in the first months of life for the
synthesis of galactocerebrosides in the brain: -
participates in the synthesis of B vitamins; - affects the
absorption of Mg, Mn, Ca; - stimulates its own
enzymatic activity.

9. The decrease in lactase activity can be complete (alactasia) or
partial (hypolactasia).
By origin, primary (decrease in enzyme activity with
morphologically unchanged enterocyte) and secondary (decrease in
enzyme activity, directly related to damage to the enterocyte) are
isolated.
Variants of primary FN are: genetically determined congenital FN,
transient FN of premature or immature children at the time of birth,
as well as constitutional FN, or adult type.
Secondary FN is observed in a number of lesions of the small
intestine, both infectious and non-infectious. These include: celiac
disease in the active stage of the disease, immune and non-immune
forms of intolerance to cow's milk proteins, food allergies, post-
infectious enterocolitis, giardiasis, intestinal infections, HIV,
primary immunodeficiencies, Crohn's disease, post-radiation
enterocolitis, short bowel syndrome and others.
Classification

10. Etiopathogenesis.
The activity of lactase in the intestine of the fetus is low
until the 12-13th week of gestation, then it increases, especially
in the third trimester of pregnancy, and reaches its maximum
values ​​by the 39-40th week. Therefore, in premature newborns,
this indicator can be up to 50% of the value of the lactase
activity of children born after the 36th week, in contrast to
other disaccharidases. In the postnatal period, the maximum
activity is observed at 2–4 months of life, when the child
receives the main amount of carbohydrates in the form of
lactose. Then, after 6 months of life, carriers of the recessive
genotype show a gradual decrease in the enzyme activity with
a significant drop by 1.5–5 years. The gene encoding the
synthesis of lactase in the body, the LCT gene, is located on
chromosome 2q21.

11. Congenital FN is a rare disease with an incidence of 1: 60,000 and is
inherited in an autosomal recessive manner. It is especially common in the
Finnish population. With it, of the four described mutations, the nonsense
mutation Y1390X is more common.
Thus, the normal gastrointestinal tract of most newborns and infants is able
to utilize lactose. However, with age, some of this ability is lost, which is
considered as a genetically programmed inherited autosomal recessive
process. It begins to form after the end of breastfeeding, while the symptoms
increase as the enzyme activity decreases, so it can clinically manifest itself
at any age.

12. With insufficient enzyme activity, hydrolysis of lactose in the parietal
layer of the small intestine to glucose and galactose does not occur, and
undigested lactose enters the large intestine. Its utilization by anaerobic
flora to lactic acid, carbon dioxide, water, short-chain fatty acids, methane,
hydrogen will be manifested by increased gas production and flatulence.
The high osmotic potential of lactose and fatty acids will cause osmotic
diarrhea with acidic stool pH. It should be noted that for children, a certain
amount of lactose in the large intestine is necessary, since its residual
fermentation by the microflora is important for the formation and
maintenance of the intestinal biocenosis.

14. Clinical picture
The clinical picture of various types of lactase deficiency is characterized
by attacks of intestinal colic, diarrhea, regurgitation, vomiting, bloating,
loss of appetite, anxiety, insufficient weight gain and, as a result,
hypotrophy. Stools are frequent, watery, frothy, with a lot of flatulence,
sometimes green, with a sour odor. Characterized by persistence of
symptoms, no significant effect in the treatment of probiotics, enzymes.

15. Congenital lactase deficiency is characterized by a
severe course due to severe diarrhea with the
development of dehydration, electrolyte disturbances. It
manifests itself from the first days of life when feeding
both with breast milk and with any mixtures based on
cow's and goat's milk, the symptoms increase as the
amount of food increases. The frequent detection of
opportunistic microflora in the feces of patients
sometimes leads to an erroneous diagnosis of acute
gastroenteritis and unjustified prescription of antibiotics.
Cancellation of milk leads to an improvement in the
condition, an increase in body weight. The resumption of
milk feeding is accompanied by a relapse of symptoms.

16. Transient lactase deficiency is usually manifested by intestinal colic,
combined with watery stools. At the same time, the child has no signs of an
infectious process, the stool remains yellow, without inflammatory changes, the
child gains weight. This corresponds to the symptomatology of functional
disorders of the gastrointestinal tract, about a third of children suffering from
infantile colic are based on FN. The appointment of an enzyme or low-lactose
mixture improves the condition of the child.
Primary lactase deficiency that develops at a later age (after 5 years)
usually does not have such vivid symptoms, since milk ceases to be a staple
food, and the load of lactose is not as great as in infants. At the same time, the
colon microbiota can adapt to the intake of a small amount of lactose and the
saccharolytic bacteria of the colon, actively multiplying, can level the clinical
symptoms of the disease. Fermented milk products containing a low percentage
of lactose and promoting the growth of the saccharolytic flora are generally
better tolerated than milk. Vivid symptoms of intestinal disorders usually
appear only after taking a large amount of milk. The degree of clinical
manifestations at an older age does not always correspond to the true degree of
enzymatic insufficiency, and the final judgment about it is possible only after
an appropriate examination of the child.

