Hemaglobinopathies Flashcards
What comprises 70% of the RBC?
hemoglobin
Where are the beta globin genes located?
short arm of chromosome 11
What genes are located within the “beta globin gene cluster”?
genes for beta, delta, gamma-A, gamma-G and epsilon globin
What controls expression of the “Beta Globin Gene Cluster”?
A single locus control region
T/F: All globin genes on chromosome 11 are continuously expressed.
F: genes are differently expressed throughout development
What results from rearrangement, deletion or changes to the genes within the Beta Globin Gene Cluster?
gene expression during improper stages of development
What genes are within the Alpha Globin Gene Cluster?
Zeta 1 and 2
Alpha 1 and 2
What does gamma gene expression yield?
Hgb F
What does expression of the delta gene yield?
Hgb A2
What does expression of the beta gene yield?
Hgb A
What are the components of the tetrameric hgb protein?
Products of B1, B2 genes
Products of any 2 of the 4 alpha genes
What are the 4 functions of hgb?
- O transport
- CO2 transport
- pH regulation
- NO sump
NO is inhibited by (3):
hypoxia
activated WBCs
Sickled RBCs
What activates sickled RBCs?
hypoxia
What is ultimately activated by hypoxia (via a few different pathways)?
VCAM-1
What is inactivated by NO (either directly or indirectly)?
VCAM-1
In the presence of Heinz bodies, what will be impaired?
Vasodilation, due to removal of NO
Explain how beta-like globin gene switching progresses during development.
- Initially, epsilon is expressed.
- As epsilon expression decreases, gamma (A +G) are expressed.
- Just before birth, gamma expression declines and beta expression increases.
(4. Delta is expressed a little bit, starting around birth)
What happens to unstable hgb (such as Heinz bodies) within the RBC?
it precipitates
Sickle cell is commonly seen in people of what descent?
African
Mediterranean
What are two types of Sickle Cell variants (non-carriers)?
Sickle Cell Anemia
- Hb SS - Hb SB<sub>0 </sub>Thalassemia
Hb SB+ Thalassemia
Sickle Hb SC (mildest)
T/F: Hb SC has partially normal hgb
F: no normal hgb
What percent of AA are Hgb-AS heterozygous?
8%
If a patient has more symptomatic sickle cell, he/she is higher risk for:
early death
What is the cardinal feature of sickle cell disease?
unpredictable pain
What sickle cell symptom often signals life-threatening complications? What are these?
Acute pain (“precedes 22% of SCD deaths”)
Chest syndrome, stroke, sepsis, organ failure