247/248: Other Anemias (Iron/Chronic Disease, Megaloblastic) Flashcards
What are the two main causes of megaloblastic anemia?
- B12 deficiency
- B9 (folic acid) deficiency
When is it appropriate to use iron to treat anemia of inflammation?
When there is a concurrent iron deficient state
If it’s just anemia of inflammation, don’t use iron
What findings on peripheral blood smear are indicative of megaloblastic anemia? (3)
- Hypersegmented neutrophils (6+ lobes)
- Macrocytes and macro-ovalocytes
- Large, oval-shaped blood cells
- Increase in MCV
- Low blood counts overall
How can levels of homocystine and methylmalonate differentiate between folate (B9) vs. B12 deficiency?
-
Folate (B9 )deficiency
- High homocysteine
- Normal methylmalonate
-
B12 deficiency (for B12, BOTH are high)
- High homocysteine
- High methylmalonate
Both will have megaloblastic anemia; only B12 deficiency will have neurologic sx (subacute combined degeneration)
Is pure dietary deficiency more likely to cause Folate/B9 or B12 deficiency?
Folate/B9 deficiency
- B9 is found in leafy green vegetables; 3-4 months of body stores*
- B12 is found in meat, eggs, dairy; 2-4 years of body stores => deficiency likely results from malnutrition and malabsorption; look for other deficiencies*
Describe the pathogenesis of anemia of inflammation (aka anemia of chronic disease)
It all starts with inflammatory stress
- -> Increased hepcidin
- -> Ferroportin is degraded
- -> Iron cannot be absorbed from the GI tract, and it is sequestered as ferrtin
- -> Ferritin increases, but cannot be delivered to erythroid marrow (also, ferritin is an acute phase reactant)
- vs. IDA, where ferritin is reduced
- Iron is in the body, just can’t be used
What are the dietary sources of B12?
Meat, eggs, dairy
Not present in vegetables!
Body can store 2-4 years => dietary deficiency alone usually does not cause B12 deficiency0
How will the following vary in a patient with anemia due to rheumatoid arthritis?
- Iron:
- % saturation:
- Iron binding capacity (IBC or TIBC):
- Ferritin:
- Iron: Low
- % saturation: Low
- Iron binding capacity (IBC or TIBC): Normal
- Ferritin: High
Anemia of chronic disease/inflammation
- -> Increased hepcidin*
- -> Iron sequestration in storage sites (Ferritin), but cannot be used bc hepcidin is degrading ferroportin*
List 2 clinical scenarios where we would expect hepcidin to be suppressed
Iron deficiency
Hypoxia
What is the first line treatment for hemochromatosis?
Phlebotomy
Only use iron chelation if a pt has concurrent anemia (low hemoglobin), and never use with hereditary hemochromatosis
What CNS manifestation results from B12 deficiency?
Subacute combined degeneration
- Demyelination of neurons of the
- Spinal column- parathesias of the hands and feet, loss of vibratory and position sense, unsteadiness of gait
- Cerebral cortex- dementia, personality changes, distrubance in taste/smell
How will the following vary in a patient with hemochromatosis?
- Iron:
- % saturation:
- Iron binding capacity (IBC or TIBC):
- Ferritin:
- Iron: High
- % saturation: High
- Iron binding capacity (IBC or TIBC): Normal or decreased
- Ferritin: High
- Hemochromatosis = defect in hepcidin , hepcidin is reduced*
- →Ferroportin always active→absorb way too much iron*
List 2 clinical scenarios in which we would expect hepcidin to be upregulated
Iron sufficiency/overload
Inflammation (IL-6)→ anemia of inflammation/chronic disease
(Increased hepcidin→ decreased ferropotin→ decreased iron)
What is the next step in evaluating a patient who has a new iron deficiency anemia?
Rule out bleeding
Then, figure out the underlying disease process
IDA is always caused by an underlying disease or bleeding
Will the bone marrow be hypercellular or hypocellular in B12/folate deficiency?
Hypercellular
Low peripheral blood counts with hypercellular marrow => megaloblastic anemia
Describe the absorption of B12
- B12 is liberated from binding proteins by gastric acid
- B12 binds salivary haptocorrin (HC)
- B12 released from HC by pancreatec proteases
- B12 binds intrinsic factor (from gastric parietal cells)
- B12-IF complex is absorbed in the ilium
- 3-4 years of body stores; malabsorption is more likely than malnutrition*
- Malabsorption may be caused by low gastric acid, gastric bypass, deficient IF, pancreatic insufficiency, intestinal diseases*
What is pernicious anemia?
How does it affect B12?
- Auto-antibodies destroy gastric parietal cells and intrinsic factor
- -> Less HCL
- -> Less intrinsic factor
-
Results in impaired B12 absorption
- Megaloblastic anemia
- Subacute combined degeneration
