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75 Cards in this Set
- Front
- Back
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What is a macrocytic anemia?
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It is a morphologic classification of anemia having mean corpuscular volume (MCV) greater than 100fL, elevated mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin content (MCHC) within normal range.
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What are the two categories of macrocytic anemia?
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Megaloblastic and nonmegaloblastic processes
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What are macrocytic anemias termed as?
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Macrocytic and normochromic
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What anemia has a vitamin b12 or folic acid deficiency? also known as a pernicious anemia.
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Megaloblastic
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What anemia is unrelated to a nutritional deficiency?
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Macrocytic but not megaloblastic
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What does vitamin B 12 or folic acid deficiency lead to?
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It leads to impaired DNA synthesis, a serious condition, and affects all readily dividing cells, skin cells, hematopoietic cells, and epithelial cells.
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What is a tropical sprue most common in?
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It is common in malabsorption syndromes contributing to acid deficiency.
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What does a tropical sprue effect and what does it result from?
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It affects overall digestion and is thought to result from infection, overgrowth of bacteria, or poor nutrition.
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What is necessary for b12 to be absorbed?
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Intrinsic factor
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What does the morphology of megaloblastic anemia look like?
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The megaloblastic red blood cell precursors are larger, the nuclear structure is less condensed, and the cytoplasm is very basophilic (much bluer).
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Is there asynchrony between the age of the nuclear material and the age of the cytoplasm?
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Yes
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what are the 2 functions that normal red blood cell series programmed for?
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Hemoglobin synthesis and nuclear explusion.
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What do the megaloblastic chromatin in the megaloblastic pronormoblast and megaloblastic basophilic normoblast look like?
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open-weaved
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What is wrong with the open weave look of the megaloblastic chromatib?
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It is fragile and lacks a composition and condensation of the nucleus ready to be delivered from the cell.
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What does the cytoplasmic material look like from the early megaloblastic precursors?
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Extremely basophilic, much bluer than normal precursors.
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What can help differentiate oneself from another?
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Nucleus to cytoplasm ratio, cell size, nuclear material, and cytoplasm color in each stage.
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is the bone marrow hypercellular in megaloblastic conditions?
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Yes
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Are the white blood cell precursor cells large, especially the metamyelocytes?
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Yes
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What is the myeloid to erythroid ratio in megaloblastic anemia and what is it reflecting?
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1:1 or 1:3 and reflecting erythroid hyperplasia that you would see in the bone marrow responding to anemia.
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what hemolyzes before its maturation cycle is complete?
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Megaloblastic precursor cells, especially at the polychromatophillic and basophilic states.
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What would happen if erythropoiesis was effective and the bone marrow was responding to anemic stress?
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The peripheral smear would show evidence of the regenerative marrow process.
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What key structure does DNA synthesis depend on?
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thymidine triphosphate (TTP)
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thymidine triphosphate cannot be formed unless it receives what?
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Unless it receives a methyl group from methyl tetrahydrofolate or folic acid.
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what is the cofactor responsible for transferring the methyl group to methyl tetrahydrofolate?
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Vitamin b12
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Vitamin b12 and folic acid are the key to the formation of what?
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TTP
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If TTP cannot be synthesized, what is it replaced by?
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Deoxyurindine triphosphate (DTP)
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What does the synthesis of DTP lead to?
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It leads to nuclear fragmentation and destruction of cells and impaired cell division.
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What are the main producers of vitamin b12, a group of vitamins known as cobalamins?
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Microorganisms and fungi
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What is the recommended daily allowance of vitamin b12?
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2.0 micrograms
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How much vitamin b12 is stored in the liver?
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1 to 2 milligrams
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Does dietary requirements increase during pregnancy and lactation of vitamin b12?
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Yes
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How long does it take vitamin b12 stores to develop and why?
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It takes years to develop because the storage rate is so high
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What is the minimum daily requirement of folic acid?
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200 micrograms
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How much folic acid is stored in the liver?
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5 to 10 milligrams is stored in the liver
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Why does folic acid deplete so quickly within months?
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Because the daily requirement is so much higher
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Why are pregnant women in courage to increase their folic acid intake?
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Because decreased folate may lead to neural tube defects.
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What is the process of b12 being incorporated into bone marrow and other tissues?
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Initially, the vitamin is taken in from the diet and separated from food by salivary enzymes.
Next, vitamin b12 is transported to the stomach, where it combines with intrinsic factor, a substance secreted by the parietal cells of the stomach. Intrinsic factor and vitamin b12 form a complex that precedes to the ileum. Vitamin b12 is absorbed through the brush borders of the ilium, and intrinsic factor is degraded. When the vitamin b12, it is carried into the plasma and forms a complex with tdanscobalamin 2 (TC2), which transports it to the circulation. From the circulation vitamin b12 is transferred to the liver, the bone marrow, and other tissues. |
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What is the movement of folic acid into the circulation and tissues?
