Sicle Cell Disease Flashcards
What base substitution occurs in HbS
Charged glutamic acid changed to uncharged valine at position 6
What does Hb molecule consist of
2 alpha and 2 beta chains
What genetic makeup causes sickle cell anaemia
HbSS
Autosomal recessive
What genetic makeup causes sickle cell trait
HbAS oxygen affinity is the same
Asymptomatic
What happens to the reticulocyte count in SCD
increases as a compensatory mechanism due to increased levels of haemopoeisis
What is splenomegaly
Increase in size of spleen due to accumulation of degraded erythrocytes
How does sickle cell anaemia lead to vision loss
Sickle cells accumulate within micro vessels in retina increasing the pressure and damaging vessels
Vision loss
Sickle cell ischaemia-released chemokines-angiogenesis of collaterals to maintain oxygen to retina-spread across eye
What is an ischaemic stroke
Cerebral artery is blocked resulting in oxygen deficiency
What causes a sickle cell crises
Cold weather
Strenuous exercise
Stress
Dehydration
Microvascular occlusion caused by
When sicklesd red blood cells block small blood vessels
Bone crises mechanism
Reduced blood flow to bone marrow due to sickling reuksting in microvascukar occlusion
Oxygen deprivation-subsequent prolonged ischaemia-infarction-sickling
Sickle solubility test
Add sodium dithionite
Hb is released
HbA dissolves easily in plasma
HbS less soluble and causes solution to become turbid
Can’t differentiate between HbSS and HbAS
What causes gall stones
Billirubin release
Splenic sequesteration
Large volume of blood pooled in spleen
Sudden drop in Hb
In electrophoresis
HbA closest to anode
HbS further away as valine is uncharged so less attracted to anode
In sickle cell anaemia HbS is thick whereas not present if you don’t have the disease
Carried out on cellulose acetate gel
Why is sickle solubility test not that effective
As it doesn’t differentiate between sickle cell trait and sickle cell anaemia
What is used to screen newborns
Heel prick test
Treatments
Blood transfusion
Hydroxycarbamide
Bone marrow transplant
Gene therapy
Antibiotics
How does hydroxycarbamide work
Stimulates synthesis of HbF
Suppresses marrow production of reticulocytes and neutrophils
Globin chains contain
HbA: two alpha, two beta.
HbA2: two alpha, two delta
HbF (Fetal Haemoglobin): two alpha, two gamma.
What causes sickling
During deoxygenation hydrophobic valine protrudes from the surface causing interactions between valine on one molecule with phenylaline leucine and alanine
Haemolysis
Repeated sickling weakens cell membrane
Results in intravascular haemolysis
Sickle cells only last for 20 days reuksting in anaemia
Crispr
Cas9 enzyme can target and repair the faulty B Globin gene
Cas9 promotes the production of fetal haemoglobin by breaking a gene that encodes a repressed
Intravascular Haemolysis
When a red blood cell ruptures
Myoglobin
Is an oxygen binding protein found in muscle
Positive cooperation
Once an oxygen molecule binds to haem it becomes easier for the next oxygen molecule to bind
Vasocclusion
Blockage of capillaries
What to they have an increased susceptibility to
Encapsulated bacteria
Zolas triggers
Interpersonal crises eg divorce/death
Perceived interference with social/personal relations(affects social life)
Sanctioning (pressure from others)
Perceived interference with vocational/physical activity eg affecting job
Temporalizing of symptomatology eg setting deadlines
Hellman’s folk model
What happened
Why has it happened
Why me
Why now
What would happen if nothing was done about this