17. Secondary lactase deficiency develops at any age on the background
of prolonged intestinal infections, especially rotavirus, food allergy, celiac
disease, etc. Clinical manifestations of fermentopathy may be indistinct due
to the symptoms of the underlying disease, therefore, anamnestic data on
good or poor milk tolerance is crucial for diagnosis do not play, however, the
abolition of milk, as in congenital forms, leads to an improvement in the
condition

18. The diagnosis is made based on the following criteria:-
genealogical data, genetic research. Primary lactase deficiency of the
adult type is characterized by the presence of genes C / T-13910 and C /
T-22018) located on chromosome 221;-diet diagnostics: reduction of
dyspeptic symptoms when switching to a lactose-free diet; - a flat
glycemic curve (that is, with an increase in glycemia less than 1.1 mmol
/ l) after loading with lactose at a dose of 2 g / kg of body weight:-
scatological data (an increase in starch, fiber, a decrease in fecal pH less
than 5.5):- determination of carbohydrates in feces using strips
"Testape", Benedict's test (normally the indicator should not exceed
0.25% in children under 12 months and be negative after 1 year).-
determination of lactase activity in biopsies of the mucous membrane of
the small intestine. This method is the gold standard for the diagnosis of
lactase deficiency, however, the invasiveness, complexity and high cost
of the method limits its use in everyday practice:- determination of the
content of hydrogen, methane or 14C-labeled CO in the exhaled air. The
methods reflect the activity of microflora in lactose fermentation.
Method limitation: high cost.
Diagnostics

19. Celiac disease (ICD code 10 k90) is a systemic
immunopathological disease caused by gluten and
developing against the background of a genetic
predisposition. This definition is given in the latest
2012 international guidelines for the diagnosis of
celiac disease of the European Society of Pediatric
Gastroenterologists, Hepatologists and Nutritionists
ESPGHAN. For all its brevity and simplicity, this
definition is very capacious, since it reflects the
essence of the disease, emphasizing that 3
components are necessary for its
development:cereal protein gluten;genetic
predisposition;pathological response of the local
intestinal immune system to gluten.
ЦЕЛИАКИЯ

20. Risk groups for celiac disease: • Persons
with chronic diarrhea and IBS; • Lagging
physical and / or sexual development,
miscarriage; • With osteoporosis; • IDA or
megaloblastic anemia; • Close relatives
(parents and siblings) of celiac patients; •
Patients with "associated" autoimmune
diseases; • Children with Down syndrome,
Williams and Shereshevsky. Turner A
screening is recommended for them to rule
out celiac disease.

21. Celiac disease is a genetically determined disease associated with the
antigens of the main human histiocompatibility complex (MCH II) HLA-DQ
2 and HLA-DQ 8. The type of inheritance is autosomal dominant. The
prevalence of the disease in certain regions and countries of the world ranges
from 12 to 203 cases per 100,000 people (average 90: 100,000). It is much
more common in regions where foods from wheat, rye, and oats prevail in
the diet, much less often in China and Africa, which is apparently associated
with the consumption of rice and corn by the population of these regions. In
recent years, this diagnosis has been made more and more often, because
subclinical forms are better recognized. Probably, the real prevalence of
pathology is much higher than the available data; manifestations of the
disease mainly occur in childhood, although they are also possible in adults.

22. In healthy individuals, gluten does not damage the mucous membrane
of the small intestine, since specific enzymes break down (hydrolyze) it to
non-toxic substances. With celiac disease, there is a hereditary deficiency of
these enzymes. In this regard, gliadin accumulates, which has a toxic effect
on enterocytes, which leads to dysfunction of the small intestine. The total
absorption surface of the intestinal mucosa decreases as a result of
compensatory lymphoplasmacytic infiltration of its own plate, followed by
atrophy of the villi and proliferation of crypt cells.

23. Pathogenesis
The leading role is played by gluten (protein of wheat, rye,
barley, oats) in genetically predisposed individuals after eating these
products. In 2002, a 33-dimensional peptide initiating an immune-
inflammatory response was isolated from recombinant a 2 -gliadin.
Gliadin peptides bind to HLADQ 2 / DQ 8 molecules with their
subsequent presentation to gluten-specific CD 4+ T-lymphocytes
and an immune-inflammatory process occurs in the mucous
membrane of the small intestine.
Multifactorial disease is a combination of genetic and external
factors, as well as trigger (intrauterine malnutrition, mother's
smoking during pregnancy).
Binding of HLA DQ 2 and DQ 8 gliadin to a molecule for
antigen presentation to T cells (CD 4) of the lamina propria.The
enzyme tissue transglutaminase (TSH) selectively deamidates the
glutamine residues of gliadin.Antibodies to TSH inhibit
transforming growth factor-β, as a result of which the differentiation
of epithelial cells is suppressed.

