Haemopoiesis, Erythropoiesis and Iron Flashcards
Where are blood cells produced?
Bone marrow
What are the three main types of blood cells?
RBC, platelets and WBC
Where are the main sites of haemopoiesis in the adult?
Pelvis, sternum, skull, ribs, vertebrae
Where is a bone marrow trephine usually taken from?
Posterior iliac crest
What are the common myeloid progenitors able to differentiate into?
Erythrocytes, monocytes, basophils, neutrophil, eosinophils, platelets
What are the common lymphoid progenitors able to differentiate into?
T and B lymphocytes, NK cells
What is haemopoiesis driven by?
Cytokines
How is the pool of stem cells not depleted?
When they proliferate, at least some of their daughter cells remain as HSCs
What are the 3 blood cell lineages?
Erythroids (reticulocytes and erythrocytes)
Lymphocytes
Myelocytes (macrophages, granulocytes and megokaryocytes)
What do megokaryocytes give rise to?
Platelets
For example, if we wanted a stem cell to develop into more erythocytes, what growth factor would be given?
Erythropoietin
For example, if we wanted a stem cell to develop into more platelets, what growth factor would be given?
Thrombopoietin
For example, if we wanted a stem cell to develop into more granulocytes, what growth factor would be given?
G-CSF
What are some examples of cells contained within the reticuloendothelial system?
Monocytes Macrophages Kupffer cells Tissue histiocytes Microglial cells in CNS
What is the normal haemoglobin range for an adult male?
130-180 g/L
What is the normal haemoglobin range for an adult female?
115-165 g/L
What is the normal red blood count range for an adult male?
4.5-6.5 x 10^12 /L
What is the normal red blood count range for an adult female?
3.9-5.6 x 10^12 /L
What is the normal mean cell volume range?
80-100 fL
What is the normal white blood count range?
4-11 x 10^9/L
What is the normal platelet count range?
150-400 x 10^9 /L
What are the functions of the RBC?
1) Carry haemoglobin
2) Maintain haemoglobin in its reduced (ferrous) state
3) Generate energy (ATP)
4) Maintain osmotic equilibrium
How long does a red cell usually last for?
Around 120 days
Why is the RBC so flexible?
Membrane proteins
Why does the RBC need to be so flexible?
To facilitate passage through the microcirculation which has a minimum diameter of 3.5 micrometres (diameter of RBC = 8 micrometres)
What chemical is seen in increased levels in the blood if red cells are being destroyed more rapidly than usual?
Bilirubin
Where is bilirubin excreted?
Bile and urine
What are the two main metabolic pathways in red cells?
Glycolysis and pentose phosphate pathway
Which organ detects reduced oxygen in circulation?
Kidneys
What would happen to haemoglobin levels in a patient with kidney failure?
Decreases (anaemic) as erythropoitein not being released properly
True or False:
There are many mechanisms within the body that function to excrete iron
False
No mechanism of excreting iron
In what ways can iron be present in the body?
In haemoglobin, myoglobin, tissue iron, transported iron
Ferritin, haemosiderin
Is ferratin soluble?
Yes
Is haemosiderin soluble?
No
How much iron enters and leaves the body each day?
1-2mg
What are the two forms of iron we can obtain through our diet?
Haem (eg in meat)
Non-haem (eg in nuts, grains)
Why is haem iron a better source than non-haem iron?
Enters enterocyte and iron released as Fe2+ - ferrous
As opposed to non-haem - exists in the ferric (Fe3+) form and is reduced to ferrous iron before being transported across the intestinal epithelial
What form must iron be in to be absorbed?
Ferrous (Fe+)
What can happen to iron after it is absorbed into the intestinal lining cells?
Can either be stored as ferritin or absorbed into the blood
What is iron exported out of the cell by?
Ferroportin
How is iron taken into red blood cells?
By binding of iron-transferrin complex to transferrin receptor
Which cells contain the highest numbers of transferrin receptors?
Erthyroid cells
What vitamin enhances absorption of iron?
Vitamin C
What things can inhibit the absorption of iron?
Tea, chapatis, antacids
What things control iron absorption?
Regulation of transporters
Expression of receptors (eg transferrin receptor)
Hepcidin and cytokines
Crosstalk between epithelial cells and other cells like macrophages
Where are dietary iron levels sensed?
Villi of enterocytes
What is hepcidin?
Protein that regulates iron absorption
How does hepcidin work?
Hepcidin inhibits iron transport by binding to ferroportin which is located on the basolateral surface of gut enterocytes and the plasma membrane of reticuloendothelial cells (macrophages).
What is hepcidin secreted and excreted by?
Secreted by liver, excreted by kidneys
When is hepcidin synthesis increased?
In iron overload
What happens to the production of hepcidin when there is high erythopoietic activity?
Production is decreased
What are the functions of hepcidin?
Prevents iron release from macrophages and prevents iron absorption from gut
What are some symptoms of iron-deficiency anaemia?
Tiredness, reduced exercise tolerance, angina, palpitations
What are some signs of iron-deficiency anaemia?
Pallor, tachycardia, increased respiratory rate, epithelial changes
What are some features of red blood cells in iron-deficiency anaemia?
Hypochromic (low Hb content)
Microcytic (small RBC-low MCV)
Change in size and shape (eg pencil cells)
What is the most commonly used measure of iron levels?
Serum ferratin
What do reduced ferratin levels indicate?
Iron deficiency
Do normal or increased levels of ferratin definitely exclude iron deficiency?
No
Why is excess iron so dangerous?
- Exceed binding capacity of transferrin
- Reduced Fe (Fe2+) can produce highly reactive hydroxyl and lipid radicals
- Damage lipid membranes, nucleic acids and proteins
- Excess iron deposited in tissues
What is haemochromatosis?
Disorder of iron excess resulting in end organ damage due to iron deposition
What can haemochromatosis cause?
Liver cirrhosis, diabetes mellitus, hypogonadism, cardiomyopathy, arthropathy and skin pigmentation
How is hereditary haemochromatosis inherited?
Autosomal recessive
What is hereditary haemochromatosis caused by?
Mutation in gene designated HFE on chromosome 6p21.3
Normally HFE protein competes with transferrin for binding to the transferrin receptor
Mutated HFE cannot bind so transferrin has no competition, meaning too much iron enters cells
How is hereditary haemochromatosis treated?
Venesection