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When folic acid is ingested and absorbed through the small intestine, it is reduced to methyl tetrahydrofolate through dihydrofolate reductase, an enzyme available in mucosal cells.
The reduced form is delivered to the tissues. When inside the tissues, the methyl group is released to combine with homocysteine, an early precursor to DNA synthesis. homocysteine is converted to methionine, an amino acid. |
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What happens if folate or vitamin b12 metabolism is flawed?
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homocysteine accumulates, potentially leading to thrombosis. Which leads to a consequence in the hematostatic system.
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what symptoms are accompanied by severe anemia?
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Hgb decreased from 7 to 8g/DL
shortness of breath light-headedness extreme weakness pallor patients may also experience glossitis, dyspepsia, or diarrhea |
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patients with numbness, vibratory loss (paresthesias), and difficulties in balance and walking experience what?
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neurologic involvement
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what does vitamin b12 deficiency cause?
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demyelinization of the peripheral nerves, the spinal column, and the brain, which can cause many more sever neurologic symptoms, such as spasticity or paranoia.
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patients with jaundice have megaloblastic anemia RBC lifespan of how many days?
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75 days
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what does the CBC show of megaloblastic anemias?
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pancytopenia (low WBC, low RBC, and low platelet count), platelet count may be only borderline low.
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what should raise the suspicion towards a megaloblastic process?
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pancytopenia in the CBC combined with macrocytosis because few other conditions show this pattern. (I.e., aplastic anemia, hypersplenism)
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what inclusion is formed from megaloblastic erythropoiesis?
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howell-jolly bodies, they are larger and more fragmented than normal.
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what are other features of a megaloblastic anemia?
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low reticulocyte count (<1%), RDW is increased, owing to schistocytes, target cells, and teardrop cells.
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what does the peripheral smear of megaloblastic anemia show?
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macrocytes, macro-ovalcytes, hypersegmented multi-lobed neutrophils, and little polychromasia with respect to the anemia.
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what is the major marker for megaloblastic anemia in a peripheral smear?
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presence of hypersegmented neutrophils
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pernicious anemia
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when problems with intrinsic factor develop, a condition called pernicious anemia.
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how many antibodies to IF are present in patients with pernicious anemia?
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56% of patients with pernicious anemia, 90% of patients showing parietal cell antibodies, suggesting a strong autoimmune component to this disorder.
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pernicious anemia occurs more in patients with what other diseases?
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diabetes
thyroid conditions autoimmune processes |
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what may also contribute to severe food malabsorption?
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helicobacter pylori infections and long-term use of antacids.
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what is blind loop syndrome?
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overgrowth of bacteria in a small pocket of malformed intestine.
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what may compete for vitamin b12 when it attaches to the intestine and what do individuals exhibit if they have this parasite?
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fish tapeworm diphyllobothrium latum
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what is the most common vitamin deficiency in the US?
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folic acid deficiency
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what happens to the villi in a patient with tropical sprue?
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flattened, leading to poor absorption
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what are symptoms or tropical sprue?
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diarrhea
indigestion weight loss |
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folic acid deficiency may be expected in individuals taking what medication?
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methotrexate or other chemotherapy drugs that directly affect DNA synthesis of normal and abnormal dividing cells.
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what are common features of megaloblastic anemias?
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pancytopenia
increased MCV hypersegmented neutrophils increased bilirubin increased LDH hyperplasia in the bone marrow decreased M:E ratio reticulocytopenia |
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what are serum levels of bit. b12 determine by?
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radioimmunoassay
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what value indicates that addition testing may need to be done for serum vit b12?
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<200ng/L
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what is elevated when vit. b12 is deficient?
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metabolites methylmalonic acid (MMA) and hemocysteine
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what can MMA and homocysteine differentiate?
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vit b12 from folate acid
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what evaluations are cost effective, reliable, and highly specific for a diagnosis of pernicious anemia?
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intrinsic factor antibody evaluations
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what are the 2 classifications of intrinsic antibody?
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blocking antibody and binding antibody.
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blocking antibodies
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inhibit the binding of vit b12 to intrinsic factor
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binding antibodies
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prevent the attachment of intrinsic factor-vitamin b12 complex to receptors in the small intestine.
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what kind of texting can delineate the nature of IF antibody?
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radioimmunoassay
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what is important to observe carefully in the peripheral smear when macrocytes appear?
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shape
color hypochromia (this determines if the macrocytosis is megaloblastic or nonmegaloblastic) |
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what are megaloblastic macrocytes?
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large and oval, with a thicker exterior membrane and lacking hypochromia.
(indicator of nonmegaloblastic origins) |
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what other conditions may macrocytosis be seen?
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hypothyroidism
chronic liver disease alcoholism chemo treatment myeloysplastic disorder |
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what are oval macrocytes seen in?
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folic acid deficiency
vit b12 deficiency pernicious anemia |
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what are round hypochromic macrocytes seen in?
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alcoholism
hypothyroidism liver disease |
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what are blue-tinged macrocytes seen in?
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neonate response to anemic stress
response to anemic stress |
