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Case 22: Megaloblastic Anemia and Mrs. H. Braelynne Morrow & Rebecca Noren Overview: 1. B12 and Folate a. How they are metabolized and absorbed b. Their importance in health and deficiencies 2. Assessment 3. Diagnosis 4. Interventions 5. Monitoring/Evaluation B12 & Folate Deficiencies Purpose of B12 - Vitamin B12 is a water soluble vitamin necessary for red blood cell formation, neurological function and DNA synthesis - Responsible for 3 processes in metabolism (1) Conversion of homocysteine to methionine (2) Conversion of methylmalonic acid (MMA) to succinyl CoA (3) Conversion of 5-methyltetrahydrofolate to tetrahydrofolate Physiology: Vitamin B12 Metabolism & Absorption 1. Foods containing vitamin B12 (cobalamin) are consumed. 2. 3. 4. 5. 6. HCL and protease break B12 from the protein structure. A B12-protein complex is formed Intrinsic factor (IF) is released from stomach lining. The B12 protein complex is solubilized and B12-IF complex forms. B12-IF complex solubilizes and B12 is absorbed into the blood and picked up by transcobalamin. 7. Then it is metabolized into 2 active forms (Methylcobalamin and Adenosylcobalamin) 8. These two forms act as coenzymes for Methionine synthase and Methylmalonic CoA Mutase 9. Biliary duct excretes B12 10. Ileum reabsorbs B12 11. B12 analogues (forms of B12 that can’t attach to B12 receptors) are excreted in feces Physiology: Vitamin B12 Metabolism & Absorption STOMACH: B-12 cleaved from food by HCl and proteases -B-12 binds haptocorrin (salivary B12 binding protein) -Intrinsic factor (IF) is released SMALL INTESTINE: B-12—haptocorrin complex solubilizes B-12—IF complex forms and enters cells through receptor-mediated endocytosis BLOOD: B12 is picked up by transcobalamin for transport BILIARY DUCT: B12 is excreted SMALL INTESTINE: B12 is reabsorbed RECTUM: B12-analogs excreted in feces Purpose of folate - Active folate (tetrahydrofolate) is used as methyl-tetrahydrofolate (mTHF) cofactor for enzymatic reactions in single carbon transfers. - These are necessary for protein, nucleic acid, neurotransmitter and phospholipid production - In a folate deficiency, substrates and metabolic intermediaries accumulate in the cell which can have negative consequences Physiology: Folate Metabolism & Absorption 2 3 1 http://www.humpath.com/spip.php?article13556 How B12 and folate deficiencies are related In order to metabolize folate to its active form, vitamin B12 is needed. If a known vitamin B12 deficiency is present, a folate deficiency can occur. This is known as the folate trap. DeBiasse, 2014 Signs & Symptoms of Deficiency Folate Deficiency: - Clinical symptoms: - Macrocytic anemia - Physical symptoms: - Inflammation of the tongue, diarrhea, poor growth, neural tube defects, fatigue, pale skin, irritability B12 Deficiency: - Clinical symptoms: - Pernicious anemia, macrocytic anemia - Physical symptoms: - Nerve damage, weakness, tiredness, lightheadedness, heart palpitations, shortness of breath, pale skin, constipation, numbness, tingling, muscle weakness, memory loss, depression A: Assessment Overview of Patient History - Patient: Mrs. H - 72 YOWF - Over the last 6 months, she has experienced fatigue and parasthesias in her hands and feet. - CC: “My doctor felt that my blood work needed a second opinion”. - Physician admitted her due to general pancytopenia - Physician ordered a hematology consult at the University Hospital - All vital signs were stable upon admission - Pancytopenia: Reduction in WBC, RBC, and platelets. - Parasthesias: Numbness and tingling Nelms, 2014 Past Medical History - Medical History - Vertebral compression fracture L1-L2 secondary to osteoporosis - Osteoarthritis - Surgical History - S/p gastric bypass (Roux-en-Y) x 25 years ago Nelms, 2014 Medications - Medications at home: - Fosamax 10 mg 1xd - Celebrex 200mg 1xd - Calcium 800mg 2xd - Vitamin D 800IU Nelms, 2014 Medication Implications Fosamax: prescription medication used to prevent or help treat osteoporosis - Fosamax is a bisphosphate that is a bone-resorption inhibitor - CAUTION: Caffeine especially in coffee, cocoa and tea, orange juice and mineral water decrease the absorption of Fosamax -Taking Fosamax and non-steroidal anti-inflammatory drug together can cause GI irritation and possible bleeding Celebrex: non-steroidal anti-inflammatory drug -Increased risk of panctyopenia -Non-steroidal anti-inflammatory drugs not preferred in those