Nutritional Anemias Flashcards
Whats another name for macrocytic?
Megaloblastic
What do the lack of B12 and folate cause?
4
- effect the development of RBCs in the bone marrow
- slows the synthesis of DNA but not RNA
- The RBC increases in size before dividing resulting in macrocytic RBCs
- The mechanism of development of the hypersegmented neutrophils is not well understood
What are the only dietary source of B12 for humans?
Meat & dairy products
What does adequate B12 absorption cause?
5
- Dietary intake
- Acid-pepsin in the stomach to liberate Cbl from binding to proteins
- Pancreatic proteases to free Cbl from binding to R factor (R factor delivers it to the duodenum)
- Secretion of intrinsic factor (IF) by the gastric parietal cells to bind Cbl
- An intact ileum with functional Cbl-IF receptors
- Dietary intake
- Acid pepsin in the stomach (binds B12 to proteins)
- Pancreatic proteases (binds B12 to R factor)
- gastric parietal cells (binds B12 to IF)
- Funtional Ilieum with Cbl-IF receptors
How is pernicous anemia caused?
2
Autoimmune attack on gastric IF
- One type of anti-IF antibodies blocks the attachment of Cbl to IF
- Other type blocks attachment of the Cbl-IF complex to ileal receptors
Who is pernicuous anemia usually seen in?
2
Usually seen in older adults
Seen primary in African Americans & Caucasians/not Hispanics and Asians
What does chronic atrophic gastritis lead to? 2
Whats the pathology behind the above answer?
Leads to a decline in IF production, less acidic pH in the stomach
Associated w/ autoantibodies directed against gastric parietal cells
What kind of cancer is cancer is chronic atrophic gastritis associated with?
2
gastric cancer and gastric carcinoid tumor
Factors that can contribute to food cobalamin malabsorption?
12
- Gastrectomy*/gastritis—absence of gastric acid & pepsin results in impaired liberation of Cbl from its binding to food proteins along w/ the absence of IF
- Gastric atrophy/achlorhydria
- Heilobacter pylori infection (link suggested)
- Intestinal bacterial overgrowth secondary to antibiotic treatment
- Long-term ingestion of metformin, antacids, H2 receptor antagonists & PPI
- Chronic alcoholism**
- Gastric surgery/reconstruction for obesity (bariatric surgery)
- Pancreatic exocrine factors
- Inadequate dietary intake (strict vegans, pregnant women who limit their animal protein intake)
- HIV infection (poor nutrition, chronic diarrhea, ileal dysfunction and exudative enteropathy)
- Crohn’s disease
- Fish tapeworm ingestion
Lab presentation of macrocytic anemia?
1. MCV > 100 fL Often— 2. elevated iron levels, 3. indirect bilirubin & LDH: 4. Peripheral smear—megaoblasts, hypersegmented neutrophils & macrocytosis
What do elevated indirect bilirubin and LDH levels suggest?
2
indicating increased RBC breakdown due to both peripheral destruction & ineffective erythropoiesis
If the macrocytic anemia is severe enough what things could occur?
2
thrombocytopenia & neutropenia
How do B12 and folate levels cause hyperhomcysteinemia and what is this a risk factor (2) for?
- Both Cbl & folate required for the metabolism of homocysteine to methionine
- Elevated homocysteine levels are a risk factor for atherosclerosis and venous thromboembolism
What neurological changes are seen in B12 deficiency?
3
- Peripheral neuropathy (numbness and tingling in the hands and feet)
- Progress to severe weakness, spasticity, clonus and even incontinance.
- Memory loss, irritability and dementia
What are these neurological symtpoms due to?
Due to a defect in myelin formation of unknown mechanism
What causes an increased risk of osteoporosis in pts with B12 and folate deficiencies?
Due to suppression of osteoblast (laying down of bone) activity
Increased risk of hip & spine fractures
Etiologies of folate deficiency?
6
poor nutrition alcoholism Infants who are mostly fed goats milk pregnancy patients with chronic hemolytic anemia drugs that interfere with it
What foods is folate found in?
4
meats, green leafy vegetables, nuts and fruit
What are drugs that interfere with folate metabolism?
3
Trimethoprim, methotrexate, phenytoin
What can folate defiency present as?
2
- Macrocytic anemia and
2. hyperhomocysteinemia
How quickly does folate deficiency occur?
4-5 months
How quickly does B12 deficiency occur?
Where are our B12 stores at?
takes years
liver
How do we replace B12?
Have to inject it IM
What are the three things that can cause macrocytic anemia?
myelodisplastic disorders, B12, folate deficiency
What would lead us to suspect B12/Folate deficiency?
4
- Presence of hypersegmented neutrophils/patient who has neurologic symptoms even if NOT anemic
- Oval macrocytic RBCs on peripheral smear
- Pancytopenia of uncertain cause
- Unexplained neurologic signs: dementia, sensory ataxia, and paresthesia’s
In what populations are you more likely to suspect macrocytic anemia?
5
- Older adults
- Alcoholics
- Patients w/ malnutrition
- Strict vegans
- Patients who have undergone bariatric surgery and are not being compliant w/ their vitamins
What would we order in a laboratory evaluation?
3
Serum B12
Serum folate
Metabolite testing
What is considered a low Serum B12?
What is considered a low folate level?
Why would we order a metabolite test?
What are we looking for with this?
