malabsorptive disorders of the intestine are categorized within this lecture into three categories: disorders related to insufficient digestive elements (such as lactase insufficiency), tropical sprue, celiac sprue. tropical sprue afflicts those who visit certain tropical countries and is thought to be related to infection by an unknown organism perhaps associated with an underlying nutritional deficiency. tropical sprue begins as foul, bulky stools characteristic of fat malabsorption, then progresses to systemic manifestations of malabsorption: weight loss, weakness, glossitis, stomatitis, cheilosis, hyperpigmentation, dry skin. a CBC might show megaloblastic anemia and a chem screen might show decreased levels of serum protein, calcium, phosphorous, cholesterol, prothrombin, HCl, but normal pancreatic function. decreased urine and serum levels in the D-xylose test is also used to diagnose tropical sprue.
gluten enteropathy is a general condition that involves a reactivity to gluten that afflicts up to 1/3 of the US population. of this subset, 5% have a more serious condition called celiacs which results in inflammation of the intestinal lining that leads to villous atrophy and malabsorption. traditionally a disease that afflicted young children, celiacs is now more commonly diagnosed in mid age adults- in particular those from western european, indian, south american, north african countries. there have been some hereditary factors identified such as certain allelles that are present in celiacs patients in the HLA-DQ2 and DQ1 genes, but for the most part the etiological mechanisms are unclear. celiacs patients might present with diarrhea / constipation, abdominal distention (in infants and children due to oncotic pressure changes resulting from low albumin levels), anemia / fatigue, hair loss, aphthous ulcers, dermatitis herpetiformis. lab tests of celiacs patients might show anemia of various types with an increased RDW, AST alkaline phosphatase with low albumin / plasma protein levels. other tests that can be performed are biopsy after gluten ingestion, and testing for IgA to gliadin, endomysial, tissue transglutaminase. two severe complications of celiacs that might arise are malignancy and osteoporosis.
the third major malabsorptive disorder that we learned about is lactase deficiency, the enzyme that digests lactose into glucose and galactose. this disorder is widespread and affects about 3/4 of the world's population, with a higher prevalence in native american, asian, and african american races. lactase deficiency can be congenital (very rare), primary (due to an inherent lack of production), or secondary (due to an acute illness or injury such as gastroenteritis or chemotherapy). it might result in a range of symptoms, from mild abdominal discomfort to severe diarrhea upon lactose ingestion. lactase deficiency is best diagnosed with the hydrogen breath test, which would measure abnormally high levels of hydrogen in the breath after ingestion of lactose. another method is simply to eliminate lactose from the diet and observe for change of symptoms.
questions
tropical sprue...
1. what is the etiology of tropical sprue?
2. what is the first stage of symptoms for tropical sprue?
3. what is the second stage of symptoms for tropical sprue?
4. what does a PE for tropical sprue patients reveal?
5. a CBC for tropical sprue patients might show...
6. what would stool analysis for a tropical sprue patient show?
7. what would a chem screen for a tropical sprue patient show?
8. what is the D-xylose absorption test?
gluten enteropathy and celiacs disease...
9. what is celiacs disease?
10. what is the difference between gluten enteropathy and celiacs?
11. why do babies with celiacs have big bellies?
12. what are the factors that increase susceptibility to a negative reaction with gliadin?
13. what are regions of the world associated with celiacs?
14. what percentage of americans have gluten enteropathy?
15. what percentage of americans have celiacs?
16. what are the symptoms of celiacs for infants?
17. what are the symptoms of celiacs for children?
18. what are the symptoms of celiacs for adults?
19. what percentage of patients with dermatitis herpetiformis has celiacs?
20. what will lab tests show for a celiacs patient?
21. what are the histological findings for a celiacs patient?
22. what is the definitive diagnosis for celiacs disease?
23. what are the IgA tests used to diagnose celiacs?
24. how specific is the diagnostic finding of tissue transglutaminase IgG?
25. what are some diseases associated with celiacs?
26. what are two important complications associated with celiacs?
lactase deficiency...
27. what is lactose intolerance?
28. how much of the world's population has lactase deficiency?
29. what are the different types of lactose intolerance?
30. what are two factors that can cause secondary lactose intolerance?
31. what are the signs and symptoms of lactase deficiency?
32. what is the lab test that can diagnose lactase deficiency?
33. what is another method for diagnosing lactase deficiency?
answers
1. idiopathic, or nutritional deficiency, infection.