who have had gastric bypass due to stomach irritation and potential bleeding Physician’s Admission Orders and Assessment Orders: Assessment - - Lab work up - Labs WNL: - Chemistry, coagulation, hematology manual difference - Abnormal labs: - Hematology Vital signs & I&O: Every 8 hours Diet: regular Activity: ad lib Scheduled medications: - Continue home medications - Colace (docusate) 100mg po two times daily prn if no bowel movement - Milk of Magnesia (MOM) 30mL po daily prn - Results from lab indicate: - Low folate - Low B12 - Elevated MMA - Normal Hcy consistent with mixed deficiency - Bone marrow aspirate consistent with megaloblastic anemia Nelms, 2014 Diagnostic Workup for Anemias Test Anti-intrinsic factor antibodies Indication Antibodies formed against parietal cells are similar to decreased intrinsic factor activity and therefore suggestive of B12 deficiency. Mrs. H: Negative results, so, no autoantibodies. Helps rule out pernicious anemia. Antiparietal cell antibodies Methylmalonic acid Used to diagnose pernicious anemia. Positive test results may be due to atrophic gastritis, diabetes, a gastric ulcer, pernicious anemia or thyroid disease. Mrs. H: Negative results, so, no autoantibodies. Helps rule out pernicious anemia. Helps determine B12 status. Elevated MMA indicates metabolic change specific to vitamin B12 deficiency. Mrs. H: Elevated results. Indicates B12 deficiency. Homocysteine When elevated can suggest B12 deficiency. Important to note serum B12 concentration not always accurate reflection of intracellular levels and therefore homocysteine levels can be measured. Can be influenced by decreased B6 or folate levels. Mrs. H: Normal levels. Schilling Test Determines ability to absorb Vitamin B12 properly and if pernicious anemia, megaloblastic anemia or anemia of B12 deficiency is present. It is a staged test, and if first stage is abnormal continue on to 2, 3, and 4. Mrs. H: Ordered. Laboratory Data Lab Mrs. H’s Value Normal Indication Mean Cell Volume 130 um3 80-96 um3 Large RBCs associated with megaloblastic anemia. Mean Cell Hemoglobin 34pg 26-32pg Less RBCs means more Hgb/cell. Indicates macrocytic anemia. Mean Cell Hemoglobin Content 38 g/dL 31.5-36g/dL High d/t high Hgb concentration in RBCs d/t B12 deficiency and larger concentrations w/in blood. RBC Distribution 17.8% 11.6-16.5% High d/t high RBC concentration d/t enlargement in B12 deficiency. Platelet Count 135mm3 140-440mm3 Low d/t low production from bone marrow d/t B12 and folate deficiencies. Vitamin B12 11ng/dL 24.4-100ng/dL Low d/t malabsorption. Folate 3.2ng/dL 5-25ng/dL Low d/t b12 deficiency and trapped stores. MMA 0.75mmol/L 0.08-0.56mmol/L An intermediate in FFA metabolism, so when B12 deficient, MMA increases. Normal levels are seen in folate deficiency. Indication of low B12. Nelms, 2014 Physician’s Diagnosis & Plan Dx: B12 and folate deficiency with megaloblastic anemia secondary to gastric bypass and malabsorption combined with probable deficient dietary intake. Plan: 1000ug cyanocobalamin IM; 5000ug folate. Discharge and follow weekly for additional B12 injections, folate supplementation, and repeat laboratory values. Nutrition consult. Nelms, 2014 Admission Nutrition Note - Meal type: Regular Fluid Requirement: 1800-2000 mL History: - Patient states she lost over 150 lbs after gastric bypass (Rouxen-Y) - Since then, her weight has fluctuated between 150-175 lbs. - Weight stable at 165 lbs for last 5 years - States she mostly eats all foods but most frequently eats fruits and vegetables- some grains. Rarely eats meat but does like chicken, eggs and dairy. Nelms, 2014 24-hr Dietary Recall Breakfast: 2 slices cheddar cheese melted on 2 slices English muffin, coffee with half and half, 1 cup cantaloupe Lunch: 1 cup broccoli and cheese soup, ½ cup chicken salad with 12 whole-wheat crackers, iced tea with lemon and artificial sweetener Dinner: 2 cup fettuccine alfredo with chicken, 1 cup romaine lettuce with tomatoes, iced tea Snack: 1 cup strawberry ice cream Calories eaten: 1821 kcal Protein: 96 grams Nelms, 2014 Nutrients Report from 24-hour recall using SuperTracker Nutrients Target Average Eaten Status Vitamin B12 2.4 µg 2.5 µg OK Folate 400 µg DFE 464 µg DFE OK Initial Calculations Height: 5’1’’ = 1.54m Weight: 165 lbs BMI: wt(kg)/m2 = 75kg/2.4025 =31kg/m2 %UBW: current/usual x 100 = (165/165) x 100 = 100% IBW: 100 + 5 =105 lbs %IBW: Actual/ideal x 100 = (165/105) x 100 = 157% Assessment: According to