Case 22 Megaloblastic Anemia and Mrs H Braelynne

Case 22: Megaloblastic Anemia and Mrs. H. Braelynne Morrow & Rebecca Noren

Overview: 1. B 12 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

B 12 & Folate Deficiencies

Purpose of B 12 - Vitamin B 12 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 Co. A (3) Conversion of 5 -methyltetrahydrofolate to tetrahydrofolate

Physiology: Vitamin B 12 Metabolism & Absorption 1. Foods containing vitamin B 12 (cobalamin) are consumed. 2. 3. 4. 5. 6. HCL and protease break B 12 from the protein structure. A B 12 -protein complex is formed Intrinsic factor (IF) is released from stomach lining. The B 12 protein complex is solubilized and B 12 -IF complex forms. B 12 -IF complex solubilizes and B 12 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 Co. A Mutase 9. Biliary duct excretes B 12 10. Ileum reabsorbs B 12 11. B 12 analogues (forms of B 12 that can’t attach to B 12 receptors) are excreted in feces

Physiology: Vitamin B 12 Metabolism & Absorption STOMACH: B-12 cleaved from food by HCl and proteases -B-12 binds haptocorrin (salivary B 12 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: B 12 is picked up by transcobalamin for transport BILIARY DUCT: B 12 is excreted SMALL INTESTINE: B 12 is reabsorbed RECTUM: B 12 -analogs excreted in feces

Purpose of folate - Active folate (tetrahydrofolate) is used as methyl-tetrahydrofolate (m. THF) 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 1 3 http: //www. humpath. com/spip. php? article 13556

How B 12 and folate deficiencies are related In order to metabolize folate to its active form, vitamin B 12 is needed. If a known vitamin B 12 deficiency is present, a folate deficiency can occur. This is known as the folate trap.

De. Biasse, 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 B 12 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 - Vertebral compression fracture L 1 -L 2 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 1 xd - Celebrex 200 mg 1 xd - Calcium 800 mg 2 xd - Vitamin D 800 IU 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: - - 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) 100 mg po two times daily prn if no bowel movement - Milk of Magnesia (MOM) 30 m. L po daily prn - Results from lab indicate: - Low folate - Low B 12 - 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 Antiparietal cell antibodies Methylmalonic acid Indication Antibodies formed against parietal cells are similar to decreased intrinsic factor activity and therefore suggestive of B 12 deficiency. Mrs. H: Negative results, so, no autoantibodies. Helps rule out pernicious anemia. 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 B 12 status. Elevated MMA indicates metabolic change specific to vitamin B 12 deficiency. Mrs. H: Elevated results. Indicates B 12 deficiency. Homocysteine When elevated can suggest B 12 deficiency. Important to note serum B 12 concentration not always accurate reflection of intracellular levels and therefore homocysteine levels can be measured. Can be influenced by decreased B 6 or folate levels. Mrs. H: Normal levels. Schilling Test Determines ability to absorb Vitamin B 12 properly and if pernicious anemia, megaloblastic anemia or anemia of B 12 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 um 3 80 -96 um 3 Large RBCs associated with megaloblastic anemia. Mean Cell Hemoglobin 34 pg 26 -32 pg Less RBCs means more Hgb/cell. Indicates macrocytic anemia. Mean Cell Hemoglobin Content 38 g/d. L 31. 5 -36 g/d. L High d/t high Hgb concentration in RBCs d/t B 12 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 B 12 deficiency. Platelet Count 135 mm 3 140 -440 mm 3 Low d/t low production from bone marrow d/t B 12 and folate deficiencies. Vitamin B 12 11 ng/d. L 24. 4 -100 ng/d. L Low d/t malabsorption. Folate 3. 2 ng/d. L 5 -25 ng/d. L Low d/t b 12 deficiency and trapped stores. MMA 0. 75 mmol/L 0. 08 -0. 56 mmol/L An intermediate in FFA metabolism, so when B 12 deficient, MMA increases. Normal levels are seen in folate deficiency. Indication of low B 12. Nelms, 2014

Physician’s Diagnosis & Plan Dx: B 12 and folate deficiency with megaloblastic anemia secondary to gastric bypass and malabsorption combined with probable deficient dietary intake. Plan: 1000 ug cyanocobalamin IM; 5000 ug folate. Discharge and follow weekly for additional B 12 injections, folate supplementation, and repeat laboratory values. Nutrition consult. Nelms, 2014

Admission Nutrition Note - Meal type: Regular Fluid Requirement: 1800 -2000 m. L 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 Super. Tracker Nutrients Target Average Eaten Status Vitamin B 12 2. 4 µg 2. 5 µg OK Folate 400 µg DFE 464 µg DFE OK

Initial Calculations Height: 5’ 1’’ = 1. 54 m Weight: 165 lbs BMI: wt(kg)/m 2 = 75 kg/2. 4025 =31 kg/m 2 %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: - 20 kcal/kg =20 kcal x 75 g= 1500 kcal - MSJ REE= 10(75) + 6. 25 (154. 94) -5(72) =750 + 968. 375 -360 -161 =1197. 375=1197 kcal/day Protein Goals: - 1 g/kg 1 x 75 kg= 75 g protein - 20%kcal =0. 20 x 1197=239. 4 kcal/4 grams/kcal=59. 85= 60 grams protein

Obesity & Elderly Considerations Calorie Consideration -BMI: 31 kg/m 2 -Calories consumed from 24 hour food recall: ~1821 kcal -Calorie recommendation: ~1200 -1300 kcal Elderly Protein Consideration - Protein for elderly ~ 1 -1. 3 g/kg - Protein consumed from 24 hour food recall: 96 grams - Protein recommendation: 75 g-98 g/kg

Nutritional Status 1. Although her diet consists of enough folate and B 12, 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 B 12 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 B 12 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. 2 ng/d. L), and decreased serum vitamin B 12 (11. 1 ng/d. L).

I: Intervention

Interventions: (1) Increase dietary sources of folate & B 12 1. Increase intake of food sources of B 12 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 B 12

Interventions: (2) Supplementation Suggestions Physician’s Recommendations: - 1000 ug cyanocobalamin IM - 5, 000 ug 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 - B 12 Deficiency App - For patients who have received a B 12 deficiency diagnosis. - Allows individuals to track medications and symptoms. - Bari. Apps - 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 - B 12 Deficiency Website/Forum - All-encompassing site which provides information regarding B 12 deficiency, who is at risk, symptoms, testing, treatments and more - Includes a blog and Facebook page for patients to connect with others - B 12 Awareness Website/Forum - Provides information regarding B 12 deficiency, other related disorders and various tools for press, movies, books and associated foundation - Bariatric. Pal Website/Forum - Appears useful and motivating for pre and post-bariatric surgery patients. There 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 1 x/mo -Transcobalamin -Serum homocysteine -Serum folate levels 2. Measure weight 1 x/mo. 3. Follow up with food recalls (every month until anemia is resolved) to determine if more B 12 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 - B 12 deficiency is common in gastric bypass patients d/t low IF production - Elderly have hypochlorohydria which is important for enzyme activation of proteases and B 12 absorption - To metabolize folate to its active form, vitamin B 12 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. 2 ng/d. L), and decreased serum vitamin B 12 (11. 1 ng/d. L). - Good sources of folate and B 12 Folate: lentils, pinto beans, garbanzo beans, navy beans, black beans, liver, and asparagus B 12: 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