Red Blood Cells Flashcards
Describe 5 important features of red blood cells, the functional relevance of each and limitations.
Full of haemoglobin
- Carry oxygen
- High oncotic pressure, oxidation risk
No nucleus
- Deformable, more room for Hb
- Can’t divide or replace damaged proteins (limited lifespan)
No mitochondria
- Limited to glycolysis for energy generation
High surface area/ volume
- Allow for gas exchange
- Need specific ion concentrations to keep water out
Flexible
- Can squeeze through capillaries
- Specialised, protein membrane required
Describe the relevance & implications of the proteins in a RBC membrane
The specialised RBC membrane contains peripheral and integral proteins that make it more flexible.
If a gene that codes for one of these protein was to become mutated it could affect the flexibility & limit the survival of RBCs
What is the relevance of the NA/K pumps in RBCs
The Na/K pumps maintain the correct ion concentrations to keep water out of the RBC. This needs energy/ ATP!!
Describe haemoglobin structure
A tetrameric globular protein
HbA(Adult) has 2 alpha and 2 beta globulin chains
Heme group is Fe2+ in a flat porphyrin ring
One heme per subgroup
Name the three main functions of haemoglobin
Deliver oxygen to the tissues
Act as a buffer for H+
CO2 transport
What Fe charge can oxygen bind to
Fe2+ NOT Fe3+
What is erythropoiesis? Outline the steps.
Erythropoiesis - The production of RBCs in the bone marrow as a result of proliferation & differntiation of HSCs.
Outline of steps - HSCs => MPP => CMP => MEP => Reticulocytes => Mature erythrocyte
Note - The maturation from reticulocytes to mature erythrocytes occurs in the blood.
The key step(s) - The formation of mature erythrocytes from MEP. The MEP cells proliferate and differentiate, increasing their amount of Hb, losing their nucleus and decreasing in size.
How are RBCs produced and where in the body does this happen?
- Proliferation & differentiation of HSCs
- In the bone marrow
How is erthyropoiesis regulated
By erythropoietin
Secreted by Kidneys
In response to hypoxia
Detected by oxygen sensing cells in kidneys
What is a RBCs average life span
120 days
How and where are RBCs destroyed
- In the spleen (& liver)
- By macrophages
Red cell contents are recycled. State the fate of the globin chains & heme group.
- Globulin chain is recycled to AAs
- Heme broken down into Fe & bilirubin i.e.
- Fe2+ recycled
- Porphyrin ring broken down into bilirubin
What happens to the bilirubin produced in the spleen?
Bilirubin taken to liver and conjugated
Then excreted in bile (colours faeces and urine)
The large amounts of oxygen in RBCs mean that oxygen free radicals are easily generated. Why is this dangerous?
Free radicals can oxide Fe2+ to Fe3+ &
Fe3+ can’t transport O2.
Free radicals also damage proteins &
Since RBCs have no nucleus, proteins can’t be repaired/ replaced
What important molecule produced in glycolysis prevents the oxidation of Fe2+ to Fe3+
Glutathione (GSH)
What is metHb
Hb group with a Fe3+ group instead of Fe2+
MetHb therefore cannot carry oxygen
Superoxide & hydrogen peroxide are free radicals (unpaired free electrons). What molecule reacts with hydrogen peroxide to remove it? What reaction occurs? What is the product?
Glutathione (GSH)
Reduction of hydrogen peroxide
Produce water & oxidised glutathione product (GSSG)
How is glutathione replenished? What is the rate limiting enzyme in this process? What is the medical implications of this?
By NADPH which is generated in the hexose monophosphate shunt.
Rate limiting enzyme - Glucose-6-phosphate dehydrogenase (GP6D).
Medical implications - Gene that makes GP6D is X-linked which is a problem if a male has a mutation in the gene.
Describe the difference in haemoglobin structure in foetus
Two alpha, two gamma subunits
How many oxygen molecules can Hb, and therefore a single RBC, hold?
4 O2 molecules per Hb
16 O2 molecules per RBC
What shape is the dissociative curve of haemoglobin and why is this?
Sigmoidal curve
- As first oxygen binds to a haem in one subunit the Hb shape changes
- This alters how easy it is for the next O2 to bind to the haem in the next subunit (Allosteric/ cooperative binding)
Compare the oxygen dissociation curves of foetal Hb, Hb & myoglobin
Myoglobin & Foetal Hb - Have dissociation curves further to the left than adult Hb meaning they can take oxygen from RBCs
Name 3 molecules and one other factor that can move the oxygen dissociation curve of Hb to the right. Explain how they achieve this and the relevance.
Low pH (high CO2 & H+), High 2,3-DPG concentrations & High temperature
When they bind to Hb they alter its structure & decrease its affinity for O2.
This causes the dissociation curve to shift to the right meaning RBC O2 saturation is less at the same pO2 pressure.
These conditions occur at tissues, allowing more oxygen to be released.
Majority of CO2 is transported from tissues to the lungs as bicarbonate. Describe the role of RBCs in this
RBCs take up CO2 at tissues
CO2 reacts with water in RBCs to produce HCO3- & H+
HCO3- then moves into the blood via the Cl/HCO3 exchange
At the lungs this processes is reversed to produce CO2 for expiration
NOTE - Deoxygenated Hb plays an important role in buffering the H+ produced
High 2,3-DPG levels cause the release of oxygen from Hb. What is the name of the pathway that produces 2,3-DPG from an intermediate product in glycolysis.
Rapapport-lubering shunt
What molecule & pathway is involved in reversing MetHb formation i.e. reducing Fe3+ to Fe2+
NADH reduces Fe3+
NADH is generated by the Eden-Myerhoff pathway
