7. Haemoglobin & Sickle Cell Anaemia Flashcards
haemoglobin facts
average adult contains 5000 million rbcs per ml of blood
each rbc has 280 mill Hb
average adult has 5L blood
haemoglobin structure
comprised of 4 chains - two alpha and two beta
cooperation between globin chains optimises the oxygen delivery profile
genetics of haemoglobin
beta globin gene is produced from chromosome 11
alpha globin gene is on chromosome 16
on the chromosome 11 we have:
-epsilon globin gene produced during embryonic development
-gamma globin gene takes over during fetal growth where HbF is produced
-delta
-beta globin
on chromosome 16 it is 2 zeta and 2 alpha, we inherit one beta globin gene from each parent and two alpha globin genes from each parent so total of 4 alpha globins
haemoglobin development
genetic defects of haemoglobin are the most common genetics defects in the world
different genes are activated or suppressed depending on the stage of development
normal adult haemoglobins
less than 1 % of HbF in adults chromosome 11
haemoglobin A
- normal haemoglobin that exists after birth
- a tetramer with two alpha chains and two beta chains α2β2
haemoglobin A2
a minor component of the haemoglobin found in red cells after birth
consists of 2 alpha chains and 2 delta chains α2δ2
less than 3% of the total red cell haemoglobin
haemoglobin F
predominant haemoglobin during fetal development
a tetramer of two alpha chains and two gamma chains α2γ2
haemoglobin in circulation
at the peripheral tissues there is a low (acidic) pH so a high pCO2 and a low pO2. mainly deoxyhaemoglobin present here as oxygen needs to be given up to respiring tissues
in the lungs there is a high pH and a low conc of pCO2, high pO2. this is where we have oxyhaemoglobin subunit as oxygen taken up
thalassaemias and haemoglobinopathies
disorders affecting haemoglobin synthesis or function leading to anaemia as rbc shape deformed and recognised as dysfunctional so broken down prematurely
thalassaemia: decreased synthesis of wild type haemoglobin, normal globin structure. quantitative
haemoglobinopathies: synthesis of mutant haemoglobin chains (eg sickle cell anaemia). qualitative (quality of hb is affected
classification not straightforward: some abnormal globins are synthesised at a reduced rate
sickle cell anaemia
a haemoglobinopathy
incidence: West African, Afro- carribean have higher incidences
when the sickle haemoglobin loses its oxygen (deoxy state) it forms long rods in the red cell and changes its shape) so not biconcave disc
inheritance of sickle cell anaemia
if you only inherit one sickle cell gene from one parent u can pass it on but not suffer any symptoms, - sickle cell trait (heterozygous) carrier
sickle cell disease - red blood cells inherit 80% HbS, you will have inherited one gene from each parent
sickle cell anaemia - biochemical analysis
abnormal haemoglobin structure , Pauling discovered the allelic change occurs in a single gene. first demonstration that a genetic mutation can produce a physically different protein
- caused by point mutation in the beta globin gene from A to T so changes to valine
this had a dramatic effect on the haemoglobin tetramer in the deoxy state, hb wants to lose its oxygen
sickle cells in circulation
HbS is insoluble and forms crystal when it is exposed to low oxygen tension (pressure)
deoxygenated sickle haemoglobin polymerises into long fibres
will take up O2 in the lungs but will give it up as it travels thorugh the body, but forms crystals as lower pO2 towards tissues and hb cant revert back to oxygenated form, gradual process
pathophysiology of sickle cell anaemia
deoxygenation to the polymerisation of Hb to the sickling of rbc toendothelial activation/ damage which means blood cant flow freely through vessels. activation triggers clotting/ can cause damage as elements are exposed to things in circulation like rbc wbc and these will stick to blood vessel lining ie the endothelium. neutrophils can release things and cause further damage
sickle cells get stuck in blood vessels and cause vascular occlusion, liits blood flow so less to organs. oxygen ischaemia and organ damage
complications from sickle cell disease
sickle cells become trapped and destroyed in the spleen causing splenic sequestration
- shortage of red blood cells or anaemia
- pain episodes
- stroke or brain damage
kidney failure
- pneumonia or chest syndrome (respiratory, occlusions in pulmonary vasculature)
- chronic damage to liver
- osteomyelitis, reduced blood supply to bones
sickle cell anaemia - crises
vasoocclusive
-most common
-sickle cells adhere to neutrophils and endothelial cells
-can affect the bones, lungs, spleen, brain and spinal cord
visceral
-sickling within organ occurs and pooling of blood
-can make the anaemia worse
haemolytic
-increase rate of haemolysis (destruction of rbc due to abnormal shape)
-fall in haemoglobin
sickle cell anaemia diagnosis
Low haemoglobin (6-9 g/dL)
Sickle cells and target cells in blood
Blood is deoxygenated and tests for sickling are positive
Electrophoresis – no HbA is detected, HbF levels vary between 5-15% (when we see HbF conc rising we can see sickle cell anaemia)