24. A sharp decrease in the digestive function of the intestine
(atrophy of intestinal villi + ↓ activity of intestinal and pancreatic
enzymes + violation of hormonal regulation of digestion) →
malabsorption syndrome.
Damage to the glycocalyx, the brush border of enterocytes with
membrane enzymes (lactase, sucrase, maltase, isomaltase,
dipeptidase) → intolerance to the corresponding nutrients.Violation
барьерной функции тонкой кишки → попадание во внутреннюю
среду большого количества нерасщепленных белков с
антигенными свойствами.
Changes in the composition of the intestinal microflora →
allergic reactions;
"Deficiency" syndromes: osteopenia, osteoporosis, anemia,
hemorrhagic syndrome, violation of skin and hair trophism, etc.;
Violation of the trophism of the central nervous system,
autoimmune mechanisms with damage to the pituitary gland → a
decrease in the level of growth hormone and persistent growth
retardation in children

25. Celiac disease classification
Periods:
1 – latent
2 -clinical manifestation (active)
3 -remission (initial remission-3-6 months. GFD; - incomplete
remission, clinical and serological, after 3-6 months. strict
BGD; - complete remission (clinicoserological,
morphological remission) not earlier than 1-1.5 years of strict
GFD)
4 -decompensation.

26. Clinical course options
The disease can be typical, atypical and latent
(subclinical). Depending on the prevailing syndromes,
several clinical forms of typical celiac disease are
distinguished: hemorrhagic, with bone disorders,
edematous (protein deficient), anemic and septic. In
older children, an atypical course is more often
observed with vague complaints and an almost
complete absence of characteristic symptoms, despite
the presence of specific changes in the mucous
membrane of the small intestine. Diagnosis of this
variant of the disease is difficult, and sometimes
impossible. The subclinical form, obviously, occurs
much more often than is diagnosed, and it is also very
difficult to establish it.

27. The most significant clinical symptoms are dystrophy (weight loss and
stunting), diarrhea, steatorrhea, and central nervous system damage. The
clinical picture develops gradually - the child loses appetite, lethargy,
weakness, regurgitation, vomiting, diarrhea appear. The weight curve at first
becomes flat, and then the body weight decreases steadily. Children are
significantly behind in growth, especially if the disease debuted in the first
year of life. The patient's appearance is typical: a sad facial expression, poor
facial expressions ("unhappy look"), a large belly and thin limbs ("a
backpack on legs").

28. In every fourth child, the disease does not begin with
diarrhea, but on the contrary, the main clinic is preceded by
constipation, in some cases only polyfecal matter is detected
without disturbing the nature of the stool. Stool changes are of
the utmost importance: feces are sharply fetid, abundant (up to
700-1500 g / day at a rate of 100-200 g / day), increased up to
3-5 times, frothy, acholic (with a grayish tint), shiny (due to
significant content of fat and fatty acids).
Over time, additional symptoms inevitably arise,
associated with damage to other digestive organs (liver,
pancreas, duodenum, etc.). The hepatobiliary system is
involved in the process. Cases of a combination of celiac
disease and biliary cirrhosis of the liver have been described.
Patients have moderately expressed hepatomegaly, symptoms
of cholestasis, disorders of the biochemistry of bile (a decrease
in the concentration of cholic acid, cholesterol).

29. The exocrine and endocrine functions of the pancreas are
impaired. The concentration of bicarbonates in the pancreatic juice
decreases, the activity of pancreatic enzymes is significantly
reduced. A number of researchers point to secondary insular
insufficiency, manifested by symptoms of polydipsia and polyuria
during an exacerbation of the disease; some children are obese
during the period of remission. All types of metabolism change
profoundly, especially protein and amino acid, due to the
predominance of anabolic processes in the growing body and an
increased need for plastic material. A pronounced deficiency of
both essential amino acids (alanine, threonine, phenylalanine,
leucine, isoleucine, glycine, etc.) and nonessential ones has been
established. Amino acid deficiency is combined with significant
losses of free amino acids from urine and feces. Dystrophy, which
develops in celiac disease, is caused by impaired digestion of
proteins and absorption of amino acids due to a defect in the
transport mechanisms of the intestinal mucosa and kidneys.