3
for those w/ borderline vitamin values:
- Measure the metabolic intermediates: methymalonic acid and homocysteine
- If these are ELEVATED then true B12 deficiency exists
- If MMA is normal and homocysteine is increased folate deficiency is present
How do we diagnose pernicious anemia?
2
- Measure antibodies to IF—specificity of 100%
2. Elevated gastrin/low pepsinogen—highly sensitive if antibodies negative
How would we treat folate deficiency?
Folic acid 1-5 mg po daily for 1-4 months or until complete hematologic recovery
(usually 1mg is good)
NEED TO RULE OUT B12 DEF BEFORE YOU START TREATING FOR FOLAT DEF
How do we treat B12 def?
Usually treated w/ IM or deep SQ injections of Cbl
1000 mcg every day for 1 week
1 mg every week for 4 weeks
If the underlying disorder persists—1 mg every month
Can have sublingual
What should fall rapidly within 1 to 2 days of parenteral B12?
3
serum iron, indirect bilirubin and LDH
How will parenteral B12 affect the bone marrow?
Bone marrow changes from megaloblastic to normoblastic also
What is common during the early response in B12 treatment and what is this due to?
Hypokalemia is common during this early response due to the marked increase in K+ utilization in the production of new hematopoetic cells (using up all the K+ to make new cells)
What is absolute iron deficiency defined as?
2
- Iron stores in the bone marrow & in the liver/spleen are ABSENT
- Serum ferritin is LOW
Etiologies of iron deficiency anemia?
5
Poor dietary intake (foods, meds, celiac dz, atrophic gastritis)
Reduced iron absorption (gastric bypass)
Increased blood loss—Western world safest to assume cause is blood loss and search for that cause
Overt blood loss—obvious, surgery, menometrorrhagia, pregnancy
Occult bleeding—assume GI cancer until proven otherwise!
Intravascular hemolysis
Congenital iron deficiency
What do we assume in occult blood loss?
GI cancer until proven otherwise
What kind of anemia is characterized by Hepcidin-induced block in the release of iron from the macrophage back into circulation?
What kind of patients is this seen in?
Anemia of inflammation/ Anemia of chronic disease
Seen in patients w/ infection, inflammation, or malignancy
How do we treat anemia of chronic disease?
Treatment w/ erythropoiesis-stimulating agents:
Clinical manifestations of iron deficiency anemia?
10
Asymptomatic** Weakness Fatigue Headache Irritability Exercise intolerance Glossal pain & reduced salivary flow May lead to exacerbation of co-morbidity (?) Pica/Paraphagia** (craving ice) Restless leg syndrome (!)
Normal serum iron levels?
Serum Iron (Fe): 60 – 170 microgm/dL
Normal ferritin levels?
females and males
Ferritin: 12 – 150 ng/mL (females):
12 – 300 ng/mL (males)
Normal Transferrin/Total iron binding capacity (TIBC) levels?
240 – 360* microgm/dL
Normal Transferrin saturation (Fe/TIBC)?
15– 50%
What our differential diagnosis for iron deficiency anemia?
3
- thalassemia
- Anemia of chronic disease
- Sideroblastic anemia (drug induced or myelodysplastic disorder)
What would be abnormal in thalassemia for labs?
3
Serum Fe are normal to high
Hgb A2 level increased
RBC count is high
What would be abnormal is anemia of chronic disease?
3
Serum Fe and TIBC are low
Normal or increased Ferritin
Whats the difference in a stain with thalassemia and a stain with iron deficiency anemia?
Both have microcytic cells but there are many many more in thalassemia
In IDA, there are few and they are pale
What is front line therapy for iron deficiency anemia?
oral iron therapy
What conditions can lead to ineffective or poorly tolerated iron therapy?
6
- GI side effects are VERY common and can lead to poor compliance
- Malabsorptive states (celiac dz, Whipple’s dz, bacterial overgrowth syndromes)
- Treatment w/ oral iron can take 6-8 wks to resolve the anemia and up to 6 months to replete iron stores
- In patients w/ inflammatory bowel dz, the use of oral iron can worsen the underlying disease
- In conditions such as heavy uterine bleeding, gastric bypass, or other causes of heavy blood loss oral iron may be unable to keep up w/ blood loss
- Dialysis patients are unable to utilize orally administered iron
Where is iron absorbed?
In the blood
What should iron salts not be given with?
4
- Food because many substance in food bind iron and impair its absorption
- Antacids, H2 blockers, PPIs
- Calcium containing foods, cereals, dietary fiber, coffee, tea and milk
- Certain anitbiotics (e.g. quinalones, tetracyclines)
When should iron be given if taking antacids?
Iron should be given 2 hours before or 4 hours after antacids
What is the recommended treatment for IDA?
150 – 200 mg of ELEMENTAL Fe daily
What Gi effects do 50% of pts experience?
6
nausea, constipation, diarrhea, epigastric pain, vomiting, black stools
What are our treatment options if the GI side effects from taking iron are too much for the pt?
5
- Switch to a preparation w/ lower dose of elemental iron
- Slowly increase from 1 pill a day to 3
- Iron may be taken with meals, but it will decrease absorption some (stay away from calcium)
- Use a liquid preparation (especially helpful in older adults)
- Try IV iron
IV IRON PREPARATIONS SIDE EFFECTS
Systemic SE—fever, arthralgias, myalgias
Flare of arthritis in patients w/ inflammatory arthritis commonly occurs
This can usually be prevented by premedication w/ IV methylprednisone before infusion
4 days of prednisone orally after infusion