3. Sickle Cell Disease Flashcards
life expectancy of scd
uk = 40-60yrs
devleoping nations = 50-90% childhood mortality
balanced polymorphism
- multiple alleles of a gene are maintained in a population
- one version will have an advantage compared to the other
genetic cause of scd
A->T
glutamic acid –> valine on 6th position of beta globin chain
name of heterozygous and homozygous states
het = HbAS
homo = HbSS
frequency of HbAS in malarial areas
up to 40%
provides protection
one major theory as to why HbAS provides malarial protection
- their sickle Hb has altered interaction with actin in a RBC
- means RBC cytoskeleton is altered
= ‘sticky’
-These changes may impair parasite-induced remodelling of the red blood cell surface membrane - means they cant complete their life cycle efficiently
difference between glutamine and valine
glu is + charged
(so moelcules repel each other)
val is neutral (acc promotes interaction)
when and why does valine cause Hb to stick together
- Hb is deoxyegnated
= valine exposed on Hb surface - now can interact cuz valine neutral charge
- forms long fibrous linked chains
how come most dont have sickling all the time
- process of sickling takes time
- most cells return to lung and get o2nated before major sickling occurs
how come foetuses are chilling
foetal Hb is not affected
sickling only happens after delivery
what is a coinherited factor that can decrease disease severity
hereditary persistence of foetal haemoglobin (HPFH)
CHRONIC DAMAGE: Hb
repeated cycles of polym damages Hb
eventually polym starts to prolong
and doesnt reverse = Hb denatures
CHRONIC DAMAGE: cells
repeated cycle of cell shape change damages cell
- causes partial shape change
- memb pumps damaged = cell dehydrated
4 types of cell appearances
- boat cells = partial sickle change
- target cells = Hb pool
- dehydrated dense and irregular damaged (MOST COMMON)
- true sickle cells = irreversible sickling