2. bulky, pale, foul stools from fat malabsorption.
3. weight loss, flatulence, cramps, pallor, weakness, irritability.
4. signs of vitamin deficiency:
glossitis, stomatitis, cheilosis, hyperpigmentation, dry skin, abdominal distention, tenderness, edema, weight loss.
5. megaloblastic anemia.
6. fat malabsorption.
7. decreased:
serum protein
calcium
phosphorous
cholesterol
prothrombin
HCl
...and normal pancreatic function
[pcpcphp]
8. a test in which 25mg D-xylose is ingested orally, followed by 5 hour urine level measurement and 1 hour serum level measurement.
9. an immune related inflammation of the intestines related to gliadin which leads to loss of vili and malabsorption.
10. gluten enteropathy is a broader term than celiacs, referring to any condition that reacts to gliadin.
11. low albumin levels lead to changes in oncotic pressure which causes fluid to leak out into tissues.
12. some hereditary factors have been identified such as HLA-DQ2 and DQ1 genes, but precise mechanism is basically unknown.
13. western europe, india, south america, north africa,
14. 30%.
15. about 1/133.
16. diarrhea
abdominal distention
failure to thrive
anorexia, vomiting
psychomotor impairment
[diarrhea, distention, thrive, anorexia, impairement] [the infant's diarrhea impaired his intended to thrive on anorexia]
17. diarrhea / constipation
anemia
loss of appetite
secondary dentition
may have abdominal distention
[basically same as infants + secondary dentition?]
18. diarrhea / constipation
anemia / fatigue
dyspepsia / abdominal pain / weight loss
hair loss
aphthous ulcers
dermatitis herpetiformis
angular chelitis
cardiomyopathy
osteoporosis
weakness
[dad had a cow]
19. 75-90%.
20. anemia / increased RDW
increased AST, alkaline phosphatase
low albumin / plasma protein, cholesterol
21. villous atrophy is the characteristic finding.
22. ingest gluten and do a biospy.
23. anti gliadin IgA, anti endomysial IgA, anti tissue transglutaminase IgA
24. 100% specific.
25. type 1 diabetes, autoimmune thyroid disease
26. osteoporosis and malignancy (enteropathy associated t cell lymphoma)
27. a deficiency in lactase in the brush border resulting in an inability to digest lactose.
28. approximately 75%.
29. congenital (very rare), primary (due to inherent lactase production deficit), secondary (acute illness or injury)
30. acute gastroenteritis and chemotherapy.
31. ranges from minor abdominal discomfort to severe diarrhea in response to lactose, nausea
32. hydrogen breath test: measuring hydrogen breath levels after lactose ingestion.
33. eliminating lactose containing foods from the diet and observing change in symptoms.
Showing posts with label celiac disease. Show all posts
Showing posts with label celiac disease. Show all posts
Sunday, February 14, 2010
Tuesday, February 10, 2009
immunology: hypersensitivity
hypersensitivity is the phenomenon where the immune system's cells overreact against non-pathogenic antigen. there are four classifications based on the mechanism of the immune response. type I hypersensitivity is the allergic response; involves a class switch from IgM to IgE and a Th2 based response. an example is an allergy to corn: corn particles are ingested by dendritic cells and macrophages in the intestinal lymph tissue and presented to a CD4 cell. if co-stimulatory molecules are expressed, and the cytokines IL-10 and IL-15 are secreted, the CD4 cell differentiates into a Th2 cell, secreting IL-4,5,13. IL-4 causes a class switch from IgM to IgE, which causes binds to mast cells and causes degranulation and also secretion of TNF-alpha (TNF-alpha damages intestinal epithelium, contributing to leaky gut, potentially worsening the allergic response).
type II hypersensitivity is characterized by release of antibodies specific for molecules on cell surface. an example is the hypersensitivity to penicillin, which can occur when penicillin binds to a glycosylated protein on red blood cells. antibodies specific for the penicillin then bind to the redbloodcell/penicillin and are subsequently attacked by macrophages, resulting in hemolytic anemia (note that this is not an autoimmune response because the macrophages are targeting the penicillin primarily).
type III hypersensitivity is characterized by antibodies that are specific for soluble proteins- generally only occurs with high levels of soluble proteins. this often results in the formation of large antibody-soluble antigen complexes which can grow to block vessels or tubules. when this occurs macrophages and neutrophils are recruit to phagocytose the complexes and often damage the peripheral tissue by way of ROS production.
