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11 - Gastrointestinal Disease
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Congenital Lactase Deficiency
- absence of lactase activity at birth
- infants with this condition who're breastfed will get diarrhea from the milk
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Congenital Lactase Intolerance
- a defect in absorption, NOT a defect of digestion
- lactose is usually absorbed in the intestine but in THIS case it's absorbed in the stomach & circulates in the blood stream as lactose which is abnormal & problematic
- not usually done & can cause multi-organ damage or dysfunction
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Hypolactasia
- partial or complete loss of brush border lactase activity
- acquired or congenital - acquired is more common
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Lactase Nonpersistence (LNP)
- ACQUIRED Hypolactasia
- Primary: autosomal recessive genetically programmed loss of lactase gene expression & activity that occurs after weaning; often starts at 3-5 years
- Secondary: caused by disease, injury, drugs, radiation,
- surgery, or infection
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Which is permanent & which is reversible, primary or secondary Acquired Hypolactasia (LNP)?
- PRIMARY is permanent because it's caused by a genetic mutation
- secondary is reversible after whatever stimulus is causing the brush border impairment is removed
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What type of people tend to have more lactase (preserved)?
- Primary Acquired Lactase Nonpersistence is genetically based
- Caucasians/Europeans have the most lactase & therefore the greatest ability to digest lactose
- Asians & African Americans tend to have higher rates of primary LNP which can cause lactose intolerance
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Lactose Intolerance
- LNP causes lactose maldigestion or lactose intolerance if SYMPTOMS occur
- symptoms result from:
- osmotic load, where unabsorbed lactose leads to water influx into SI
- cramping, distention
- lactose fermentation
- abdominal pain
- increased motility
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What do colonic bacteria do to (undigested) lactose?
- they can ferment it resulting in
- 1) short chain FAs: these are absorbed by colonocytes but if unabsorbed cause DIARRHEA
- 2) Gas: 50% H2 + methane & CO2 which causes cramps, flatus, & increased motility
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What determines the severity of lactose intolerance symptoms?
- Degree of LNP: the more enzyme, the fewer symptoms
- Lactose load: amount ingested, rate of delivery to the SI, rate of gastric emptying; a mixed meal might slow release of lactose in intestines, help body keep up with lactase production
- Ability to ferment + absorb short chain FAs: flatus still produced in that situation
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Dietary Approaches to Lactose Intolerance
- 1. avoiding lactose-containing foods
- 2. limit RATE of lactose delivery to small intestine
- 3. eat β-galactosidase rich food (YOGURT)
- 4. add β-galactosidase to food
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What might be a concern for people avoiding lactose-containing foods due to lactose intolerance?
- that they might not get enough Calcium or Vitamin D because most people depend on dairy products for those micronutrients
- deficiencies of these puts people at risk for osteoporosis
- it is possible to get them outside of dairy, or one could eat dairy with less lactose like hard cheeses over soft ones (bacteria digest the lactose during the aging process)
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How can a person limit RATE of lactose delivery to small intestine?
- by having a mixed meal
- eg. fat slows digestion from the stomach
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β-galactosidase (β-gal)
- a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides (eg. lactose) into monosaccharides
- enzyme can be found in bacteria which itself is found in different foods (yogurt)
- bacteria are lysed in the upper GI tract upon food ingestion, liberating the β-galactosidase which can digest lactose
- can also take a capful of β-galactosidase or have β-galactosidase-enriched food (lactaid milk)
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Celiac Disease (Celiac Sprue)
- an immune-mediated (IgA) response to dietary gluten
- it's more common in people of European descent
- it's UNDER diagnosed (1/133 people in the US)
- a person is at increased risk for Celiac's if a 1st degree relative has the disease (prevalence goes to 1/22)
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What other types of diseases is Celiac's associated with?
- AUTOIMMUNE diseases
- type 1 Diabetes Mellitus
- thyroid disease liver disease
- selective IgA deficiency
- inflammatory bowel disease (IBS)
- eosinophilic esophagitis
- down syndrome…
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Gluten
- a protein found in wheat, barley, rye, possibly oats, many medications, & hygiene products, where it's used as a filter/preservative
- ingestion of gluten if intolerant leads to destruction of the small intestine mucosa
- this manifests as diarrhea, bloating, nutrient malabsorption, & sometimes dermatitis herpetiformis, an itchy skin rash
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What is the hypothesis behind gluten's activation of an immune response against the small intestine mucosa?
- 1. indigestible fragments of gluten induce enterocytes to release zonulin → LOOSENS tight junctions between mucosal cells
- 2. gluten may move through now opened spaces between cells & accumulate underneath
- 3. enterocytes secrete IL-15 in response to deposited gluten → intraepithelial leukocytes squeeze through mucosa to target area
- 4. tissue transglutaminase (TTG) modifies the gluten, which is now picked up by APCs, presented to T cells, initiating an immune response
- 5. T cell activation occurs, B cells make Ig's to gluten, & damage mucosal enterocytes in the destruction process
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How is Celiac Disease diagnosed?
- by measuring tissue transglutaminase (TTG), the enzyme that modifies gluten before it's presented in MHC class II molecules, activating an immune response
- a tissue biopsy is often collected for confirmation
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How is Celiac Disease managed?
