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Flashcards in CPS - Sickle Cell Deck (13)
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What mutation occurs in sickle cell disease?

Single base substitutions in Hb beta chain from A to T

Changes glutamate to valine


What impact does changing glutamate to valine in sickle cell disease have?

1). It makes the transition from tense form to relaxed form less likely
= binds less O2
= releases O2 at lower pO2

2). Valine is neutral (glutamate negative) therefore is hydrophobic
= sticky hydrophobic pocket of Hb forms. This distorts the RBCs = weakened membranes = more likely to lyse or be broken down by the spleen.


How does anaemia occur in sickle cell and what is its effect?

Increased breakdown of sickled RBCs = less Hb = less O2 being carried.

Has little effect because instead, tissue blood flow increases and Hb shifts more towards the tense state, so it will release O2 easier.


How does jaundice occur in sickle cell patients?

Jaundice can occur as increased breakdown of RBCs leads to more Hb being in the spleen. This is then conjugated into bilirubin.
More Hb therefore = more bilirubin, and this can accumulate.


What conditions increase sickling of cells?

Low pH of blood


How can blood clots occur in sickle cell disease and what can this lead to?

Sickle cells are less flexible, so can't pass through small capillaries like RBCs can. This means they can end up blocking the capillaries, leading to tissue necrosis and infarction.


What are the long term effects of sickle cell disease?

Gallstones - high levels of bilirubin
Less immunity - overactive spleen = function is reduced.
Leg ulcers, bone necrosis, blindness and renal disease all occur as a result of capillary blockages.


How does coldness contribute to sickle cell crisis?

Vasoconstriction of capillaries = even harder for sickled cells to pass through


How does hypoxia worsen sickle crisis?

Sickled cells already have reduced ability to carry O2, so hypoxia exacerbates this issue = more Hb likely to be in T state = terminal valine exposed = aggregation = blockage


How is sickle cell crisis managed?

Manage any infections
Avoiding factors that lead to the crisis


What causes RBCs to distort in sickle cell crisis?

Hb aggregates and keeps shifting from the tense to relaxed form. This puts the RBC membranes under constant stress, so eventually they remain distorted.


How does dehydration contribute to sickle cell crisis?

More likely for Hb in T state to aggregate as there is less plasma. Also makes blood more viscous = clots more likely = crisis.


How does acidosis lead to sickle cell crisis?

More H+ causes decrease in Hb affinity = more Hb likely to be in T state = terminal valine exposed = aggregation = blockage