Sickle-Cell Anaemia Flashcards
What is the consequence of the mutation in the beta-globin gene?
Sticky hydrophobic pocket created by valine substitutions
Hb polymerises when in the T form (aggregation —> sickled cells)
What is the genetic mutation leading to sickle-cell anaemia?
Single Base Substitution: A —> T
Glutamate (charged, hydrophilic) —> Valine (uncharged, hydrophobic)
Mutation in beta-globin gene
How does the HbS O2 saturation curve differ to normal Hb?
Shift to the right (lower O2 affinity)
Therefore lower saturation of Hb
More O2 released at same pO2
What is the inheritance pattern of sickle-cell?
Autosomal recessive
Carrier = sickle-cell trait
Why is sickle-cell anaemia so common, despite being a recessive mutation?
Carrier status confers protection against malaria
Therefore selective advantage for allele in malaria-ridden areas e.g. Africa
In what parts of the body will you find sickled cells?
Low pO2 e.g. tissue blood flow (T form predominates)
Why does anaemia result from sickle-cell disease?
Premature lysis of deformed/weakened sickled cells by spleen —> decrease in Hb
(haemolytic anaemia)
What is the lifespan of the sickled RBCs compared to normal RBCs?
Normal = 120 days
Sickled = 10-20 days
How can the body adapt to chronic anaemia?
- increase in tissue blood flow
- lower O2 binding affinity of HbS means that tissues are still well-supplied with O2
Why does sickle-cell disease cause jaundice?
Haemolytic anaemia —> haem broken down —> increased bilirubin
Bilirubin > renal threshold —> spills into bloodstream
Why does sickle-cell disease cause gallstone formation?
Increased bilirubin produced —> increased bilirubin in bile —> pigment gallstones —> biliary colic (pain due to obstruction of bile duct)
What are the complications of frequent occlusion of blood vessels?
Decreased blood flow to skin —> leg ulcers (open sore caused by break in skin/mucous membrane)
Bleeding in retinal veins/retinal detachment —> blindness
What are some other chronic effects of sickle-cell disease apart from gallstones and frequent occlusion-related conditions?
Priapism (persistent erection —> impotence)
Splenic crisis
Acute chest syndrome
Where is the spleen located anatomically? What are its functions?
Superolateral left upper quadrant
- lymphocyte proliferation
- immune surveillance & response
- lysis of old RBCs (recycling of haem)
What is an acute sickle-cell crisis?
Increased T form of RBCs —> more sickling in tissue capillaries —> occlusion —> infarction (ischaemia due to inadequate oxygen & nutrient supply -> PAIN) —> necrosis (tissue death) —> scar tissue formation
note: restore blood flow quickly to attempt to reverse
What are some common areas of occlusion during an acute sickle cell crisis? What can this lead to?
- bone
- pleura
- brain —> STROKE
- kidney —> KIDNEY FAILURE
- spleen —> SPLENIC CRISIS
What is a splenic crisis?
(spleen sequesteration)
ACUTE:
Sickled cells pool in spleen —> vaso-occlusion of blood vessels in spleen (blood not circulating in spleen)
Splenomegaly to try and compensate
Sudden, severe anaemia and drop in heart rate
CHRONIC:
Damaged spleen —> fibrosis
Auto-splenectomy (body removes non-functional spleen) —> decreased lymphocyte production —> increased risk of infection
What is acute chest syndrome?
Sickling in lung capillaries —> fever, pain, violent wheezing cough —> pulmonary hypertension —> heart failure
What are some of the factors which can precipitate an acute sickle-cell crisis?
- hypoxia (low pO2 —> more T form RBCs —> more sickled cells which block vessels)
- dehydration (increased polymerisation of T form)
- infection (stresses body reserves; can cause hypoxia and dehydration)
- low environmental temp. (vasoconstriction - occlusion - increased O2 binding affinity)
- low pH —> increased [H+] —> increased T form
What is the prevention (conservative) management of sickle-cell disease?
Avoid factors precipitating a crisis
Prophylactic antibiotics & vaccinations (especially with spleen dysfunction & removal)
Frequent eye exams (screen for retinopathy)
Folic acid (prevent severe anaemia)
Direct line to hospital
What is the therapeutic (medical) treatment for sickle-cell disease?
Blood transfusion for anaemia (to reduce risk of stroke by increasing [HbA]:[HbS]) —> chelation therapy if this leads to iron overload
Crisis treatment:
- analgesia (opioids, anti-inflammatories, vasodilators e.g. NO)
- oxygenate & hydrate (to increase R:T)
- antibiotics if cause is infection
- blood transfusion
What is the surgical treatment for sickle-cell disease?
Splenectomy for splenic crisis
Chemotherapy (destroy bone marrow and replace with stem cell transplant for normal RBC production) (children only)
