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Hematology Lecture 13: LMU
Anemias Caused by Defects in DNA Metabolism: Macrocytic-Normochromic Anemias (Megaloblastic Anemia)
Terms in this set (30)
HgB: Males 16+/-2g/dL Females 14+/-2g/dL
MCV (Hct/RBC)(10) in fL:
MCHC (HgB/HCT)(100) in g/dL:
What causes a Megaloblastic anemia?
Defective DNA synthesis (nuclear maturation problems)
Clinical Manifestations of Megaloblastic Anemia:
-RNA synthesis continues, resulting in an increase in cytoplasmic mass and macrocytic anemai
-Thus, in megaloblastic anemia, nuclear maturation lags behind cytoplasm maturation
Causes of Folate Deficiency:
*Increased need (Pregnancy,Infants,Children)
*Impaired absorption in the GI
Causes of Vitamin B12 Deficiencies:
*Lack of haptocorrin and/or intrinsic factor:
-Vitamin B12 is bound by the saliva protein haptocorrin
-Trypsin releases B12 from haptocorrin in the stomach
Intrinsic factor binds B12 and transports it across the cell membrane
*Fish tapeworm(Diphyllobothrium latum)
What is asynchronism?
-State in which nuclear maturation and the cytoplasmic maturation takes place at different rates
-This is an important characteristic of the megaloblastic anemais
What is "Megaloblastic madness?"
-Pronounced Neurological Symptoms:
*Root Cause: Demyelinization of the spinal cord and peripheral nerves
*Numbness, and tingling in toes and fingers
*Loss of balance
*Impairment of walking
These patients may be falsely diagnosed as having had a stroke
Megaloblastic anemias are often referred to as the ________ anemias.
The term megaloblastic refers to a specific _____________________________.
morphologic changes in developing RBCs
Vitamin B12 & Folic Acid
-Under normal conditions, the B12 stores in the liver is sufficient to sustain the needs of the body for 3-5 years; Depletion is slow
-Folic acid is not stored as well as B12, so depletion of folic acid occurs is more rapidly than vitamin B12
Folic acid deficiency is more common than a B12 deficiency
Macro-Normo Anemias: Vitamin B12 Deficiencies
Pernicious Anemia (PA): MOST COMMON
Macro-Normo Anemias: Folic Acid Deficiencies
-Chemotherapy for Cancer
Macro-Normo Anemias: Vitamin B12 & Folic Acid Deficiency
Problem: Malabsorption of VitB12 due to lack of intrinsic factor
-Parietal cells of the gastric mucosa secrete both HCL and intrinsic factor, which is necessary fro VitB12 absorption across the intestinal mucosa in the ileum
-Without intrinsic factor, VitB12 can't be absorbed and utilized by the body
-PA patients often produce antibodies against intrinsic factor and autoantibodies to the parietal cells of the stomach
PA is an autoimmune disorder in which antibodies are produced against either intrinsic factor or the parietal cells that produce intrinsic factor.
The lack of intrinsic factor that results in an inability to absorb Vitamin B12
Classic Symptoms of PA
-Yellow skin pallor
-Pale nail beds and eyelids
*Abdominal pain, nausea, diarrhea
*"megaloblastic madness": loss of memory, disorientation
*Loss of balance, numbness, tingling if arms and legs
May appear as if the patient has had a stroke
CBC Results in PA:
*Low WBC, RBC, H/H, Plt
*High MCV (indicates macrocytosis; usually 100-150 fL)
*MCHC is usually normal
Macrocytic normochromic anemia
Differential Results in PA:
---Be Conservative: Even healthy people may have an occasional 5 lobed segmented neutrophil.
Other Test Results in PA:
*Low Retic Count (even in the presence of anemia)
*Impaired DNA synthesis
--Low Vitamin B12
*Normal folic acid (folate)
*High LDH (lactate dehydrogenase)
--Caused by the breakdown of RBC precursors
Hypersegmented Neutophil in PA
Bone Marrow Findings in PA:
-Megaloblastic Erythroid Hyperplasia
*Characteristic of PA
*All NRBC are larger than normal.
*Defective immature RBCs (defective DNA synthesis) die before leaving the marrow.
*Even the neutrophils are larger than normal.
*Low M:E ratio due to erythroid hyperplasia
--Normal: 3:1 - 4:1
Giant Metamyelocytes in Megaloblastic Anemia:
Schilling Test for PA:
-Distinguishes PA from other B12 deficiencies.
-Remember: PA is caused by a lack of Intrinsic Factor
Principle: Phase I:Screening
-Patient is given an oral dose of radioactive B12.
-Several hours later a nonlabeled "flushing dose" of vitamin B12 is given IM so that the liver will be saturated and the labeled B12 will be free to be excreted into the urine.
-If the patient can absorb the labeled B12 into the blood stream (i.e., has normal intrinsic factor level), some labeled B12 will be excreted into the urine.
-Patient with PA can't absorb the radioactive B12 effectively, so the urine excretion will be less than 7% of the dosage given. (The radioactive B12 will pass into the stool.)
Schilling Test for PA:
Principle: Phase II: Confirmation
-A dose of radioactive B12 is given to the patient, along with intrinsic factor.
-If radioactive B12 appears in the urine, dose of intrinsic factor corrected the intrinsic factor deficiency: PA is confirmed. (The Schilling Test corrects to normal with the addition of intrinsic factor)
-If radioactive B12 does not appear in the urine (but rather is passed into the stool), other causes of malabsorption, other than intrinsic factor deficiency, must be investigated; PA is not confirmed.
PA & Achlorhydria
-Sometimes PA patients demonstrates achlorhydria.
*Achlorhydria: Lack of free HCL in the stomach secretions, even after histamine stimulation
*Reason: Progressive loss of parietal cells with their secretory products, H+ and intrinsic factor.
*N/G (naso-gastric) tube is inserted into the stomach to remove and titrate stomach HCL.
*Patient is given an injection of histamine, which should stimulate gastric HCL production.
*PA patient: No significant increase in HCL secretion (Some PA patients lack stomach acid).
Treatment of PA
-Monthly injections of Vitamin B12 for life
**Question: Why must the Vitamin B12 be injected instead of oral administration?
-The Body's Response to Treatment
*Prompt and brisk
*BM morphology will begin to revert to a normoblastic appearance within a few hours of treatment
*Substantial reticulocyte response is apparent in about 1 week
*HgB levels will rise in about 3 weeks
Other B12 Deficiencies (Beside PA)
*Part of the stomach is removed
*Intrinsic factor secreting cells are gone
*Oral vitamin B12 can't be absorbed
*Intestinal enteritis, with chronic diarrhea, affects the ileum where B12 is absorbed.
*This fish tapeworm loges in the ileum and splits vitamin B12 from intrinsic factor, rending the vitamin unavailable for host absorption.
B12 Deficiency vs Folate Deficiency
-Same PB and BM findings
-Same PB and BM findings
*Sprue: Intestines can't absorb food properly
*Nontropical sprue: Intolerance of gluten in the diet; remedy is to eliminate wheat products from the diet.
-Associated with chronic diarrhea
*The macrocytic anemia in these cases is caused by a lack of folic acid in the beginning and a lack of B12 as the disease becomes chronic.
(Remember that the liver stores 3-5 years worth of B12).
When you see a macro-normo anemia results on a CBC, think B12 or folic acid (folate) deficiency
-Liver disease can cause a macrocytic anemia but with no megaloblastic appearance in the bone marrow or peripheral blood
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