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30 Cards in this Set
- Front
- Back
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Blood and Lymph- Macrocytic Anemia Anemia by Turnicky
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Blood and Lymph- Macrocytic Anemia Anemia by Turnicky
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Macrocytosis. what does the MCV say? What are the two broad categories?
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-MCV >100 fl
-Increased MCV may be due to many reasons, review pt. History and blood smear Two broad categories: -Round macrocytosis (non-megaloblastic) -Oval macrocytosis (megaloblastic) |
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Megaloblastic Macrocytic Anemia
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Inherited: rare
Acquired: -B12/Folate deficiency -Chemotherapeutic or retroviral agents -Myelodysplastic syndromes -Drugs associated with impaired absorption of B12/fotate (contraceptives, anticonvulsants) -Toxins (benzene, arsenic) |
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Round Macrocytosis , Non-Megaloblastic.. mostly seen where?
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-Alcoholism
-Liver disease Rarely: -Renal disease/Hypothyroidism (myxedema of the red cell) -Usually Normocytic -Patients may develop enteropathy with poor absorption of B12/folate |
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Why do you have an oval macrocytosis, (megaloblastic)?
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A DNA replication problem. RNA continues to be translated and transcribed with resulting growth of the cytoplasm while nucleus lags behind. One or more cell divisions are skipped leading to larger than normal cells.
something immature is larger, bigger, stains more deeply. |
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Oval Macrocytosis Megaloblastic causes
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-Drug effect including chemotherapy, antiretroviral. (common cause of increased MCV)
-Folate/B12 deficiency (see hypersegmented PMNs) -Myelodysplasia (PMNs often hyposegmented) |
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Spurious (falsely) Increased MCV
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Autoantibody production, hyperglobulinemia or cold agglutinins. RBC clumping and sticking together as they pass the instrument detector
-Rouleaux formation gives a false reading that the cells are very large, when actually it's just a clumping of cells that gets detected as one cell. -Patients with increased reticulocyte counts can also have an increased MCV due to the larger size of the reticulocyte -Extreme Leukocytosis (Chronic Lymphocytic Leukemia) Automated counters score wbcs as rbcs |
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S& S of anemia
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S& S of anemia: lethargy, weakness, pallor.
-Atrophy of mucosal surfaces, tongue, GI, vaginal (impaired DNA synthesis of proliferating cells) may lead to malabsorption. -Consider in all infants with failure to thrive |
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If there is a B12 deficiency, what type of neurologic disturbances may you see?
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-Damage may occur before anemia
-Parethesias reflect peripheral neuropathy -Proprioceptive disturbance of legs may cause abnormal gait. -Neuropsychiatric disorders *neurologic symptoms precede hematologic findings especially in infants! |
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Megaloblastic Anemia: Lab
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-Macrocytic normochromic
-MCV> 100 fl -MCH often increased due to large cell volume, but MCHC is normal -RDW elevated (anisocytosis) -Very low reticulocyte count -May see normal MCV if concurrent iron deficiency |
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What is the triad that you see in megaloblastic anemia?
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-oval macrocytes,
-Howell-jolly bodies and -hypersegmented neutrophils unlike other anemias.. all 3 cell lines are involved. neutrophils tend to be left shifted and larger than normal. you may see pancytopenia (diminished RBC, WBC, platelets) |
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What is the active form of folate? What is it vital for?
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-Tetrahydrofolate is the active form of folate
-THF is vital in the metabolism of nucleotides and amino acids. -Folic acid deficiency causes a block in the conversion of dUMP to dTMP resulting in defective DNA synthesis. folate deficiency frequently from inadequate dietary intake (increased requirement in pregnancy and hemolytic anemia), malabsorption in small intestinge, and drugs (oral contraception, long term anticoagulants, phenobarbitol) |
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What is the first morphologic observation for folic acid deficiency?
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hypersegmented neutrophils (11 wks).
anemia appears last (20 weeks) see hypersegmented neutrophils, think b12/folate deficiency. |
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What do you need Cobalamin B12 for?
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-Necessary for synthesis of methionine, the central reaction in DNA synthesis
-Deficient B12 means folate trapped in the n-methyl THF form, meaning B12 deficiency leads to functional folate deficiency. |
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Does the body have a lot of B-12?
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B12 Non-dietary Deficiency:
-In contrast to folate, the body has copious amounts of stored B12 (2-6years) -Deficiency due to dietary intake is uncommon unless a strict vegetarian. Abnormal gastric environment: Achlorhydria; Partial gastrectomy -Deficient Intrinsic factor, due to destruction of parietal cells by auto-antibodies (pernicious anemia) -Malabsorption syndromes, pancreatic insufficiency, surgical removal of the ileum. |
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How is B-12 absorbed
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-Stomach: B12 binds with R-binding proteins
-Duodenum: pancreatic protease digestion of R-binding proteins, releasing B12, rapidly bound to IF (from parietal cell), binds to specific IF receptors of the terminal ileum. |
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What is the most common cause of B12 deficiency?
