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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