Haemoglobinopathies Flashcards
1
Q
What can sickle cell and thalassaemia be described as?
A
- Sickle cell disease can be described as qualitative disorder, as haemoglobin is being produced, but it is of a poor quality
- Thalassaemia’s can be described as quantitative disorders. Insufficient haemoglobin is being produced.
2
Q
What are the key features of RBC’s?
A
- Erythrocyte have a biconcave disc structure and are 7.2 by 2.2 microns in size.
- They have no nucleus
- They are basically a membranous sack, packed with the bright red pigment called haemoglobin.
- Haemoglobin enables the cells to carry oxygen and carbon dioxide.
- The structure of the red blood cell and the fact that they have no nucleus makes them deformable.
- This deformability is important as it allows the cells to squeeze through the microcirculation.
- The cell membrane has a lipid bilayer structure in which the membrane proteins are found.
- Normal red blood cells last approximately 120 days.
- RBC membranes
o 2 layers of fat (phospholipids) help to maintain shape of cell
o regulate sodium and potassium levels within cell
o maintain osmotic pressure of blood.
3
Q
What are the key features of haemoglobin?
A
- HAEM (iron)
- GLOBIN (protein)
- 4 main globin chains are - alpha, beta, gamma, delta
- Globin contains approx.. 140 amino acids (alpha -141, beta - 146)
- Alpha - chromosome 16
- Beta, gamma, delta - chromosome 11
- One haemoglobin (Hb) molecule consists of four haem-globin combination arrange in two functional pairs e.g. 2 alpha and 2 beta
- In a haemoglobin molecule the four subunits are arrange so that they touch one another
- One Hb molecule can carry 4 molecules of O2.
- Amount of O2. carried depends on amount of oxygen surrounding the molecule (i.e. the partial pressure of O2.).
4
Q
Proportions after one year of life:
A
- Hb A - 96% of Hb after one year
o 2 Alpha chains and 2 Beta chains. - Hb A2 - 2-3% of all adult Hb
o 2 Alpha chains and 2 Delta chains. - Hb F – below 2% of adult Hb after one year. Made up of 2 Alpha chains and 2 Gamma chains.
5
Q
Thalassaemia
A
- Caused by the inheritance of a defective alpha or beta globin gene.
- Results in reduced rate of globin chain formation and RBC with inadequate Hb content.
6
Q
Signs and symptoms of thalassaemia?
A
- Weakness and fatigue
- Pale appearance
- Abnormal swelling
- Abnormal borne structure in the face and skull
- Heart problems
- Iron overload
- Slow growth
7
Q
What is Alpha Thalassaemia?
A
- The alpha chains are produced by four genes, two on each chromosome 16, inherited as pairs. The severity of the condition will depend on how many of those genes have been altered.
- If one gene is mutated, there’s little or no effect. If two genes are mutated (one on each chromosome), there may be symptoms of mild anaemia. This condition is known as the alpha thalassaemia trait.
- If two people with the alpha thalassaemia zero trait (when two genes on the same chromosome are altered) have a child, there’s a one in four chance of the child inheriting the most severe form of alpha thalassaemia.
- If three genes are mutated, the result will be a condition called haemoglobin H disease. Someone with this condition will have lifelong (chronic) anaemia and may require regular blood transfusions
- If all four genes are mutated, the result will be the most severe form of alpha thalassaemia, known as alpha thalassaemia major. Infants with this condition are unable to produce normal haemoglobin and are unlikely to survive pregnancy.
8
Q
What is beta thalassaemia?
A
- Unlike alpha genes, there are only two beta genes, one each on chromosome 11.
- Beta thalassaemia can range from moderate to severe. The most severe form of the condition is known as beta thalassaemia major (BTM), where both beta genes are affected. People with BTM will require blood transfusions for the rest of their life.
- Beta thalassaemia intermedia (BTI) is the milder form of the condition, which is also known as non-transfusion-dependent thalassaemia (NTDT).
- The symptoms of BTI will vary from person to person. Some people will experience symptoms of mild anaemia, while others will need blood transfusions.
9
Q
Sickle cell disease
A
- Abnormality of the beta globin chain (chromosome 11)
- Sixth amino acid in HbA, glutamic acid, is substituted for valine
- Newborn infant does not manifest signs of disorder until 6 months + of age when HbF should have been converted to HbA.
10
Q
Why does the RBC sickle?
A
- RBC more likely to crystallize with a low oxygen tension or pH,
- Hb molecule within, forms into a semi-gel like state
- Molecules begin to stick together creating tactoids (rod like shapes)
- Creates the sickle shape
11
Q
Sickling then leads to…
A
- Blockage of small capillaries
- Small infarcts in various parts of the body
- Painful or infarctive crisis
- These RBC usually lasts on average 7-20 days = chronic anaemia
12
Q
Sickling Crisis
A
Hypoxia damages the endothelium leading to vasoconstriction followed by vasodilation ->
There is escape of intravascular fluids leading to tissue oedema and haemaconcentration ->
-> Clotting cascade activated – thrombus in capillaries and venules ->
Emboli and infarct lead to tissue necrosis (ischaemia of bone marrow can lead to fat emboli) -> Blood viscosity and reduced blood flow lead to intravascular stasis in capillaries, terminal arteries and veins -> Available oxygen is used by vessel walls = hypoxia and further sickling -> Sickled RBCs are more readily destroyed by the reticulo-endothelial system (phagocytosis) -> Severe anaemia (Hb 6-8) and sometimes jaundice
13
Q
Sickle cell in pregnancy
A
- Woman may have her first crisis in pregnancy
- First sickle cell crisis triggered by IOL has been reported
- 1st trimester slightly reduced
- 2nd and 3rd 5 times that of a non pregnant woman
14
Q
HbSS Complications
A
- H - Haemolysis, Hand-Foot syndrome
- B - Bone Marrow Hyperplasia/Infarction
- S - Stroke: Thrombotic or haemorrhagic, Subarachnoid bleeds
- S - Skin ulcers (primarily leg)
- P - Pain episodes, Priapism, Psychosocial problems
- A - Anaemia, Aplastic crisis, Avascular necrosis
- I - Infections: CNS, Pulmonary, GU, Bone, Joints
- N -Nocturia, urinary frequency from hyposthenuria
- C - Cholelithiasis, Cardiomegaly, Congestive heart failure, Chest syndrome
- R - Retinopathy, Renal failure, Renal concentrating defects
- I - Infarction: Bone, Spleen, Central Nervous System, Muscle, Bowel, Renal
- S - Sequestration crisis involving spleen or liver
- I - Increased foetal loss during pregnancy
- S - Sepsis
15
Q
Precipatating factors
A
H – Hypoxia A – Acidosis D – Dehydration I – Infection T – Temperature changes S – Stress