type IV hypersensitivity is a t-cell mediated response against antigen. the example given to us is celiac disease, which is a hypersensitivity to a peptide in wheat, gliadin. wheat is transported in from the lumen of the gut into the peyer's patches by microfold cells, where it can be ingested by macrophages and dendritic cell. these cells present the wheat peptide in an MHC to a CD4 t cell; if there is no co-stimulatory molecule expressed as well, this leads to a state of anergy and peripheral tolerance in the t cell. if there is co-stimulatory molecule expression (note that the increased microflora that enters the intestinal layers due to leaky gut can increase the likelihood of expression of co-stimulatory molecules) the CD4 t cell will be differentiated into a Th3 cell, which will proliferate and secrete TGF beta, resulting in a state of tolerance.
questions
different hypersensitivity mechanisms...
1. what is type I hypersensitivity characterized by?
2. what is type II hypersensitivity characterized by?
3. what is type III hypersensitivity characterized by?
4. what is type IV hypersensitivity characterized by?
5. what does an immune response dominated by Th2 result in? Th1?
6. what type of hypersensitivity is a penicillin hypersensitivity? describe the immune response.
7. why is a penicillin hypersensitivity not considered an autoimmune disease considering that red blood cells die in the process?
8. describe a typical type III hypersensitivity immune response.
9. describe a typical type IV hypersensitivity immune response.
celiac disease...
10. why is celiac disease not technically an allergic response?
11. what is the antigen in celiac disease?
12. describe the class switching mechanism in celiac disease.
13. what are microfold cells?
14. describe the activation of CD4 t cells in celiac disease.
15. when is a Th2 response employed in celiac's disease as opposed to a Th3 response?
other food allergies...
16. what are some characteristics of foods that commonly yield allergies?
17. describe how an allergic reaction to corn can lead to leaky gut.
18. what are some foods that typically create an allergic response?
answers
1. allergies, class switch to IgE
2. IgG against a surface protein
3. IgG against a soluble protein
4. t-cell mediated response
5. Th2 dominance is an allergic response, Th1 dominance is autoimmune disease.
6. type II hypersensitivity. glycosylated protein on RBC binds to penicillin, which is then opsinized by antibody, priming it for destruction by macrophages- resulting in hemolytic anemia.
7. because the immune response is against the penicillin, not the RBC’s- they are just a casualty.
8. antibody is released in response to soluble antigen; large antibody/antigen complexes form that can clog vessels. macrophages and neutrophils phagocytose complexes and create ROS which can damage the periphery.
9. the tuberculosis test is a typical type IV hypersensitivity response. purified protein derivative (PPD) is injected into the body- macrophages or dendritic cells ingest, carry to lymph nodes, and activate a Th1 response- T cells return to the infection site.
10. because there is no IgE class switch or a Th2 response- this is a Th1 response mediated by CD4 and CD8.
11. gliadin- resembles transglutaminase.
12. instead of being caused by a cytokine, it is caused by a the CD40/CD40L on B cell.
13. cells on the intestinal epithelium that transports whole antigen to the peyer’s patches.
14. dendritic cells or macrophages will ingest the wheat and produce one of two responses in T cells: if there is no co-stimulatory molecule, the T cell will go into the anergic state. if there is a co-stimulatory molecule (can be due to microflora entering from leaky gut caused by wheat), this causes IL-10 secretion and differentiation into Th3 cells, which secrete TGF beta, producing tolerance.
15. when IL-10 is secreted alongside IL-15.
16. high concentrations of hard to digest proteins, they make it far down the GI tract before being absorbed.
17. corn particles are ingested by macrophages in the peyer’s patches, and presented alongside CD86 (which is expressed for unknown reasons) to a CD4 t cell. the t cell differentiates into a Th2 cell by way of IL-10 and IL-15 cytokines, and secretes IL-4,5, and 13. IL-4 causes a class switch to IgE, which causes mast cells to degranulate and secrete TNF-alpha, which breaks down gut barrier and causes leaky gut.
