sickle cell disease Flashcards
what base substitution occurs in HbS?
charged glutamic acid to uncharged valine at position 6
what does a Hb molecule consist of?
2 alpha and 2 beta chains
what does deformation of erythrocyte lead to?
vascular occlusion, leading to sickle cell anaemia
what genetic makeup causes sickle cell anaemia?
HbSS
what genetic makeup causes sickle cell trait?
HbAS - oxygen affinity is the same (asymptomatic)
what genotype gives symptomatic sickle cell?
HbSS - homozygous
what happens to the reticulocyte count in sickle cell disease?
It’s increased as a compensatory mechanism due to elevated levels of haemopoiesis
what is splenomegaly?
Arises in patients with SCD (accumulation of degraded erythrocytes increases size of spleen)
how does sickle cell anaemia lead to vision loss?
Sickle cell ischaemia –> releases chemokines –> angiogenesis of collaterals to maintain oxygen to retina (easily damaged) –> spread across the eye
what is an ischaemic stroke?
cerebral artery is blocked resulting in oxygen deficiency
what can cause a sickle cell crisis?
Cold weather, strenuous exercise, stress and dehydration
why are sickle cells susceptible to damage?
have a shorter lifespan due to rigid sickle structure
symptoms of sickle cell disease
anaemia, acute chest syndrome, bone crises, visual loss, gallstones, ischaemic/haemorrhagic stroke, jaundice, splenomegaly , priapism, splenic sequestration, kidney damage
what causes vision loss?
Sickle cells accumulating within the microvessels in retina, increasing pressure and consequently damaging vessels
what causes an ischaemic stroke?
cerebral artery blocked due to sickling resulting in oxygen deficiency
what causes a haemorrhagic stroke?
occurs due to angiogenesis (formation of new blood vessels), collaterals are easily broken
what type of stroke is asymptomatic?
silent strokes
what is a microvascular occlusion?
reduced flow to the bone marrow
what are some patient triggers of a vaso-occlusive crisis?
cold weather, strenuous exercise, dehydration
explain the mechanism that causes a bone crises
reduced blood flow to the bone marrow due to sickling within blood vessels, resulting in microvascular occlusion.
oxygen depreivation –> subsequent prolonged ischaemia leads to infarction –> further exacerbate sickling (dehydrogenation)
outline the sickle solubility test
blood is taken; sodium dithionite is added; Hb is released, HbA dissolves easily in blood plasma; HbS is less soluble and solution will become turbid
what causes gall stones and what type of symptom is it?
bilirubin release; chronic
What is dactylitis?
acute crises –> pain in hand joints, blood vessels are occluded by sticky red blood cells –> reduces oxygen being delivered
what is splenic sequestration?
Large volume of blood pooled in spleen - sudden drop in Hb
In electrophoresis what region is closest to the anode?
HbA
What causes HbS to be further away from the anode?
Valine is uncharged whereas glutamate is negatively charged therefore it is more attracted to the anode.
Why is the sickle solubility test not that effective?
The test does not differentiate between sickle cell trait (AS) and SS
what is the purpose of screening?
So that genetic counselling can be provided to couples that are both carriers to provide awareness of the possibility for a homozygous newborn
What is used to screen newborns and how is it done?
Haemoglobin isoelectric focusing (Hb IEF); by taking a heel-prick sample of blood
List some treatments of sickle cell disease
Blood transfusions, hydroxycarbamide, bone marrow transplant, gene therapy, daily doses of antibiotics; children should have all routine vaccines
what may multiple blood transfusions lead to?
Hemosiderosis, which damages liver, heart, pancreas and other organs, leading to diabetes mellitus
Give an adverse effect of using opioids
highly addictive
give an adverse effect of using hydroxycarbamide
increases risk of infection
what can be used to treat crises?
painkillers (ibuprofen and aspirin), severe pain treated using opioid daily medications
How can crises symptoms be alleviated?
constant hydration, keeping warm, avoiding locations exposed to high altitudes and low oxygen levels
Explain how hydroxycarbamide works and what it does
Stimulates synthesis of HbF. Hydroxyurea further suppresses marrow production of reticulocytes and neutrophils (reduces vaso-occlusion since neutrophils promote vascular adhesion).
What do neutrophils promote?
vascular adhesion
who is considered for a bone marrow transplant?
patients severely suffering from disease, are young and have a matched sibling
List some patient triggers of a vaso-occlusive crisis
Cold weather, strenuous exercise, dehydration, stress
What increases sickling?
acidosis, low flow blood vessels