- Consult w/ a skilled dietician
- Educate about the disease
- Lifelong adherence to a gluten-free diet*
- Identify + treat nutritional deficiencies
- Access should be provided to advocacy groups
- Continuous long-term follow up (by a multidisciplinary team)
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Why might someone not respond to a gluten-free diet?
- 1. could be blatant non-compliance to the diet
- 2. accidental ingestion of gluten
- 3. complete misdiagnosis
- 4. a concurrent disorder: another condition affecting GI tract (eg. cholitis)
- 5. refractory sprue: when someone never improves on a gluten-free diet
- 6. something completely unrelated (eg. ulcerative jejunitis, intestinal lymphoma)
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Why is it important to follow a gluten-free diet when diagnosed with Celiac Disease?
- because if you don't that can result in intestinal damage which causes malabsorption
- manifests as diarrhea/steatorrhea, weight loss, vitamin deficiency, & mineral deficiency
- *in some cases unexplained IRON deficiency may be the first sign of Celiac Disease
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What foods you might not expect to have gluten contain gluten?
- grain & many grain products
- grain vinegar - found in most condiments
- food starches added or dusted on many foods
- beer & grain alcohol
- medications
- hygiene products
- *because gluten-free diets can be difficult to follow, can focus on what a patient CAN have as opposed to what they can't (especially if they've had weight loss)
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Gluten-free Labeling
- 1. cannot contain wheat, rye, barley, or crossbreeds of these grains
- 2. any ingredient derived from these grains must have been processed to remove gluten
- 4. cannot contain 20 ppm or more gluten
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Why is it important for a person with Celiac Disease to follow a gluten-free diet even if they don't have serious symptoms?
- because damage to the GI tract will put them & risk for micronutrient deficiencies & the associated conditions that can result
- Osteoporosis ~ vitamin D + Calcium [also vitamin K]
- Lactose Intolerance ~ example of secondary persistence
- Small Bowel Lymphoma ~ related to intestine damage or immunosuppression treatment involved
- Pregnancy Complications ~ women w/ unmanaged Celiac's have poor pregnancy outcomes or trouble getting pregnant
- Stunting in children ~ if a child isn't absorbing nutrients they're not going to grow
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Oral Rehydration Solution
- in some areas of the world children don't have a clean water supply
- as a result many get infectious diarrhea & die from dehydration
- eg. cholera toxin destroys GI tract & causes net pooling + secretion of water in GI tract lumen
- however transporters are still functional, so providing a sodium/glucose solution causes water to passively follow sodium into the circulatory system to maintain osmolality
- can pull fluid in across basolateral membrane & hydrate individual using such a solution
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Pancreatitis
- inflammation of the pancreas
- may be acute or chronic (chronic presents with more long-term abdominal pain; smoking contributes to both types)
acute symptoms: sudden onset abdominal pain & elevated serum amylase and lipase
most common causes: Gallstones & Alcohol
- • Abdominal injury or surgery
- • Cystic fibrosis
- • Genetic predisposition
- • Hypercalcemia
- • Hyperparathyroidism
- • Hypertriglyceridemia
- • Infection
- • Medications
- • Pancreatic cancer
- • Smoking
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Triglyceride-induced Pancreatitis
- not a particularly common type of pancreatitis however it can be avoided by taking cautionary nutritional measures
- controlling a persons obesity, diabetes, alcohol intake, or certain hyperlipoproteinemias can help prevent this type of pancreatitis
- there's also a risk of high triglycerides during pregnancy
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Acute Pancreatitis
- most commonly caused by alcohol & gallstones
- for a mild/moderate case: nil per os (NPO) + IV fluids for up to a week
- for a severe case: enteral nutrition to stimulate the GI a little, as failure to do so may worsen the severity of disease
- VERY severe cases: parenteral nutrition in to prevent further malnutrition
- *fat in the diet produces the most pain b/c without pancreatic lipase fat digestion doesn't occur
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Chronic Pancreatitis
- permanent impairment of the pancreas
- can lead to exocrine dysfunction - no production of pancreatic enzymes
- this leads to fat malabsorption which can lead to Steatorrhea, Weight loss (afraid to eat b/c painful), or Fat soluble vitamin deficiencies
- originally caused by alcohol, familial predisposition, a juvenile form limited to tropical areas of the developing world, or an unknown cause (idiopathic)
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How can you treat Chronic Pancreatitis?
- pancreatic enzyme replacement therapy
- large pills that need to be consumed when something with fat is eaten
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Constipation
- less than or 3 stools per week
- is associated with inadequate fiber intake, dehydration, physical inactivity, medications, & intestinal disease
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Diverticular Disease
- high intracolonic pressure can cause colonic outpouchings, called DiverticulOSIS
- if in addition you have poor intestinal transit, things such as food, stool, or bacteria can get stuck in the outpouchings
- DiverticuLITIS: infection & inflammation due to impaction of stool or food particle in colonic outpouchings
*diverticular disease is managed with a HIGH FIBER diet; in societies with a HIGH fiber intake, there's a LOW prevalence of diverticular disease
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How does a high fiber diet help manage diverticular disease?
- 1. decreases how long it takes for food to move from mouth to anus (Transit Time)
- 2. causes stool bulking, making it easier for peristaltic action to move it along
- 3. decreases intracolonic pressure → less diverticulosis
such a diet should consist of increased fruit, vegetables, & whole grain, adequate hydration, and possibly fiber supplements
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