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Pernicious Anemia:
-Specific term to define the megaloblastic anemia due to absence of IF secondary to gastric atrophy. -Frequently occurs with other autoimmune diseases (Graves, Hashimoto’s) -Auto-antibodies directed against parietal cell Auto antibodies to IF; are of two types: -Blocking antibody preventing formation of IF-B12 complexes -Binding antibody react with IF-B12 binding site preventing absorption in the ileum. |
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Gold Standard test for pernicious anemia?
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Schilling Test:
-Complex -Difficult with 24hr urine -No longer front line test, but indicated in select patients -Definitive test to distinguish between B12 malabsorption, dietary deficiency or absence of IF. -B12* orally, 2hrs later unlabeled B12 IM (to saturate all B12 receptors in tissue and plasma) -Any of the oral dose absorbed in the gut and passing into the blood will be in excess of available receptors. |
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Macrocytic Anemia without Megaloblastosis . What it look like?
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-Round rather than oval macrocytes
-Hypersegmented PMNs not present -Absence of glossitis and neuropathy |
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Macrocytic Anemia with Megaloblastosis Drugs...alcohol...
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Drugs:
-Metabolic inhibitors. All rapidly proliferating cells affected, including hematopoietic cells -Chemotherapeutic: Cytosine arabinoside, Hydroxyurea, Methotrexate (a folic acid inhibitor) -Antiretrovirals Alcoholism -Multifactorial: -Dietary deficiency of folic acid -Reticulocytosis associated with GI bleeding -Associated liver disease -Toxic effect of alcohol on erythropoiesis. |
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What is the triad that you see in megaloblastic anemia?
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-oval macrocytes,
-Howell-jolly bodies and -hypersegmented neutrophils unlike other anemias.. all 3 cell lines are involved. neutrophils tend to be left shifted and larger than normal. you may see pancytopenia (diminished RBC, WBC, platelets) |
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What is the active form of folate? What is it vital for?
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-Tetrahydrofolate is the active form of folate
-THF is vital in the metabolism of nucleotides and amino acids. -Folic acid deficiency causes a block in the conversion of dUMP to dTMP resulting in defective DNA synthesis. folate deficiency frequently from inadequate dietary intake (increased requirement in pregnancy and hemolytic anemia), malabsorption in small intestinge, and drugs (oral contraception, long term anticoagulants, phenobarbitol) |
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What is the first morphologic observation for folic acid deficiency?
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hypersegmented neutrophils (11 wks).
anemia appears last (20 weeks) see hypersegmented neutrophils, think b12/folate deficiency. |
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What do you need Cobalamin B12 for?
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-Necessary for synthesis of methionine, the central reaction in DNA synthesis
-Deficient B12 means folate trapped in the n-methyl THF form, meaning B12 deficiency leads to functional folate deficiency. |
|
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Does the body have a lot of B-12?
|
B12 Non-dietary Deficiency:
-In contrast to folate, the body has copious amounts of stored B12 (2-6years) -Deficiency due to dietary intake is uncommon unless a strict vegetarian. Abnormal gastric environment: Achlorhydria; Partial gastrectomy -Deficient Intrinsic factor, due to destruction of parietal cells by auto-antibodies (pernicious anemia) -Malabsorption syndromes, pancreatic insufficiency, surgical removal of the ileum. |
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How is B-12 absorbed
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-Stomach: B12 binds with R-binding proteins
-Duodenum: pancreatic protease digestion of R-binding proteins, releasing B12, rapidly bound to IF (from parietal cell), binds to specific IF receptors of the terminal ileum. |
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What is the most common cause of B12 deficiency?
|
Pernicious Anemia:
-Specific term to define the megaloblastic anemia due to absence of IF secondary to gastric atrophy. -Frequently occurs with other autoimmune diseases (Graves, Hashimoto’s) -Auto-antibodies directed against parietal cell Auto antibodies to IF; are of two types: -Blocking antibody preventing formation of IF-B12 complexes -Binding antibody react with IF-B12 binding site preventing absorption in the ileum. |
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Gold Standard test for pernicious anemia?
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Schilling Test:
-Complex -Difficult with 24hr urine -No longer front line test, but indicated in select patients -Definitive test to distinguish between B12 malabsorption, dietary deficiency or absence of IF. -B12* orally, 2hrs later unlabeled B12 IM (to saturate all B12 receptors in tissue and plasma) -Any of the oral dose absorbed in the gut and passing into the blood will be in excess of available receptors. |
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Macrocytic Anemia without Megaloblastosis . What it look like?
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-Round rather than oval macrocytes
-Hypersegmented PMNs not present -Absence of glossitis and neuropathy |
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Macrocytic Anemia with Megaloblastosis Drugs...alcohol...
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Drugs:
-Metabolic inhibitors. All rapidly proliferating cells affected, including hematopoietic cells -Chemotherapeutic: Cytosine arabinoside, Hydroxyurea, Methotrexate (a folic acid inhibitor) -Antiretrovirals Alcoholism -Multifactorial: -Dietary deficiency of folic acid -Reticulocytosis associated with GI bleeding -Associated liver disease -Toxic effect of alcohol on erythropoiesis. |
