Term
| how can chronic diarrhea (infectious/noninfectious) cause malabsorption? |
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Definition
| transport of feces through the bowel is too fast - leading to defective absorption of fats (steatorrhea)/vitamins/proteins/carbohydrates/electrolytes/minerals/water (serious dehydration). this can affect many different organ systems: decreased Ca++ absorption causes osteopenia/osteoporosis/tetany, decreased vit K absorption: bleeding disorders, decreased iron absorption: anemia. overall pts w/chronic diarrhea tend to have weight loss, fatigue, and anemia |
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Term
| what is steatorrhea characterized by? |
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Definition
| high fat loss in feces, characterized by a particularly foul smell and floating properties |
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Term
| how do intraluminal digestion disturbances cause malabsorption? |
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Definition
| stool/chyme gets into the lumen, but there is a problem breaking these substances down into particles small enough for absorption |
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Term
| how do terminal digestion disturbances cause malabsorption? |
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Definition
| a terminal digestion disturbance occurs with defective hydrolysis of carbohydrates/proteins in the small intestine |
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Term
| how do transepithelial transport disturbances cause malabsorption? |
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Definition
| nutrients/fluid/electrolytes are ready for transport, but there is something inhibiting transport across the SI epithelium. specifically: lymphatic transport disturbances occur when absorbed lipids cannot be transported -> leads to steatorrhea |
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Term
| what is a disease of malabsorption covered often in the media? |
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Definition
| celiac disease - which is a genetic auto-immune mediated sensitivity to gluten (a protein found in barley, rye, and wheat) |
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Term
| what is the specific form of gluten which is problematic? what does it do? |
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Definition
| the alcohol-soluble fraction of gluten: *gliadin, peptides of which induce proliferation of *CD8 intraepithelial lymphocytes inducing NK cells to injure enterocytes. gliadin can also induce *T cells to cause the characteristic mucosal pathology. |
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Term
| what are the major genes involved with celiac disease? |
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Definition
| HLA-DQ2, DQ8 (can be associated w/ other types of autoimmune diseases like sjogren’s syndrome and others) |
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Term
| what serum antibodies have been identified as involved with celiac disease? |
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Definition
| IgA class antitissue transglutaminase (antitTG), antiendomysial antibody (EMA), and antigliadin antibodies (AGA) |
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Term
| what happens to the villi in celiac disease? |
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Definition
| villus atrophy (decreased surface area), crypt elongation, infiltration of the epithelium w/intraepithelial lymphocytes, and increased mitosis of enterocytes |
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Term
| what is the specific interaction between enterocytes and lymphocytes involving MIC-A in celiac disease? |
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Definition
| some enterocytes express MIC-A, which activates T-cells who then increase *IL-15 production. release of IL-15 induces NK protein binding to the MIC-A, which then stimulates T-cell mediated destruction of the enterocytes |
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Term
| do celiacs have higher levels of MIC-A expression? |
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Definition
| yes, during their celiac sprue |
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Term
| what is the specific interaction between enterocytes and lymphocytes involving gliadin in celiac disease? |
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Definition
| once the cells have been damaged via the MIC-A pathway, gliadin makes its way into enterocytes and is deaminated by tissue transglutaminase. this allows for binging of APCs (particularly the HLA alleles on the APCs) - this allows APCs to present antigen to T cells, who then produce IFN and stimulate B cells, who become plasma cells |
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Term
| what are some other diseases associated with celiac (may be the initial presenting chief complaint )? |
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Definition
| fam hx of celiac, autoimmune diseases, type I diabetes, thyroiditis, IgA deficiency, and genetic syndromes such as downs/turners |
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Term
| what are clinical features of celiac disease? |
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Definition
| anemia, osteoporosis, neurological problems (if they lack vitamins or Ca++), chronic diarrhea, weight loss (consistent finding), *dermatitis herpetiformis (itchy blistering skin disease - often on back)*, lymphocytic gastritis, and lymphocytic colitis |
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Term
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Definition
| yes, some pts aren't diagnosed until 20s-30s |
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Term
| where is the CELIAC1 gene? |
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Definition
|
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Term
| where is the CELIAC2 gene? |
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Definition
|
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Term
| where is the CELIAC3 gene? |
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Definition
| on chr 2q33 (which contains the T cell regulatory genes CD28, CTLA4, and ICOS) |
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Term
| where is the CELIAC4 gene? |
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Definition
| the myosin IXB gene, MYO9XB on chr 19p13.1 |
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Term
| what is the classic celiac disease presentation (in younger children)? |
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Definition
| failure to thrive (not meeting developmental milestones of growth/weight/height), diarrhea, abdominal distention (third-spacing due to protein loss), and developmental delay = presenting weeks-months after introduction of weaning foods |
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Term
| what is the classic celiac disease presentation (in older children)? |
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Definition
| older children may present with short stature or dental enamel problems |
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Term
| what is the classic celiac disease presentation (in adults)? |
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Definition
| diarrhea, constipation, flatus (buildup of gas from not being able to digest properly), belching, anemia, weight loss, and vitamin deficiencies |
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Term
| what might be included in an atypical celiac disease presentation? |
