Haematology 4 (haemoglobin Molecule and Thalessemia) Flashcards
Describe the synthesis of haem?
And where is it synthesised in?
- combination of protoporphyrin ring with central iron atom (ferroprotoporphyrin)
- synthesised mainly in mitochondria which contains enzyme ALAS
Each gram of Hb contains _______ of iron
3.4 mg
When does hb synthesis occur?
Hb synthesis occurs during development of RBC and begins in pro-erythroblast:
- 65% at erythroblastosis stage
- 35% at reticulocyte stage
List clinical presentation of thalessaemia major?
- severe anaemia (after 4 months)
- hepatosplenomegaly
- blood film shows gross hypochromia, poliokilocytosis + many NRBCs
- bone marrow
- extra medullary haematopoiesis
Describe the gene clusters on
Chromosome 16 + Chromosome 11
Chromosome 16
- contains 2 alpha genes
- an embryonic gene
- some pseudo genes
- genes = all next to each other in a cluster
Chromosome 11
- contains beta genes
- delta genes
- gamma genes
- genes = all next to each other in a cluster
- these genes = all arranged in their clusters in the order that they are expressed
Describe the structure of hb, and where it is synthesised in ?
Haem - synthesised in mitochondria
Globin - synthesised in ribosomes
How would you monitor iron overload?
- serum ferritin
- liver biopsy
- cardiac and hepatic MRI
- ferriscan (R2 MRI)
Describe the shape of the oxygen- hb dissociation curve
Sigmoid shape
- due to cooperativity
- p50 = 26.6mmhg
What 4 factors affect the normal position of the hb-oxygen dissociation curve?
- conc of 2,3 - DPG
- H+ ion conc (PH)
- CO2 in rbc
- structure of hb
What may cause hb-oxygen dissociation curves to shift to the left?
- Low 2,3 - DPG
- HbF
Describe the 2 methods by which thalassaemia is classified by?
Classified by=
- Globin type affected
- Clinical severity (minor, intermedia, major)
Approximately how much hb is produced and destroyed in the body everyday?
90 mg/kg
What is is the mechanism of beta thalassaemia?
- deletion or mutation in beta globin genes
- reduced/ absent production of beta globin chains
- beta thalassaemia major = diagnosed + treated in early infancy
What is the inheritance pattern of beta thalassaemia?
- recessive Mendelian
- carriers = asymptomatic
List clinical features of beta thalessaemia?
- chronic fatigue
- failure to thrive
- jaundice
- delay in growth + puberty
- skeletal deformity
- splenomegaly
- iron overload
- -> cardiac failure
What is a main feature of thalassaemia?
- microcytic hypochromic blood picture
- in absence of iron deficiency
- rbc count is relatively high (compared to hb)
- increase in central pallor
- increase in teardrop shaped cells
what is beta thalassaemia usually caused by?
- point mutations
What are traits of beta thalessaemia?
- hb may be normal
- Low MCV
- LOW MCH
- Increased RBC count
- HBA2 = increased (doesn’t occur in alpha thalessaemia)
What factors cause hb-oxygen dissociation curve to shift to the right ?
- high 2,3 - DPG
- high H+
- high CO2
- HbS
Describe thalessaemia major
- what is a main symptom?
- clinical presentation = ______
- 2 abnormal copies of beta globin gene
- severe anaemia (need regular blood transfusions)
- hepatosplenomegaly
- blood film = hypochromia + poikilocytosis
- bone marrow
- clinical presentation = after 4-6 months of life
There are __ functional globin chains.
Arranged in 2 clusters ___ and ____
There are 8 functional globin chains.
Arranged in 2 clusters alpha and beta
What extra molecule do you have in tight configuration?
And what is it’s function?
2,3 - DPG
Function:
- forms extra bonds which makes the molecule less flexible
- as more O2 binds, hb molecule switches from tight form —-> relaxed form (so can accommodate more oxygens)
- OVERALL: facilitates o2 delivery to tissues
In beta thalessaemia major what are the 2 forms of inclusion bodies ?
- alpha globin precipitates
- pappnheimer bodies
What is a Thalessaemia carrier
- aka thalessaemia minor / trait
- carry 1 abnormal copy of beta globin gene
- usually asymptomatic
- mild anaemia
