End of week formative 1 Flashcards
The normal RBC has a smooth biconcave shape - what are the functional implications of this shape?
Surface area maximised for absorption and release of oxygen and carbon dioxide
Flexibility (can be reversibly deformed) to allow passage through all the smallest capillaries
The nucleus is lost before leaving the bone marrow. This has consequences for the cell. How does the red cell get into the blood?
Erythropoeitin stimulates maturation of red cells which then pass into the blood by squeezing through gaps in the vascular epithelium
Enucleation results in reticulocyte being formed and involves macrophage taking up the nucleus (pyrenocyte)
In what circumstance might nucleated red cells appear in the blood?
If bone marrow is stressed (cells leave more quickly)
Physical damage - if endothelial problem (nucleated red cell is more immature than an erythrocyte - would get removed in spleen etc. so they don’t last long in the bloodstream)
Also seen in newborn, malignancy, haemorrhage, hypoxia, red cell destruction, drowning
What are consequences of having no nucleus in RBCs?
No DNA -> no DNA synthesis (cell life of about 120 days)
For a day or two, the new RBCs look a bit more blue than older ones on blood film. Why?
The more immature cells have some RNA in them still
The cellular contents are packed full of haemoglobin molecules. These are best when they are bright red. Why do haemoglobin molecules change colour?
Oxygenated haemoglobin is brighter red than deoxygenated (D orbitals in transition metals)
Each haemoglobin molecule contains four “chains”, each made up of three parts: a globin chain, a protoporphyrin ring and iron. Explain how each part of haemoglobin contributes to the function of a RBC
Primary function of red cell is to bind oxygen in lungs and release it in tissues. Oxygen binds to iron in the form of Fe2+ contained in haem - the protoporphyrin ring of haem helps stabilise the ferrous form of iron, though it can be oxidised (reversibly) to methaemoglobin (free iron would be toxic)
The protein part allows for conformational changes which are dependent on pH and oxygenated state, and alter the affinity of the molecule for oxygen in such a way that it binds and releases oxygen in physiologically appropriate conditions
Why does the haemoglobin molecule need to be in a RBC?
Viscosity - such a quantity of protein in solution would be quite viscous and would not flow easily
Stability - Hb would be broken down if not within RBCs and excreted by kidney - would damage kidney -> disseminated intravascular coagulation etc. (this does happen in intravascular haemolysis)
Think of a spherocytic red blood cell whose membrane has been damaged. Its membrane is tight and the biconcave shape has been lost. However, it can manage to struggle through most blood vessels and it has the same content of haemoglobin as normal red blood cells. Explain the different mechanisms by which the red cell membrane can be damaged
Defects may be inherited or acquired (some drugs are toxic to the membrane; sepsis; complement in antibody reaction; oxidative stress)
The defective component in the membrane gets damaged as it goes through the spleen
What is a reticulocyte?
An early red cell with some RNA still in it
What is the significance of reticulocytes in the bloodstream?
Shows that the bone marrow is still producing cells, therefore the problem is not productive, but rather a destructive problem
Think of a spherocytic red blood cell whose membrane has been damaged. Its membrane is tight and it has lost its biconcave shape. However, it can manage to struggle through most blood vessels and it has same content of haemoglobin as normal red blood cells.
The patient is not anaemic despite these problems with the cell membrane. Why should this be?
Although destruction is occurring, production is keeping up - i.e. compensated haemolysis (or compensated blood loss)
Think of a spherocytic red blood cell whose membrane has been damaged. Its membrane is tight and it has lost its biconcave shape. However, it can manage to struggle through most blood vessels and it has same content of haemoglobin as normal red blood cells.
When would anaemia occur?
If bone marrow can’t keep up, then destruction exceeds production; bone marrow can’t exceed 6x normal level; or it may not be functioning properly due to lack of folate, or certain viral infections
In station 1 you met the normal red blood cell and learnt of its evolution into a finely tuned O2 transport system, but for this exquisitely regulated system there is a cost. Every cell in your body is exposed to free radicals and oxidative damage every day.
