Sickle Cell Disease Flashcards
What is Sickle Cell Disease?
An autosomal genetic disorder affecting haemoglobin (that carries oxygen in blood)
Changes the shape of RBCs to sickle shapes instead of healthy biconcave shape
What Sickle Cell Anaemia?
The relative reduction in haemoglobin in RBCs due to change in shape, which can be painful and debilitating
Healthy Haemoglobin
Made of 4 sub-units: 2 alpha helix and 2 beta pleated sheets
Each contain a protein surrounding haem group that contains iron (prosthetic group) and is capable of binding to oxygen
Haemoglobin oxygen binding capacity
Varies dramatically over small oxygen level so that oxygen is readily picked up in lungs but easily given up in tissues
‘Tense’ when oxygen binds poorly and ‘relaxed’ when it binds easily
Sickle Cell Disease Haemoglobin (why change induced)
Single amino acid change in the beta chains so valine replaces a glutamic acid, this produces HbS
Due to single nucleotide change where T replaces A
Thus in ‘tense’ structure haemoglobin molecules polymerise, this distorts structure of RBCs and produces the ‘sickle’ shape
Why is anaemia caused?
Due to re/deoxygenation of sickle RBCs the cell membranes eventually become stiff from stress
This damage causes the cells to last less long in circulation so the disappear faster tan they can be produced in bone marrow
Leading to anaemia (relative lack of haemoglobin)
Other issues (Capillaries)
As sickle cells do not distort well, the capillaries (in which normal RBCs are required to distort to fit through) are occluded/blocked
Thus depriving tissues of oxygen which causes local damage and pain
Sickle Cell Crisis
When events such as infection, dehydration, cold, acid blood or low oxygen in lungs increases polymerisation of sickling it can lead to a crisis
In conjunction with occluded capillaries due to sickle cells
Some positives of sickle cell disease
Helps protect against malaria
Hence its prevalence in African subcontinent
Treatments (4)
Pain relief
Oxygen treatment (increases oxygenation of haemoglobin/ reduces polymerisation)
Some therapies act to stimulate HbF in adults
Tablets of hydroxycarbamide
Investigation
Screening at birth with blood spot test (heel prick)
Genetic screening
But not always apparent at birth as newborns have HbF as well
Psychological/ Social Impacts
Anxiety/ Depression
Life is disrupted in unexpected ways
Debilitating, could lead to inability to work
Biochemistry
HbS- missense mutation causes Val to replace Glu as a result of substitution mutation of T instead of A
Causes haemoglobin to polymerise
Epidemiology
Most common in those with African ancestry (sub-Saharan)
Evolutionary, sickle cell may be selected in these regions as it gives natural resistance to malaria
