Sickle cell disease Flashcards
Describe the sickle gene:
Mis-sense mutation at codon six for the B globin chain
Glutamic acid replaced with valine
Glutamate is polar and soluble where valine is insoluble and non-polar - this distorts the shape.
HbS polymerises to form fibres - tactoids
Autosomal recessive disorder - clinically heterogeneous
What is the effect of the sickle cell genes of red cells?
Distortion:
-polymerisation form oxyHbS - initially reversible but following this is it not.
Dehydration
Increased adherence to vascular endothelium - mainly post-capillary venules
Rigid
What is the epidemiology of SCD in the UK?
In greater london is the most prevalent
12000 - 150000
Describe the pathogenesis of SCD:
Shortened lifespan - haemolysis:
- Anaemia
- Gall stones
- Aplastic crisis
Reduced erythropoiietic drive as hbS is a low affinity hb.
Blockage to microvascular circulation:
- Tissue damage and necrosis (infarction)
- Pain
- Dysfunction
Nitric oxide is depleted in bioavailability as it is scavenged by the Hb–> this can lead to pulmonary hypertension as NO leads to the dilation of blood vessels.
What are the organs affected by SCD?
Spleen - hyposplenism
Bone/joints -osteomyelitis (infection of the bone)
Skin - chronic /recurrent leg ulcers
Lungs - acute chest syndrome, chronic damage, pulmonary hypertension
Urinary tract - haematuria, impaired conc of urine, renal failure, priapism
Brain - stroke, cognitive impairment
Eyes - proliferative retinopathy.
What are the early presentation of sickle cell disorders?
Symptoms rare before 3-6 months
Onset coincides with change from fetal Hb to adult Hb
Dactylitis - sausage finger –> inflammation of a single digit - can be painful.
Splenic sequestration - RBC gets stuck in the spleen and causes it to enlarge
Infection - S. pneumoniae
What are the sickle emergencies?
Septic shock
Neurological signs or symptoms
Priapism - persistent and painful erection of the penis (greater than 4 hours)
Symptoms/signs of anaemia with Hb (drop from 0 to 30 must be tackled)
What are the lab signs of SCD?
………….
How do you diagnosis SCD?
In the presence of reducing agent oxyHb converted to deoxy Hb
Solubility decreases
Definitive diagnosis - electrophoresis
What is the management of SCD?
Folic acid
Penicilin
Vaccination
Monitor spleen size
Blood transfusion for acute anaemic events, chest syndrome and stroke.
Pregnancy care
Exchange transfusions: stroke, acute chest syndrome
Haemopoietic stem cell transplantation
Introduction of HbF –> hydroxyurea + Butyrate (short half life and so have to be given IV)
What are the triggers of painful crises?
What are the methods for pain management?
- Pain relief (opoids)
- Hydration
- Keep warm
- Oxygen in hypoxic
- Exclude infection -> blood and urine cultures, CXR
Individual analgesia protocols, patient controlled analgesia, adjuvants e.g. paracetamol.
What are the current disease modifying strategies?
Describe hydroxyurea (hydroxycarbamide) mechanism of action:
Increases the production of fetal hb
Decreases stickiness
Reduces WBC production
Improves hydration
Generated NO
Describe haemopoeitic stem cell transplantation and what it is used for:
CNS disease
……………..
