page 1- Flashcards
sickle cell is a
monogenetic condition
it is cause by a
single base mutation
when was it discovered
in 1910
what is the result of the disease?
it is the result of homozygous and compound heterozygote inheritance
of a mutation in the β-globin gene
What does this mutation causes?
A single base-pair point mutation (GAG to GTG) results in the
substitution of the amino acid glutamic acid (hydrophilic) to Valine (hydrophobic) in the 6th position
of the β-chain of haemoglobin referred to as haemoglobin S (HbS
common type of sickle cell
The inheritance of homozygous HbS otherwise referred to as sickle cell anaemia (SCA) is the most
predominant form of SCD
sickle cell
in certain regions 1/4 individuals are carriers of the disease.
in LICs
50-90% die within first 5 years
causes of young death
Among the common causes of death in the absence of
early diagnosis followed by education and preventive therapies such as penicillin prophylaxis and
regular surveillance include infections, severe anaemia (acute splenic sequestration, aplastic anaemia)
and multi-organ failure
what happens to the RBCs
when
exposed to deoxygenated environment undergo polymerisation and become rigid
what do the RBC causes
The dense rigid RBC’s lead to vaso-occlusion, tissue ischaemia, infarction as well as
haemolysis
complications
complications such as leg ulceration, stroke, pulmonary hypertension and priapism
RBCS lifespan of SCD
10-20 days due to Haemolysis
what affects the individual with SCD
Pain. this leads to many hospital visits. it is unpredictable.
Pain causes
Pain occurs due to stimulation of nociceptive nerve fibres caused by microvascular occlusion. The
microcirculation is obstructed by sRBCs, thereby restricting the flow of blood to the organ
pain in infants
Infants display their pain
nonverbally with irritability and apparent ‘regression’ tendencies such as inability to weight bear, walk
or crawl.
triggers to pain
The onset of
pain is spontaneous, usually no precipitating factors; well-known triggers include infections, fever,
dehydration, acidosis, sudden change in weather including wind speed, cold, rain and air pollution.
Resolution of pain is unpredictable. Acute pain might lead to chronic pain
diseases
SCD increases susceptibility to infections, notably bacterial sepsis and malaria in children under
five years
social effects of SCD
SCD has a significant psychosocial impact on patients and families [53]. This mainly results from
the effect of pain and symptoms on their daily lives, and society’s attitudes towards them. Cultural
factors are particularly important to these problems because of beliefs and practices [54]. Furthermore,
the ability of people with SCD to cope with their condition varies greatly because severity, general
health, and quality of life varies greatly among individuals [5
Treatment
SCD causes a range of acute and long-term complications, requiring a multi-disciplinary approach,
involving various medical specialists. In the United Kingdom, comprehensive SCD care is coordinated
by specialist haemoglobinopathy teams
Education
Such teams play a key role in education about SCD for
patients and their families, as well as guiding treatment with disease-modifying therapies, access
to psychology, social and welfare support
mild pain
can be dealt at home .
self psychological help.
medical treatment so far
Currently the only available disease-modifying medications for SCD are hydroxycarbamide and
l-glutamine.
Another effective disease modifying therapy is blood transfusion to raise the haemoglobin
for improved oxygenation in severe anaemia and also to reduce the proportion of sickle haemoglobin
(HbS%) may be give as a simple top-up blood transfusion or as exchange transfusion (manual or
automated).
The main curative therapy is stem cell transplantation while gene therapy is in the horizon
in clinical Trials
Hydroxycarbamide
reduces the number of leucocytes in blood, and reduces
expression of surface adhesion molecules on neutrophils, red cells and vascular endothelium resulting
in improved blood flow and reducing vaso-occlusion
