Flashcards in Pathology L06 Red blood cells Deck (30)
What are RBCs unable to do since they lack mitochondria and ribosomes?
incapable of both oxidative phosphorylation and protein synthesis
What is the diameter or a RBC?
What are 3 functions of Hb?
Oxygen transport (main), carbon dioxide transport (10% of CO2 from tissue to lungs) and NO transport
What chromosome are the alpha and beta globin genes found on?
16 and 11 respectively
What is haemoglobin switching?
The sequential expression of embryonic, fetal and adult haemoglobin in the developing erythroblast during ontogeny
What makes O2 binding to Hb co-operative?
Binding of each oxygen enhances binding of the next - Bohr effect
What 3 changes can cause a lower O2 affinity?
reduced pH, increased temp and increased 2,3 BPG
What is the advantage of HbF not being able to bind 2,3 BPG effectively?
HbF has a higher affinity than HbA for oxygen. Oxygen is preferentially loaded onto HbF in fetal blood from HbA in the mother's blood
What are the 2 pathways for glucose metabolism in the RBC?
Glycolysis and Hexose monophosphate shunt (pentose phosphate pathway)
What is the purpose of the reducing power generated by the HMP shunt?
Countering any potential reactive oxygen species that may form from the oxygen carried (OH-, H2O2, HO2, O2-) and the damage to lipids, proteins and enzyme cofactors they would produce. It does this by producing NADP/H and Glutathione
What is methaemoglobin?
An oxidise form of Hb with Fe3+ instead of Fe2+. It cannot carry oxygen and precipitates out.
What is the enzyme converting glucose 6P to 6P gluconate?
glucose 6P dehydrogenase
How does HMP shunt prevent oxidative stress?
Production of large amounts of NADPH that prevents oxidative stress by maintaining glutathione levels. Glutathione is a reducing agent that converts peroxide to water and prevents oxidative damage.
In patients with G6PD deficiency, what oxidising agents may trigger oxidative stress?
medications, broadbeans and infections
What might the anaemia from pyruvate kinase deficiency (most common glycolytic enzyme deficiency) not be as symptomatic as expected?
PK def causes loss of membrane pump function and loss of membrane plasticity, leading to usually shaped cells that are destroyed in the spleen. There is also an increase in 2,3-DPG, shifting the haemoglobin curve to the right, allowing greater offloading of oxygen. As a result, only appear slightly anaemic.
What are the 2 crucial structural aspects of the red cell membrane?
1. Must have a lot of it - high SA to volume ratio
2. Must have an effective supporting scaffold/cytoskeleton to prevent membrane loss during day-to-day wear and tear
What red cell membranopathy does defects in vertical interactions lead to?
Hereditary spherocytosis, as there is a membrane loss causing low SA:V
What red cell membranopathy does defects in horizontal interactions lead to?
Of all red cell antigens, which system is the most immunogenic?
What is Landsteiner's rule?
Individuals lacking A or B from RBCs will have the corresponding antibody in their plasma - mix of IgM and IgG antibodies
What is the time course for ABO antibody production, detection?
Production begins after birth, detected by 4-6 months of age and peaks at 5-10 years
What is the impact of ABO mismatch?
Large scale, rapid destruction of transfused red cells. IgM antibodies activate the complement cascade - 9 plasma proteins. End result is a hole (due to MAC) punched into the donor cells resulting in red cell destruction.
Antibodies for the Rh system are 'naturally formed'. True or false?
When are Rh antibodies formed?
Formed upon exposure of negative individuals to Rh positive blood: transfusion or pregnancy (fetus is RhD positive and mother is RhD negative)
What produces 2,3-DPG?
Glycolysis in RBCs
What is 'band 3' and what does it do?
Band 3 is the most abundant protein in the RBC cell membrane. It is an anion exchanger (Cl-/HCO3-), and is linked to the cytoskeleton for structural integrity. It also has over half of the ABO antigens attached to it
How many major phospholipids are in the RBC membrane? Which enzymes maintain the lipid bilayer of the RBC membrane?
- 5 major phospholipids
- Floppases, Flippases and Scramblases
What are the ABO antigens?
A, B, A.B
What are the Rh antigens, and which is the most immunogenic?
-D, C, c, E, e. Over 50 in reality
-D is the most immunogenic