HC8 Clinical aspects of Celiac disease
Our body is designed to recognize foreign proteins. Food is also foreign, but food normally
doesn’t initiate an immune response.
- Digest
- Absorption
- Tolerate
Oral tolerance: Antigens (glycoproteins) that first come into contact with the immune
system through the mucous membranes are then tolerated.
Allergenic reaction: the tolerance is broken, and food will cause an immune reaction.
If the stomach be irretentive of the food and if it passes through undigested and crude, and
nothing ascends into the body, we call such persons coeliacs
- Ceoliac’s: Greek word for belly
1) Physiology of digestion: breakdown of food. Food consist of proteins, fats and
carbohydrates. These macromolecules cannot be taken up by the body and have to be
broken down.
- Digestive enzymes
o Amylase (digest starch in the mouth)
o Pepsin (breakdown proteins)
o Pancreas enzymes
- Gall: emulsifier for fat
Pancreatitis: inflamed pancreas → disruption of the secretion of the enzymes
- Chronic alcohol abuse
- Gall stones: the stones go through the pancreas to the stomach, the pancreas
enzymes get secreted within the pancreas instead of secreted to the intestine and
this causes a severe inflammation of the pancreas.
2) Absorption:
- Takes place in the small intestine
- Alcohol is absorbing in the stomach
- Majority of food is absorbed in the duodenum and jejunum (proximal part of
intestine)
o This part is damaged in celiac disease
- You can miss large intestine for absorption of food, because it mostly absorbing
water.
- Gut has folds and on top of that vilii that increases surface to absorb
3) Transport
→ disruption of digestion, absorption or transport can cause malabsorption
,Causes of malabsorption → via mucosal factors
- Loss of mucosal surface (short bowel)
o Absolute: Resections ischemia, inflammation (Crohn’s disease), cancer
o Mucosal diseases: Crohn’s disease, celiac disease
Crohns disease (left): no vilii, redness, swollen, ulcers Celiac disease (right): no vili
With celiac disease the villi disappear this will result in that the surface of the intestine
becomes smaller. This will make absorption of the food more difficult → malabsorption.
Clinical symptoms of malabsorption:
- Loss of calories → weight loss
- Diarrhea: the water and the food are not absorbing
- Flatulence (farts)
- Abdominal pain
- Deficiencies (electrolytes, Fe, vit B12, folic acid, Ca, Zn, vit KADE)
o Osteopenia = weak bones 🡪 by no calcium uptake
- Fatigue: no take up of nutrients and anemia (not enough blood, no iron is absorbing)
Malabsorption: stool analysis
Summary part 1:
- Proper digestive physiology requires:
o Breakdown of food (mechanical, chemical and enzymatic digestion)
o Absorption
o Transport
- Disturbance in any of these processes cause malabsorption syndrome
- Clinical signs include weight loss, diarrhea and deficiencies
, Part 2: Celiac disease
People with celiac disease cannot tolerate certain grains, proteins.
- Very prevalent, 1:200 people have celiac disease. But not all the people with celiac
disease are diagnosed (8%).
3 grains contain gluten: Wheat, rye (rogge), barley (gerst) → genetically the same
The seed has energy stored to come above the ground to reach for the sunlight. Also,
proteins are stored, the majority of the proteins are gluten.
- Grain contains a lot of carbohydrates and 10% of proteins → major protein is gluten
- Celiac has features of both a food intolerance and an autoimmune disease
(autoantibodies)
Why are gluten proteins harmful for celiac patients?
1. Gluten has a high content of glutamine and proline → resistance to enzymatic
digestion in the stomach → large PQ peptides in the duodenum → immune
activation
2. Patients with Celiac almost always have HLA-DQ2/8
Gluten peptides are not fully degraded, they enter the small intestine → they are
absorb by the small intestine → cells of the immune system picks up the gluten
(APC’s) → when you are HLA-DQ2/8 positive, the gluten binds to it and the APC
present it to T-cells → the T-cells are activated and start to secrete cytokines → this
cause a little damage to the mucosa.
We don’t know why a small part of people with the HLA-DQ2/8 have an inflammatory
reaction → difference between normal and celiac people = tolerance is broken
When the mucosa gets inflamed transglutaminase (tTG) is released from the cells, this
enzyme is very important for the regeneration of the mucosa → tTG will bind to the gluten
peptide → tTG enzymatically changes the conformation of the gluten peptide = deamidated
gluten → the deamidated gluten have an even higher affinity for HLA-DQ2/8 → the T-cells
gets now fully activated, start to secrete cytokines and the villi gets destructed (flat mucosa).
BUT then: autoantibodies will be formed against the complex with transglutaminase bind to
gluten (transglutaminase antibodies) → transglutaminase antibodies can eb measured in the
blood, more inflammation = higher amount of the antibodies.