18. dairy, soy, wheat, shellfish, nuts, corn, eggs, potatoes.
type II hypersensitivity is characterized by release of antibodies specific for molecules on cell surface. an example is the hypersensitivity to penicillin, which can occur when penicillin binds to a glycosylated protein on red blood cells. antibodies specific for the penicillin then bind to the redbloodcell/penicillin and are subsequently attacked by macrophages, resulting in hemolytic anemia (note that this is not an autoimmune response because the macrophages are targeting the penicillin primarily).
type III hypersensitivity is characterized by antibodies that are specific for soluble proteins- generally only occurs with high levels of soluble proteins. this often results in the formation of large antibody-soluble antigen complexes which can grow to block vessels or tubules. when this occurs macrophages and neutrophils are recruit to phagocytose the complexes and often damage the peripheral tissue by way of ROS production.
type IV hypersensitivity is a t-cell mediated response against antigen. the example given to us is celiac disease, which is a hypersensitivity to a peptide in wheat, gliadin. wheat is transported in from the lumen of the gut into the peyer's patches by microfold cells, where it can be ingested by macrophages and dendritic cell. these cells present the wheat peptide in an MHC to a CD4 t cell; if there is no co-stimulatory molecule expressed as well, this leads to a state of anergy and peripheral tolerance in the t cell. if there is co-stimulatory molecule expression (note that the increased microflora that enters the intestinal layers due to leaky gut can increase the likelihood of expression of co-stimulatory molecules) the CD4 t cell will be differentiated into a Th3 cell, which will proliferate and secrete TGF beta, resulting in a state of tolerance.
questions
different hypersensitivity mechanisms...
1. what is type I hypersensitivity characterized by?
2. what is type II hypersensitivity characterized by?
3. what is type III hypersensitivity characterized by?
4. what is type IV hypersensitivity characterized by?
5. what does an immune response dominated by Th2 result in? Th1?
6. what type of hypersensitivity is a penicillin hypersensitivity? describe the immune response.
7. why is a penicillin hypersensitivity not considered an autoimmune disease considering that red blood cells die in the process?
8. describe a typical type III hypersensitivity immune response.
9. describe a typical type IV hypersensitivity immune response.
celiac disease...
10. why is celiac disease not technically an allergic response?
11. what is the antigen in celiac disease?
12. describe the class switching mechanism in celiac disease.
13. what are microfold cells?
14. describe the activation of CD4 t cells in celiac disease.
15. when is a Th2 response employed in celiac's disease as opposed to a Th3 response?
other food allergies...
16. what are some characteristics of foods that commonly yield allergies?
17. describe how an allergic reaction to corn can lead to leaky gut.
18. what are some foods that typically create an allergic response?
answers
1. allergies, class switch to IgE
2. IgG against a surface protein
3. IgG against a soluble protein
4. t-cell mediated response
5. Th2 dominance is an allergic response, Th1 dominance is autoimmune disease.
6. type II hypersensitivity. glycosylated protein on RBC binds to penicillin, which is then opsinized by antibody, priming it for destruction by macrophages- resulting in hemolytic anemia.
7. because the immune response is against the penicillin, not the RBC’s- they are just a casualty.
8. antibody is released in response to soluble antigen; large antibody/antigen complexes form that can clog vessels. macrophages and neutrophils phagocytose complexes and create ROS which can damage the periphery.
9. the tuberculosis test is a typical type IV hypersensitivity response. purified protein derivative (PPD) is injected into the body- macrophages or dendritic cells ingest, carry to lymph nodes, and activate a Th1 response- T cells return to the infection site.
10. because there is no IgE class switch or a Th2 response- this is a Th1 response mediated by CD4 and CD8.
11. gliadin- resembles transglutaminase.
12. instead of being caused by a cytokine, it is caused by a the CD40/CD40L on B cell.
13. cells on the intestinal epithelium that transports whole antigen to the peyer’s patches.
14. dendritic cells or macrophages will ingest the wheat and produce one of two responses in T cells: if there is no co-stimulatory molecule, the T cell will go into the anergic state. if there is a co-stimulatory molecule (can be due to microflora entering from leaky gut caused by wheat), this causes IL-10 secretion and differentiation into Th3 cells, which secrete TGF beta, producing tolerance.
15. when IL-10 is secreted alongside IL-15.
16. high concentrations of hard to digest proteins, they make it far down the GI tract before being absorbed.
17. corn particles are ingested by macrophages in the peyer’s patches, and presented alongside CD86 (which is expressed for unknown reasons) to a CD4 t cell. the t cell differentiates into a Th2 cell by way of IL-10 and IL-15 cytokines, and secretes IL-4,5, and 13. IL-4 causes a class switch to IgE, which causes mast cells to degranulate and secrete TNF-alpha, which breaks down gut barrier and causes leaky gut.
18. dairy, soy, wheat, shellfish, nuts, corn, eggs, potatoes.
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