Anemia Due to Decreased RBC Production Flashcards
- Describe some of the major causes for underproduction anemia and typical clinical and laboratory findings.
Conditions associated with anemia of chronic disease:
- Chronic infections or non-infectious inflammation,
- malignancies, -lead intoxication, -renal insufficiency,
- endocrine disorders
- In chronic disease (malignancy, infection, inflammation):
- TNF and IL-1 decrease iron availability, which causes decreased EPO production and decreased erythropoiesis.
- INF-beta and INF-gamma inhibit erythropoiesis as well
- All this leads to decreased RBC production
- Clinical features depend on actual disease; lab findings are anemia, normochromic/normocytic or microcytic/hypochromic.
- Decreased serum Fe, TIBC, EPO, and retic count, but increased ferritin
- Lead inhibits protoporphyrin synthesis and iron availability (?) –> degraded heme and hemoglobin.
- Can see personality changes, irritability, headache, abdominal pain, vomiting
- See anemia, decreased retic count, but increased zinc protoporphyrin and lead. Microcytosis and hypochromia.
- No kidney function = no EPO = decreased RBC production.
- Clinical features will relate to renal dysfunction (fatigue, pallor, exercise intolerance, anemia)
- Lab finding = worse anemia, normochromic/normocytic. Decreased retic and EPO
- Endocrine disorder presents as hypo- or hyper-active, weight change –> look at thyroid function.
- Nausea, vomiting, dehydration, circulatory collapse –> check adrenal function.
-Hypothyroidism = normochromic, normocytic. Hyperthyroidism = normocytic, maybe micro. Adrenal = normocytic. Each include anemia and decreased retic count.
- Describe the pathophysiology of the anemia of chronic disease.
see card one
- Describe the rationale and indications for the use of erythropoietin in the management of underproduction anemia.
-For chronic syndromes, treat underlying disease (decrease cytokines and ILs) and if permissible, treat with EPO.
- For lead intoxication, chelate.
- For renal insufficiency, administer EPO.
- For endocrine disorders, replace hormones.
- Use of transfusion and EPO in chronic diseases:
- Transfusion only when anemia is so severe, risk for cardiovascular decompensation
- Use EPO to treat anemias for which there is an absolute deficiency or decrease of cytokine out of proportion to HCT level.
- Explain the biochemical basis for B12 and folate deficiency leading to a macrocytic anemia.
- Both B12 and folate are necessary to support proliferation and maturation of all cells.
- Deficiencies have profound effects, like increasing cell size and arresting them in S phase –> cells then undergo destruction and you have ineffective erythropoiesis in marrow.
- Anemia is very prominent (sometimes neutro- and thrombocytopenia).
- This is because they are critical for synthesis of methionine from homocysteine, purine and pyrimidine biosynthesis, and production of thymodylate for DNA synthesis.
- They are critical co-factors for hematopoiesis.
- Tell the difference between the deficiencies by looking at methylmalonic acid levels ( If these levels are high = B12 deficiency).
- Identify the dietary sources of vitamin B12 and folate and describe their associated sites and mechanisms of absorption, means of transport, and duration and location of storage.
- Get B12 through meat, eggs, and milk.
- Once ingested, it is bound by intrinsic factor (IF) in stomach and takes it to the terminal ileum to be absorbed –> there it gets bound by TcII and transported to the liver for storage (or to other tissues for use).
- Deficiency of B12 normally not through diet, but via autoimmune disease, IF deficiency, malabsorption, defective transport/storage, or metabolic effect.
-Folate provided by cereals, breads, fruits and veggies, meats and fish. Also in milk. Absorbed in the jejunum and transported to tissues or liver for storage (as methyltetrahydrofolate). Folate deficiency IS due to dietary intake, malabsorption, drugs, and toxins, inborn errors in metabolism, increased demand, increased loss/metabolism.
- Describe the findings in the peripheral blood and bone marrow in a patient with B12 or folate deficiency.
- Both of these (B12 and folate) deficiencies result in megaloblastic anemia.
- Folate deficiency (particularly in malabsorption/alcoholism) happens quicker than B12 deficiency (malabsorption).
- Smear will show megaloblastic changes, increased RBC, macrocytosis/ovalocytes, and hypersegmented neutrophils.
- Can see erythroid hyperplasia, (though normally M:E ratio favors myeloid).
- Marrow precursors show large, immature nuclei.
- Macrocytosis, ovalocytes, hypersegmented nuclei, poikilocytes/fragmentation. Decreased retic count.
- Neurologic features common in B12 deficiency –>sensory losses, proprioception losses, ataxia/spasticity/gait disturbances, + Babinski test, cognitive/emotional changes. May or may not have anemia.
May see anemia, increased MCV, low retic count/index, and increased unconjugated bilirubin and LDH.
-Distinguishing tests include measuring serum cobalamin/B12 levels, folate levels, plasma homocysteine levels, succinyl CoA (B12).
Schilling test give radiolabeled cobalamin (orally) and then give unlabeled cobalamin IM. More radiolabeled in urine if being absorbed orally.
- Describe the differences between vitamin B12 deficiency and folate deficiency with respect to their most common causes, time to development, presence of neurologic abnormalities, and laboratory studies used to make a diagnosis.
see 6
- Describe the appropriate therapies for B12 deficiency and folate deficiency.
If cobalamin deficiency, 1 mg injections weekly, then monthly. If malabsorption isn’t an issue, 2 micrograms orally bid.
Folate can be given 1mg/day orally and parenterally.
Anemia will reverse rather quickly.