Our body is designed to recognize foreign proteins. Food is also foreign, but food normally
doesn’t initiate an immune response.
- Digest
- Absorption
- Tolerate
Oral tolerance: Antigens (glycoproteins) that first come into contact with the immune
system through the mucous membranes are then tolerated.
Allergenic reaction: the tolerance is broken, and food will cause an immune reaction.
If the stomach be irretentive of the food and if it passes through undigested and crude, and
nothing ascends into the body, we call such persons coeliacs
- Ceoliac’s: Greek word for belly
1) Physiology of digestion: breakdown of food. Food consist of proteins, fats and
carbohydrates. These macromolecules cannot be taken up by the body and have to be
broken down.
- Digestive enzymes
o Amylase (digest starch in the mouth)
o Pepsin (breakdown proteins)
o Pancreas enzymes
- Gall: emulsifier for fat
Pancreatitis: inflamed pancreas → disruption of the secretion of the enzymes
- Chronic alcohol abuse
- Gall stones: the stones go through the pancreas to the stomach, the pancreas
enzymes get secreted within the pancreas instead of secreted to the intestine and
this causes a severe inflammation of the pancreas.
2) Absorption:
- Takes place in the small intestine
- Alcohol is absorbing in the stomach
- Majority of food is absorbed in the duodenum and jejunum (proximal part of
intestine)
o This part is damaged in celiac disease
- You can miss large intestine for absorption of food, because it mostly absorbing
water.
- Gut has folds and on top of that vilii that increases surface to absorb
3) Transport
→ disruption of digestion, absorption or transport can cause malabsorption
,Causes of malabsorption → via mucosal factors
- Loss of mucosal surface (short bowel)
o Absolute: Resections ischemia, inflammation (Crohn’s disease), cancer
o Mucosal diseases: Crohn’s disease, celiac disease
Crohns disease (left): no vilii, redness, swollen, ulcers Celiac disease (right): no vili
With celiac disease the villi disappear this will result in that the surface of the intestine
becomes smaller. This will make absorption of the food more difficult → malabsorption.
Clinical symptoms of malabsorption:
- Loss of calories → weight loss
- Diarrhea: the water and the food are not absorbing
- Flatulence (farts)
- Abdominal pain
- Deficiencies (electrolytes, Fe, vit B12, folic acid, Ca, Zn, vit KADE)
o Osteopenia = weak bones 🡪 by no calcium uptake
- Fatigue: no take up of nutrients and anemia (not enough blood, no iron is absorbing)
Malabsorption: stool analysis
Summary part 1:
- Proper digestive physiology requires:
o Breakdown of food (mechanical, chemical and enzymatic digestion)
o Absorption
o Transport
- Disturbance in any of these processes cause malabsorption syndrome
- Clinical signs include weight loss, diarrhea and deficiencies
, Part 2: Celiac disease
People with celiac disease cannot tolerate certain grains, proteins.
- Very prevalent, 1:200 people have celiac disease. But not all the people with celiac
disease are diagnosed (8%).
3 grains contain gluten: Wheat, rye (rogge), barley (gerst) → genetically the same
The seed has energy stored to come above the ground to reach for the sunlight. Also,
proteins are stored, the majority of the proteins are gluten.
- Grain contains a lot of carbohydrates and 10% of proteins → major protein is gluten
- Celiac has features of both a food intolerance and an autoimmune disease
(autoantibodies)
Why are gluten proteins harmful for celiac patients?
1. Gluten has a high content of glutamine and proline → resistance to enzymatic
digestion in the stomach → large PQ peptides in the duodenum → immune
activation
2. Patients with Celiac almost always have HLA-DQ2/8
Gluten peptides are not fully degraded, they enter the small intestine → they are
absorb by the small intestine → cells of the immune system picks up the gluten
(APC’s) → when you are HLA-DQ2/8 positive, the gluten binds to it and the APC
present it to T-cells → the T-cells are activated and start to secrete cytokines → this
cause a little damage to the mucosa.
We don’t know why a small part of people with the HLA-DQ2/8 have an inflammatory
reaction → difference between normal and celiac people = tolerance is broken
When the mucosa gets inflamed transglutaminase (tTG) is released from the cells, this
enzyme is very important for the regeneration of the mucosa → tTG will bind to the gluten
peptide → tTG enzymatically changes the conformation of the gluten peptide = deamidated
gluten → the deamidated gluten have an even higher affinity for HLA-DQ2/8 → the T-cells
gets now fully activated, start to secrete cytokines and the villi gets destructed (flat mucosa).
BUT then: autoantibodies will be formed against the complex with transglutaminase bind to
gluten (transglutaminase antibodies) → transglutaminase antibodies can eb measured in the
blood, more inflammation = higher amount of the antibodies.
