Hem & Onc - Pathology (Microcytic Anemia) Flashcards
Pg. 382-383 in First Aid 2014 or 352-353 in First Aid 2013 Sections include: -Microcytic, hypochromic (MCV < 80 fL) anemia
What defines microcytic anemia? How does it appear on blood smear? What are examples of microcytic anemia?
MCV < 80 fL; Hypochromic; (1) Iron deficiency anemia (2) Thalassemias (3) Lead poisoning (4) Sideroblastic anemia (5) Anemia of chronic disease (if progresses to this from normocytic anemia)
What are causes of iron deficiency?
(1) Chronic bleeding (e.g., GI loss, menorrhagia) (2) Malnutrition/absorption disorders (3) Increased demand (e.g., pregnancy)
What metabolic effect does iron deficiency have?
Decrease final step in heme synthesis
What are the lab findings (i.e., iron studies) of iron deficiency anemia?
(1) Decreased iron (2) Increased TIBC (3) Decreased ferritin
What are the blood smear findings of iron deficiency anemia?
Microcytosis and hypochromia
What condition might iron deficiency anemia manifest as? What characterizes this condition?
Plummer-Vinson syndrome; Triad of iron deficiency anemia, esophageal webs, & atrophic glossitis
What is the defect in alpha-thalassemia? What is the result of this defect?
alpha-globin gene deletions; Decreased alpha-globin synthesis
What is key to remember about 1 alpha-globin allele deletion in alpha-thalassemia?
No clinically significant anemia
What is key to remember about 2 alpha-globin allele deletions in alpha-thalassemia?
No clinically significant anemia; However, deletions may be cis or trans (which have important epidemiological implications): Cis deletion prevalent in Asian populations & Trans deletion prevalent in African populations
Cis and Trans deletions are relevant in the case of how many alpha-globin allele deletions? In what populations are cis versus trans deletions prevalent?
2; Cis = Asian, Trans = African
What is key to remember about 3 alpha-globin allele deletions in alpha-thalassemia? More specifically, how much alpha-globin is present and what Hb disease forms?
HbH disease. Very little alpha-globin. Excess Beta-globin forms Beta4 (HbH)
What is key to remember about 4 alpha-globin allele deletions in alpha-thalassemia? More specifically, how much alpha-globin is present and what Hb disease forms?
No alpha-globin. Excess gamma-globin forms gamma4 (Hb Barts). Incompatible with life (causes hydrops fetalis)
What is the disease that results from 4 alpha-globin allele deletions in alpha-thalassemia? What does this mean for the affected patient?
Hydrops fetalis (due to no alpha-globin & gamma4 Hb Barts); Incompatible with life
What causes Beta-thalassemia, and what is the result?
Point mutations in splice sites and promoter sequences; Decreased Beta-globin synthesis
In what populations is Beta-thalassemia prevalent?
Mediterranean
What is one word to describe the genetic makeup of a Beta-thalassemia minor patient? What happens to their Beta chain?
Heterozygote; Beta chain is underproduced
What are the symptoms of Beta-thalassemia minor? What confirms diagnosis?
Usually asymptomatic; Diagnosis confirmed with increased HbA2 (> 3.5%) on electrophoresis
What is one word to describe the genetic makeup of a Beta-thalassemia major patient? What happens to their Beta chain?
Homozygote; Beta chain is absent
What are major signs/symptoms of Beta-thalassemia major?
(1) Severe anemia (due to absent Beta chain) (2) Marrow expansion (“crew cut” on skull x-ray) –> skeletal deformities (e.g., chipmunk faces)
What secondary condition is associated with Beta-thalassemia major, and why?
Secondary hemochromatosis; Severe anemia requires blood transfusion
What can be seen on electrophoresis in Beta-thalassemia major? What can be seen on blood smear?
Increased HbF (alpha2, gamma2); Microcytosis, hypochromia, anisocytosis, poikilocytosis, target cells, & schistocytes
What degree of sickle cell disease is seen in HbS/Beta-thalassemia heterozygotes? On what does this depend?
Mild to moderate; Amount of Beta-globin production
What effect does lead have on heme synthesis, and how?
Decrease; Lead inhibits ferrochetelase and ALA dehydratase
What is the classic blood smear finding in lead poisoning, and why?
Basophilic stippling; Lead inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA
What is a high risk to keep in mind for lead poisoning?
Houses with chipped paint
What are the clinical findings in lead poisoning? What is the first line treatment for lead poisoning? What is a good mnemonic to remember these things?
(1) Lead Lines on gingivae (burton’s lines) & on metaphyses of long bones on x-ray (2) Encepalopathy (3) Erythocyte basophilic stippling (4) Abdominal colic (5) sideroblastic Anemia (6) Drops - foot and wrist drops; Dimercaprol and eDta; LEAD (which is really more like LLEEAADDD)
What is used for chelation for kids in cases of lead poisoning?
Succimer
What is the defect in sideroblastic anemia? More specifically, what is the mutation and mode of inheritance?
Heme synthesis (due to protoporphyrin deficiency); X-linked defect in deta-ALA synthase gene
What are the general types of causes of sideroblastic anemia?
(1) Genetic (2) Acquired (myelodysplastic syndrome) (3) Reversible (alcohol is most common, lead, vitamin B6 deficiency, copper deficiency, isoniazid)
What causes the appearance of ringed sideroblasts?
Iron-laden mitochondria (due to protoporhyrin deficiency)
What are the lab findings (i.e., iron studies) in sideroblastic anemia?
(1) Increased iron (2) Normal TIBC (3) Increased ferritin
How is sideroblastic anemia treated, and why?
Pyridoxine (B6, cofactor for delta-ALA synthase, which is what is affected in sideroblastic anemia)
Name a physical exam finding commonly indicative of anemia.
Conjunctival pallor
What kind of condition serves as an acquired cause of sideroblastic anemia?
Acquired (myelodysplastic syndromes)
What are 5 reversible causes of sideroblastic anemia? Which is most common?
Reversible (alcohol is most common, lead, vitamin B6 deficiency, copper deficiency, and isoniazid)