Why are red blood cells more vulnerable to oxidative damage?
They contain Fe2+, and a number of reducing systems; but they have no protein making system to replace damaged proteins
b) What are the sources of energy and reducing powers which protect the red blood cell against oxidative damage?
Red cells get their energy by glycolysis (anaerobic); the reducing systems are NADPH hexose shunt G6PD dependent (and NADH)
Consider a red blood cell with markedly reduced protection from oxidative damage.
c) Describe how this could have arisen?
Enzyme deficiency (G6PD): an x-linked condition mainly affecting boys - partial defect?
Oxidative stress - some drugs can accelerate damage
The body is very vulnerable taking drugs that can induce oxidative stress such as dapsone
d)What would be the potential clinical manifestations of this?
Dapsone can cause red cell damage, and intravascular haemolysis
Here is a common problem with red blood
cells. They can be seen on a blood film as
small and stiff. They do not manage through
the capillaries very well. They all look pale
and pasty and have so few haemoglobin
molecules.
a) Why are they smaller than a normal red
blood cell?
Haemoglobin concentration dictates when cell division stops;
They don’t have enough haemoglobin molecules. Cell division occurs normally and anaemia = high epo stimulates division
The Hypochromic Microcytic Red Blood Cell
Here is a common problem with red blood cells. They can be seen on a blood film as small and stiff. They do not manage through the capillaries very well. They all look pale and pasty and have so few haemoglobin molecules.
b)Why might this be?
The cells are deficient in Hb perhaps because not enough iron, or problem with either protoporphyrin or globin production; in thalassaemia - imbalance of alpha and beta chains leading to intramedullary haemolysis too
c) What is going to happen to the patient as a consequence of failure of haemoglobin synthesis?
Pale, tired, SOB (anaemic)
Stress on systems requiring oxygen (muscles) and heart. Tachycardia increase cardiac output
How might the red cell try and improve oxygen delivery?
Shift oxygen dissociation curve (produce 2,3-DPH) Rappaport Lumbering shunt
Case 1
Hypochromic Microcytic Red Blood Cell
It is difficult to make haemoglobin if there is a deficiency of β-globin chains.
Every red blood cell in this patient has this problem and it’s been that way since birth
a) Why do I have this difficulty?
Genetic beta thalassaemia
Hypochromic Microcytic Red Blood Cell
It is difficult to make haemoglobin if there is a deficiency of β-globin chains.
Every red blood cell in this patient has this problem and it’s been that way since birth
How does it affect the patient?
Failure to make HbA (a2b2)
Severity of anaemia depends in beta thalassaemia, depends on whether homo- or heteroxygous
Major (homozygous) severe aenamia but in the trait (heterozygous) compensation mechanism are sufficient - however screening could be important if pregnant.
Iron should not be given for this anaemia, it is not needed
Hypochromic Microcytic Red Blood Cell
The reason for inability to synthesise haemoglobin is that there isn’t enough iron.
a) Why might this problem happen?
Heavy menstrual loss
Malabsorption
Dietary deficiency
Chronic GI blood loss
These red cells are from a patient who, unlike in Case 1, can do something about his problem
Hypochromic Microcytic Red Blood Cell
The reason for inability to synthesise haemoglobin is that there isn’t enough iron.
b) What questions should you ask the patient?
Investigate the cause (questions and investigations relevant to menstrual loss, diet, GI blood loss, colour stools)
Diet review
Features of malabsorption
Station 4 The Macrocytic Red Blood Cell
This macrocytic red blood cell is in a patient who has megaloblastic anaemia due to cobalamin (Vit.B12) deficiency.
a) What is the effect of B12 deficiency on all the cells of the body?
Vit B12 is involved in thymidine synthesis from uracil and therefore DNA synthesis; cell division is impaired
The intensive production of cells in bone marrow means it is one of the first to show the effect of this deficiency; the cells are bigger because there are fewer mitoses en route to maturation - ineffective erythropoeisis as some failing precursors undergo apoptosis
What do lanes 1 to 4 represent as conditions?
What is this?
Describe the offspring of two people with thalassaemia trait