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Definition
| few/no GI symptoms, more extraintestinal symptoms, iron deficiency, osteoporosis, short stature, and infertility (symptoms are milder than classic form) |
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Term
| what is silent celiac disease? |
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Definition
| asymptomatic celiac disease, which is sometimes uncovered in screening of a confirmed celiac's family. these pts are still at risk for developing complications. |
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Term
| what is the marsh I level of celiac disease? |
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Definition
| histologically, there is marked infiltration of villous epithelium by lymphocytes |
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Term
| what is the marsh II level of celiac disease? |
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Definition
| histologically, there is intraepithelial lymphocytosis and elongation/branching of crypts w/increased epithelial cells |
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Term
| what is the marsh III level of celiac disease? |
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Definition
| intraepithelial lymphocytosis, crypthyperplasia, and villous atrophy |
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Term
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Definition
| malabsorption which becomes apparent w/in a few days or weeks of an acute enteric diarrheal infection. it is unrelated to gluten sensitivity and is usually seen in the tropics. |
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Term
| what pathogen might tropical sprue be related to? |
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Definition
| ETEC - therefore treatable by antibx |
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Term
| what forms of tx is tropical sprue usually receptive to? |
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Definition
| folic acid, vit B12, and tetracycline |
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Term
| how does tropical sprue present histologically? |
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Definition
| partial villous atrophy w/lymphocytes. total villous atrophy is uncommon (similar to marsh I in celiac sprue) |
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Term
| what is autoimmune enteropathy? |
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Definition
| an X-linked disorder characterized by severe, persistent diarrhea, and autoimmune disease seen mainly in young children. |
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Term
| what is the genetic syndrome associated with autoimmune enteropathy? |
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Definition
| IPEX: immune dysregulation, polyendocrinopathy, enteropathy, and X linkage. this is due to a *germline mutation in the FOXP3 gene on the X chromosome*. this associated with defective T cell regulation who develop antibodies against enterocytes and goblet cells (also possibly parietal cells/islet cells). |
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Term
| how does autoimmune enteropathy compare to celiac sprue? |
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Definition
| they can appear similar, both involve T cell disregulation - but pts w/autoimmune enteropathy don't have the same severity of lymphocytosis in the epithelium and you will not see antibodes to gliadin. |
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Term
| what characterizes a lactase (disaccharidase) deficiency? |
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Definition
| this results in problems digesting milk products and can be congenital or aquired. it is due to a biochemical defect where lactase is not present onf the brush border of the villi. histology is usually unremarkable. |
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Term
| how does a congenital lactase deficiency occur? |
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Definition
| in this, there is a mutation coding for lactase - and exposure to milk products causes explosive diarrhea |
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Term
| how does an acquired lactase deficiency occur? |
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Definition
| the lactase gene expression is downregulated and the disease presents after childhood, resulting in abdominal fullness, diarrhea, and flatulence |
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Term
| what is abetalipoproteinemia? |
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Definition
| a rare autosomal recessive disease resulting in the inability to secrete triglyceride rich lipoproteins due to a mutation in the *microsomal trigylceride transfer protein (MTP) - which catalyzes transport of triglycerides, cholesterol esters, and phospholipids. monoglycerides cannot be assembled into chylomicrons and triglycerides can accumulate in epithelial cells. |
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Term
| what is seen histologically in small intestinal epithelial cells after fatty meals in pts with abetalipoproteinemia? |
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Definition
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Term
| how do pts with abetalipoproteinemia present? |
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Definition
| in infancy: failure to thrive and steatorrhea |
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Term
| what effect do the lipid membrane defects due to abetalipoproteinemia have on RBCs? |
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Definition
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Term
| what kind of nutrient deficiency would be seen in pts with abetalipoproteinemia? |
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Definition
| fat soluble vitamin deficiency - can lead to musculoskeletal, vision, clotting, and anti-oxidant problems |
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Term
| what is whipple's disease? who does it affect? |
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Definition
| accumulation of macrophages infected with bacilli - *tropheryma whippelii in the small intestine mucosa. these macrophages resemble those seen in the CNS, lymph nodes, and spleen and the condition can lead to malabsorption with *CNS symptoms, polyarthritis and hyperpigmentation*. it will usually affect white males 30-40 years old |
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Term
| what are some hematopoietic consequences of malabsorption? |
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Definition
| anemia, bleeding disorders |
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Term
| what are some musculoskeletal consequences of malabsorption? |
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Definition
|
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Term
| what are some endocrine consequences of malabsorption? |
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Definition
| amenorrhea and infertility |
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Term
| what are dermatologic consequences of malabsorption? |
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Definition
| purpura, petechiae (clotting abnormalities), and dermatitis (collagen formation problems) |
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Term
| what are some neural consequences of malabsorption? |
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Definition
| peripheral neuropathy (lack of vit D) |
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