Physiology 4 Flashcards
(45 cards)
Outline the pathophysiology of the thalassaemias
Heterogeneous group of genetic disorders which affect rate of globin gene expression.
α-thalassaemias usually involve gene deletion
β-thalassaemias usually involve abnormal processing
How many functioning α and β genes are present in the erythroid precursor?
4x α and 2x β due to replication of the α gene
What are the α-thalassaemia traits?
α0 trait: Loss of both α genes from one chromosome (α0 α0 / α+ α+)
α+ trait: Loss of one α gene on one chromosome (α+ α0 / α+ α+)
homozygous α+ trait: Loss of one α gene on each chromosome (α+ α0 / α+ α0)
What clinical picture do the α-thalassaemia traits produce?
Similar
Usually not anaemic
Hypochromic, microcytic RBCs, raised RBC count
Hb electropheresis normal, HbA2 level normal
What is HbH disease?
3x α gene deletions Causes anaemia (Hb 70-110) Microcytic, hypochromic RBCs. Splenomegaly HbH can be detected byh electropheresis
What happens if all four α globin chain genes are lost?
Hydrops foetalis
Death in utero
What causes β-thalassaemia?
DNA mutation resulting in absent (β0) or reduced (β+) β globin production.
How does β-thalassaemia major present?
As severe, transfusion-dependent anaemia (hpyochromic, microcytic) with onset around 3-6 months.
This is the time when the switch from γ to β globin takes place.
Serum electropheresis reveals reduced or absent HbA
Complications of β-thalassaemia?
If untreated by transfusion:
Bone marrow hyperplasia in skull and other haematopoeitic areas. Cortical thinning leading to fractures.
Hepatosplenomegaly
‘Hair on end’ appearance of skull x-ray
With transfusion: Iron overload after first decade.
What storage solution is used for red cells in Europe?
SAG-M Saline Adenine Glucose Mannitol
Explain why each component of SAG-M storage solution is included
Saline: solvent and osmotic agent
Adenine: Increases intracellular ATP levels, prolonging RBC survival (though at the cost of decreased 2,3-DPG levels)
Glucose: Prolongs cell life
Mannitol: Osmotic stabiliser reducing storage-related haemolysis
How are packed red cells presented?
150-200ml concentrated RBC solution suspended in 100ml storage solution.
Single donor.
Haematocrit 50-70%
What is the shelf-life of packed RBCs?
35 days at 2-6°C (if adenine-containing solution used)
How are platelets presented?
Units of 250-300ml
Combined pool of several donors
What is the shelf life of pooled platelets?
3 days at 22°C
Risk of bacterial proliferation beyond this
Storage below 18°C damages platelet function
How is fresh frozen plasma presented?
Units of 200-300ml
Single donor
Rapidly frozen to -25°C after donation
Once thawed must be used within 6h
What is the shelf life of FFP?
1 year at -25°C
How is ABO group inherited?
Mendelian dominant inheritance
What is an agglutinin?
An antibody to ABO antigens
How are ABO antigens created?
All have a common precursor - the H antigen
H-gene codes for fructose transferase which adds fructsose to end of the H oligosaccharide
Addition of a terminal sugar defines the ABO type of the antigen
Group A antigens have an N-acetyl galactosamine added to the H antigen
Group B antigens have a galactose molecule added to the H-antigen
Where are ABO antigens found in the body?
Many tissues (including surface of erythrocytes)
Where are Rhesus antigens found in the body?
Only on the surface of erythrocytes
What is the most antigenic Rhesus antigen?
Rhesus D
How prevalent is the Rhesus D antigen?
85% of caucasians +ve
99% of Asians +ve
