BIIC Pathology Lecture 2_Sickle Cell Anemia and Thalassemias Flashcards
What are hemoglobinopathies?
They are a group of hereditary disorders that result in structuraly abnormal hemoglobin
What is the prevelance of sickle cell anemia?
In parts of Africa with endemic malaria, geen frequency reaches 30%. In the United States, 8% of African Americans are heterozygous carriers
What causes sickle cell anemia?
A single amino acid substitution at the 6th residue of Beta globin changes glutamate to valine and replaces HbA with HbS
What are the two major pathologic results of sickle cell?
1) Chronic moderately severe hemolytic anemia (sRBC have a mean life span of 20 days)
2) Vascular obstruction that can cause pain, ischemic tissues, strokes, and damage to any organ
How does the body try to compensate for chronic anemia, as is seen in sickle cell?
1) increase medulary space where hematopoiesis is occuring. This can lead to prominant cheek bones and the “crew cut” sign on an xray
2) Extramedulary hematopoiesis in the liver and spleen
What is the apperance of the spleen in a patient with sickle cell?
Children have splenomegaly but adults have small fibrotic non functional spleens (autosplenectomy)
When do signs of sickle cell anemia begin to occure?
At about 6 months of age when HbF is replaced by HbA
What are the most common Vasoocclusive crises associated with sickle cell anemia?
• Hand-foot syndrome, resulting from infarction of bones in the hands and feet,
is the most common presenting symptom in young children.
• Acute chest syndrome, in which sluggish blood flow in inflamed lung (eg, an
area of pneumonia) leads to sickling within hypoxemic pulmonary beds.
• Stroke, which sometimes occurs in the setting of the acute chest syndrome.*
• Proliferative retinopathy, a consequence of vasoocclusions in the eye that can
lead to loss of visual acuity and blindness.
What is the main therapy for Sickle Cell Anemia?
Hydroxyurea
What chromosomes code for adult globin molecuels?
Two regions on chromosome 16 code for alpha-globin. One region on chromosome 11 codes for Beta globin
What is the difference between Beta0 and Beta+ thalassemias?
Beta0 produces no beta globin. Beta+ produces reduced amounts of beta globin
What type of mutation causes beta thalassemias?
Typically it is a single base change, often that leads to abnormal RNA splicing
What are the two ways Beta thalassemia contribute to anemia?
1) fewer functional beta globins leads to microcytic and hypocromatic cells (because there is less HbA than normal)
2) Unpaired alpa globin form toxic precipitates and that kill erythroid precursors leading to fewer RBC reaching maturity
What does ineffective hematopoiesis lead to (think Fe)
Low hepcidin which leads to iron overload. This is because you do not have enough RBC so you body tries to make more and thinks it needs iron to accomplish that. In reality you have tons of iron your RBCs just dont reach maturity
What type of mutation causes an alpha thalassemia?
deletions in one or more of the alpha globin genes. Severity of the condition is directly proportional to how many alpha globin genes are effected. If all 4 are disfuntional, the condition will be lethal in utero because HbF is not formed and Beta4 and gamma4 have a high O2 affinity and do not deliver O2 to the tissues
