Defects of Globin synthesis Flashcards
What is quantitative globin defect
Not enough globin chains are made. Includes thalassemia
What is qualitative globin defect
Correct number of globin chains but they function abnormally. Hemoglobinopathy
HbA chain makeup
2 alpha and 2 beta chains
HbA2 chain makeup
2 alpha and 2 delta chains
HbF chain makeup
2 alpha and 2 gamma chains
What is thalassemia
Deletion or inactivation of globin chain gene that leads to decreased production of one or more globin chains
Causes of thalassemia
full or partial gene deletion, point mutations
Complications of thalassemia
decreases Hb production, overproduction of non-affected globin chains, disrupts ratio of chains, hypo micro anemia
How many loci of alpha chains and what chromosome
4 loci, chromosome 16
How many loci of beta chains and what chromosome
2 loci, chromosome 11
What globin chains in HbH
4 beta chains
What globin chains in Hb Barts
4 gamma
What hemoglobins can be made in alpha thalassemia
HbH and Hb Barts
What problems arise with HbH and Barts?
Unstable so inc rate of precipitation in cytoplasm. High O2 affinity, and carries an insignificant amount of O2
What is HbH stained with
Brilliant cresyl blue
Hydrops fetalis
Incompatible with human life. Occurs when there are 4 alpha chain deletions.
Silent beta thalassemia
Partial deletion of one gene. Asymptomatic, no detectable anemia
Minor beta thalassemia
1 deletion, asymptomatic unless there is a significant stressor like illness or surgery
intermediate beta thalassemia
partial deletion of one or more genes, moderate anemia
Major beta thalassemia
2 deletions, called cooleys anemia
What hemoglobins are associated with Beta thalassemia
HbA2 and HbF
Peripheral blood picture of beta thalassemia
nRBC, tear drop, target cells, baso stippling, hypochromia, microcytosis, schistocyte, ovalocyte, siderotic granules, Howell-jolly
Blood pic for minor beta thalassemia
mild hypo micro, targets, ovalocytes, tear drops and baso stippling
What happens with an increase in EPO
Erythroid hyperplasia, increased cellularity in the bone marrow. Can cause frontal bossing
What amino acid substitution is in sickle cell anemia?
Valine is substituted for glutamic acid
Difference between sickle cell trait and sickle cell anemia
Trait has 1 mutated beta gene, is heterozygous and less severe. Usually no sickle cells on smear
Anemia has 2 mutated beta genes, homozygous and extremely severe. Always sickle cells on smear
Characteristics of sickle cell in peripheral blood
sickle, target, nRBC, inclusions
Bone marrow in sickle cell anemia
reticulocytosis, hyperplasia
Acute chest syndrome
Symptoms: fever, respiratory, lung infiltrates
Second most common cause of hospitalization. Occurs within 1-3 days of vasoocclusive crisis
Other complications of sickle cell
Autosplenectomy, aplastic crisis, massive extravascular hemolysis
Hemoglobin C disease substitution
Lysine is substituted for glutamic acid
Hemoglobin C disease blood picture
Pocketbook cells with junky looking target cells
Hemoglobin SC disease
marriage of HbS and HbC with dense pointy irregular crystals and moderate hemolytic anemia
Beta thal minor Hb production
less total HbA than normal
Sickle cell trait Hb creation
More HbA than HbS
Beta thal minor / sickle cell trait Hb production
More HbS than HbA
How are defects of globin synthesis diagnosed
Hemoglobin electrophoresis, global prevalence etc
Differential diagnosis alpha vs beta thalassemia
Alpha: symptoms at birth. Cant make HbF, 3+ deletions only
Beta: no symptoms until 6 months. Large amounts of HbF until then