30. Changes in lipid metabolism are manifested by a
decrease in the concentration of total lipids, cholesterol,
phospholipids and an increase in the content of non-
esterified fatty acids, ketone bodies in the blood serum.
Persistent steatorrhea is characteristic. No less pronounced
disorders are found on the part of carbohydrate
(hypoglycemia, decreased glucose tolerance), electrolyte
and microelement metabolism (a decrease in the
concentration of calcium, phosphorus, potassium, sodium,
zinc, selenium, magnesium, iron, etc.) in the blood. All
children have disorders of the central nervous system -
metabolic-toxic encephalopathy. Patients become irritable,
capricious, negative, lose previously acquired skills and
abilities, lag behind in the development of speech.

31. Clinically, metabolic disorders in celiac disease are manifested
by rickets, polyhypovitaminosis (atrophic glossitis, severe dry skin
with pityriasis peeling, follicular hyperkeratosis, hypo- and
hyperpigmentation of the skin), anemia, alopecia, degeneration of
the nail plates, fractures of the tubular bone types. Due to secondary
immunodeficiency (cellular and humoral) and profound metabolic
disorders, sick children are prone to frequent colds, which are
difficult and long-lasting. The most formidable complication of
celiac disease is sepsis.

33. Diagnostic criteria for celiac disease are 3 signs: 1) characteristic
morphological changes in biopsies of the mucous membrane of the
duodenum or jejunum: subtotal or total atrophy of the mucous membrane;
2) improvement of clinical and laboratory data against the background of a
gluten-free diet (regression of signs of the disease); 3) the appearance of
symptoms of the disease after a provocative test with gluten or a violation
of the gluten-free diet.
Diagnostics in groups of genetic risk (relatives of the 1st degree of
relationship):
Stage 1. Genetic
Stage 2. Clinical and anamnestic
Stage 3. Serological
Stage 4. Histological
Diagnostics.

34. Serological examination:
• Antibodies to tissue transglutaminase (anti-TSH) and endomysium (anti-EMA) Ig A / G class
• Antigliadin antibodies (AGA) - considered nonspecific
• Antibodies to deamidated gliadin peptides (a. DPG).
Genetic research:
• Determination of HLA alleles - DQ 2 / DQ 8. A negative result can rule out celiac disease in
most patients, but in 30% of the healthy population it can be positive.
Provocative test (gluten load) indications:
1. The survey was carried out with a delay (more than 2 -3 months after the beginning of the
strict GDD);
2. 2. In children with a history of short duration of gluten load;
3. 3. In children with a history of low gluten load
4. 4. Sprinkle gluten powder into food.
Biopsy after 6 months, 2 years, follow-upEGD and biopsy of CO from the bulb and the
descending section 12 sc - 4 biopsies. Flattening or absence of folds (intestine in the form of a
"pipe"), transverse striation or cellular pattern ("honeycomb") and micronodular structure of
the mucosa

35. Additional research for celiac disease:
• General blood analysis
• General urine analysis
• Biochemical blood test: total protein, protein fractions, total lipids,
cholesterol, glucose, alt and ast, alkaline phosphatase, bilirubin and
fractions, calcium, phosphorus, sodium, potassium, serum iron;•
blood lipidogram;
• Coprogram, fecal lipidogram;
• D-xylose test;
• Research of thyroid hormones, STH
Densitometry of the lumbar spine;
• ultrasound of the liver, gallbladder, pancreas, kidneys, thyroid gland,
pelvic organs in girls, testicles in pubertal boys;

36. In the study of peripheral blood in children, various degrees of
hypochromic anemia with poikilocytosis, anisocytosis, a decrease in
the level of reticulocytes are revealed, which indicates a deficient
nature of anemia. A biochemical blood test indicates a deficiency of
protein (hypoproteinemia, dysproteinemia), iron, calcium,
phosphorus, zinc, selenium, magnesium and other minerals,
hypocholesterolemia is also found сoprogram changes are of great
diagnostic value.
Characterized by the detection in feces of a large amount of
neutral fats (steatorrhea), starch and undigested fiber; decrease in
fecal pH. Almost always, intestinal dysbiocenosis is detected with a
predominance of the growth of conditionally pathogenic flora, a
significant deficiency of lacto- and bifidumbacteria. To assess the
degree of intestinal absorption disorders in pediatric practice, a test
with D-xylose is used, the excretion of which in the urine of patients
with celiac disease is significantly reduced (less than 15% of the
administered drug within 9 hours). When loaded with disaccharides,
flat sugar curves are found. It is important to clarify the daily fat loss
using the Van de Kamera method.

37. Differential diagnosis.
1. Malabsorption syndrome: cystic fibrosis, Schwachman-
Diamond syndrome, pancreatic lipase deficiency, autoimmune
enteropathy, congenital intestinal lymphangiectasia
(Waldmann's syndrome), alpha-beta lipoproteinemia, trypsin
enterokinase deficiency.
2. Delayed growth and development of the child: pituitary
dwarfism, syndromic forms of short stature
3. Gastrointestinal form of food allergy to wheat