Module 6 Megaloblastic and non megaloblastic anemia Flashcards
b12 and folate deficiency type
megaloblastic
chronic liver disease, alcoholism, endocrine disorders
macrocytic normoblastic
proliferation defects
aplastic anemia, pure red cell anemia, Anemia chronic renal disease.
folate deficiency causes and related syndromes
nutritional deficiency increased requirement, malabsorption drug innhibition
b12 deficiency
pernicious anemia, small bowell resection, gastrectomy, malabsorption, nutritional deficiency,
normoblastic macrocytic anemia causes
alcohol, liver disease, hypothyroidism, aplatic anemia. Can be artifactual caused by cold aglutinins, hyperglycemia.
IF
required for b12 absorption. Hampered in pernicious anemia.
transcobalamin
transports b12 in circulation, lack of this protein leads to a deficiency.
HGB, AND HCT
decreased macrocytic anemia (>100fL)
reticulocyte increased in macrocytic anemia
likely hemolytic anemia.
blood smear of megaloblastic anemia
macro ovalocytes, dacrocytes, howell jolly bodies, hypersegmentation. Do serum b12 assay.
Folic acid structure
pteridine ring, PABA, glutamatic acid
causes folic acid deficiency
inadequate diet, increased requirement: pregnancy, infancy sickle cell anemia, thalassemia, leukemia; malabsorption tropical and non tropical sprue; Drug inhhibition; bacterial overgrowth in small intestine.
tropical sprue
flattening villie, malabsorption of folate B12.
folate use
donate methyl groups for Nucleic acid synthesis
B12 structure
cobalt atom chelated in middle of chorin ring. cobalamin.
B12 absorption
Rbinder protein binds cobalamin and protects in stomach. rprotein degraded by pangreatic enzymes. Binds IF the IF receptor gets absorbed.
Pernicious Anemia
no IF, no absorption
Pancreatic insufficiency
pancreatic enzymes do not produce sufficient to destroy R binder protein, therefore no absorption.
Transcobalamin 2
B12 transporter. Inadequate TC2 means no less transport, mitotically active cells hampered.
Causes B12 deficiency
Absorption: sprue, gastrectomy, Celiac, Pernicious anemia; Biological competition
Schilling test part 1
Give oral dose radiolabeled B12, flush large non radio labeled. 24 hour urine collection, normal if > 7.5% is collected.
Schillin test part 2
if part one is abnormal, repeat using b12 complexed to IF. If normal, diagnosis is PA. If abnormal, malabsoprtion.
Conversion of THF (important)
requires B12. Also homocysteine to methionine production.
THF function in nucleotide synthesis
THF donates methly grouo for uracil to thymidine conversion.
Homocysteine to MMA to Succinyl COA
requires B12 in last step. This affects fatty acid synthesis. Which can cause neurological disorders and they ususally show up before anemia.
Homocysteine buildup suggests:
B12 or folate deficiency
MMA buildup suggests
B12 deficiency.
normoblastic macrocytic anemia characterized by (determine megaloblastic non megaloblastic from each other)
ROUND not OVAL macrocytes. No howell Jolly Bodies. No hypersegmented neutrophils. No homocysteine or MMA buildup. Polychromasia and MCV between 100-110 fL.
Most common cause macrocytic anemia:
alchoholism. Direct effect on erythropoesis. Liver disease affects RBC surivival and membrane protein composition.
Aplastic anemia
pancytopenia hypocellularity. Can be idiopathic, but if responds to immunosupressants autoimmune. Chloramphenical, insecticides, chemotherapy, ionizing radiation. PNH. Fanconi anemia.
pure red cell aplasia
hypocellularity of only RBC lineage.
Fanconi anemia
many causes some mutations inolved DNA repair. More chromosomal breaks.
Aplastic anemia therapy
transfusion, GCSF, GMCSF, bone marrow transplant, immunosupressive drugs.
Transient erythroblastopenia
occurs after viral infection in children 4 years of age. Pure red cell aplasia.
Chronic renal disease resultts in hypoproliferative anemias
Urea buildup. Dialysis may cause iron and folate deficiency.
Distinguish megaloblastic non megaloblastic anemia
megaloblastic has macroovalocytes, howell jolly bodies, dacrocytes, hypersegmentation.
Most recognizeable megaloblastic sign
hypersegmented neutrophils
megaloblastic bone marrow
decreased M:E, hypercellular. Nuclear maturation defects and asynchrony in all lines.
MMA and homocysteine levels in B12 and folate deficiencies
Homo cysteine elevated in both, MMA only elevated in B12 deficiency.
Gastrin and IF ab in pernicious anemia diagnosis
gastrin is elevated because parietal cells make IF and HCl. When destroyed, decreased HCl causes increased gastrin. Also, anti IF antibodies present in majority of PA.