BMI, Mrs. H is considered Class 1 obese. She has had neither severe nor significant weight changes for the past 5 years. Calorie & Protein Goals Calorie Goals: - 20kcal/kg =20 kcal x 75g= 1500 kcal - MSJ REE= 10(75) + 6.25 (154.94) -5(72) =750 + 968.375-360-161 =1197.375=1197kcal/day Protein Goals: - 1g/kg 1x75kg= 75g protein - 20%kcal =0.20x1197=239.4kcal/4 grams/kcal=59.85= 60 grams protein Obesity & Elderly Considerations Calorie Consideration -BMI: 31kg/m2 -Calories consumed from 24 hour food recall: ~1821 kcal -Calorie recommendation: ~1200-1300 kcal Elderly Protein Consideration - Protein for elderly ~ 1-1.3g/kg - Protein consumed from 24 hour food recall: 96 grams - Protein recommendation: 75g-98g/kg Nutritional Status 1. Although her diet consists of enough folate and B12, only 50% normally is absorbed. 2. Her diet is high in processed foods. 3. Her diet is high in calories for her age (she is still considered obese). D: Diagnosis Causes of B12 and Folate Deficiency 1. Gastric Bypass - Less surface area - Decreased or absent product of IF - Supplementation needed 2. Age - Over the age of 65, stomach acid production decreases 3. Medications - Fosamax and Celebrex 4. Diet - Diet contains adequate levels of B12 and Folate, but only 50% of vitamins are absorbed in normal gastric function ADIME Note: Diagnosis Nutrition Dx: Impaired nutrient utilization related to gastric bypass and aging as evidenced by fatigue, parasthesias, pale skin, decreased serum folate (3.2ng/dL), and decreased serum vitamin B12 (11.1ng/dL). I: Intervention Interventions: (1) Increase dietary sources of folate & B12 1. Increase intake of food sources of B12 such as yogurt, meats/poultry, organ meats, seafood, and fortified cereal or bread 2. Increase intake of folate food sources - Leafy green vegetables such as asparagus, cooked spinach, cooked peas, or romaine lettuce Folate B12 Interventions: (2) Supplementation Suggestions Physician’s Recommendations: - 1000ug cyanocobalamin IM - 5,000ug folate RD Recommendations: - 350-600 ug cyanocobalamin - Monthly IM injections of up to 1,000 ug cyanocobalamin - 5,000 ug Folate Xanthakos, 2009 Helpful Apps - B12 Deficiency App - For patients who have received a B12 deficiency diagnosis. - Allows individuals to track medications and symptoms. - BariApps - Patients can call their physicians, ask dietitians their questions, track their journey, find recipes, set reminders to take vitamins/supplements, access a support group, keep time intervals between meals and fluids, make appointments, track exercise, and more - For both pre and post-surgery Forums - B12 Deficiency Website/Forum - All-encompassing site which provides information regarding B12 deficiency, who is at risk, symptoms, testing, treatments and more - Includes a blog and Facebook page for patients to connect with others - B12 Awareness Website/Forum - Provides information regarding B12 deficiency, other related disorders and various tools for press, movies, books and associated foundation - BariatricPal Website/Forum - Appears useful and motivating for pre and post-bariatric surgery patients. There are areas to share success stories, find a surgeon, find a support group, different forum threads, and more. M/E: Monitoring & Evaluation Monitoring/Evaluation 1. Check abnormal lab values 1x/mo -Transcobalamin -Serum homocysteine -Serum folate levels 2. Measure weight 1x/mo. 3. Follow up with food recalls (every month until anemia is resolved) to determine if more B12 and folate sources have been included. 4. Additionally check food records to see if patient is complying with additional fruit and vegetable intake as well as cereal grains. Questions? Wrap-Up - B12 deficiency is common in gastric bypass patients d/t low IF production - Elderly have hypochlorohydria which is important for enzyme activation of proteases and B12 absorption - To metabolize folate to its active form, vitamin B12 is needed - Case of Mrs. H: Nutrition DX: Impaired nutrient utilization related to gastric bypass and aging as evidenced by fatigue, parasthesias, pale skin, decreased serum folate (3.2ng/dL), and decreased serum vitamin B12 (11.1ng/dL). - Good sources of folate and B12 Folate: lentils, pinto beans, garbanzo beans, navy beans, black beans, liver, and asparagus B12: Liver (especially beef), clams, oysters, salmon, and sardines - Supplementation: - 350-600 ug cyanocobalamin - Monthly IM injections of up to 1,000 ug cyanocobalamin - 5,000 ug Folate