Session 5-Haemopoiesis, Erythropoiesis And Iron Flashcards
Where are RBCs, platelets and most WBCs produced?
Bone marrow
What is bone marrow aspirate?
Liquid marrow with some solid particles
What is haematopoiesis controlled by?
Hormones
Which system is responsible for the control and removal of blood cells?
Reticuloendothelial system (RES)
Which cells are part of the reticuloendothelial system?
Monocytes Macrophages Kupffer cells Tissue histiocytes Microglial cells in CNS
What are the main organs of the reticuloendothelial system?
Spleen
Liver
What do reticuloendothelial cells in the spleen do?
Dispose of blood cells
In a full blood count, what information do the following give about blood cells:
1) haemoglobin
2) red blood count
3) mean cell volume
1) how effective they are
2) how many there are
3) how large they are
What are the functions of RBCs?
1) carry Hb
2) maintain Hb in its reduced (ferrous) state
3) generate energy
4) maintain osmotic equilibrium
5) deliver oxygen to tissues
Why do RBCs have a high SA:volume ratio?
More efficient gas exchange and increases flexibility as it moves through capillaries
What can a change in the shape of a RBC result in?
Cells can become more fragile and can burst and not be functional -> anaemia
Describe the structure of haemoglobin
Tetramer of 2 pairs of globin chains each with own haem group
What are the two configurations that haemoglobin can exist as?
Oxyhaemoglobin
Deoxyhaemoglobin
Which chromosomes are the globin gene clustered on?
11 and 16
When does foetal Hb switch to adult Hb?
3-6 months of age
What is the function of Hb?
Carriage of O2 from lungs to tissues and CO2 between tissues and lungs
True or false: haem molecule combines reversibly with O2 and CO2
TRUE
What do globin chains allow?
1) protect haem molecule from oxidation
2) confer solubility
3) permits variation in oxygen affinity
What shape is an oxygen dissociation curve?
Sigmoid
Complete the sentences:
Reduced pO2 is detected in interstitial ____________ cells in kidney. This leads to increased production of ________________ hormone. This hormone stimulates maturation and release of ____ cells from marrow. Hb then rises, pO2 rises and _________________ production falls.
Peritubular
Erythropoietin
Red
Erythropoietin
What are the two main metabolic pathways in red cells?
1) glycolysis
2) pentose phosphate pathway
What are the two forms of iron?
Available (functional)
Stored
What are the functional forms of iron?
Haemoglobin
Myoglobin
Tissue iron
Transported iron
What are the types of stored iron?
Ferritin
Haemosiderin
True or false: iron requirement increases with age
FALSE - decreases with age
Which cells ‘eat’ old senescent RBCs?
Macrophages
Where is 95% of stored iron found?
Liver tissue-hepatocytes as ferritin
Where is haemosiderin found?
In Kupffer cells
True or false: humans don’t have a developed pathway for excretion of iron
TRUE
Where can haem iron be obtained from?
Meat
Where can non-haem iron be obtained from?
Pulses, nuts, grains etc
Why is haem iron a better source of iron than non-haem iron?
Iron in haem iron is present in ferrous form, which is used by us.
Non-haem iron is ferric form and this needs to be converted to ferrous form
How does non-haem iron exist?
Fe3+ (ferric)
On which surface does Fe2+ bind transferrin?
Apical surface of duodenum and upper jejunum
How is iron exported out of an enterocyte?
Ferroportin
What do foetal enterocytes have receptors for?
Lactoferrin
Iron is taken into cells by the binding of iron-transferrin complex to what?
Transferrin receptor (TfR)
Which cells contain the highest number of transferrin receptors?
Erythroid cells
Which vitamin enhances iron absorption?
Vitamin C (ascorbic acid)
What inhibits iron absorption?
Precipitation/chelation of iron eg tea, chapatis, antacids
What are the control mechanisms of iron absorption? (4)
1) regulation of transporters
2) expression of receptors
3) hepcidin and cytokines
4) crosstalk between epithelial cells and other cells like macrophages
What is hepcidin?
Negative regulator of iron absorption
Where is hepcidin:
1) secreted?
2) excreted?
1) liver
2) kidneys
When is hepcidin synthesis increased?
Iron overload
When is hepcidin production decreased?
High erythropoietic activity
What is hepcidin production regulated by? (3)
1) HFE
2) transferrin receptor
3) inflammatory cytokines
How does hepcidin inhibit iron?
Degrades ferroportin (protein involved in moving iron out of cells) and this prevents:
1) iron absorption from gut
2) iron release from macrophages
What are the reasons for iron deficiency? (2)
1) insufficient intake/poor absorption
2) increased use (pregnancy, bleeding)
What are the symptoms of anaemia?
1) tiredness
2) reduced oxygen carrying capacity (pallor, reduced exercise tolerance)
3) cardiac symptoms-angina, palpitations, development of heart failure
What are the signs of anaemia? (4)
1) pallor
2) tachycardia
3) increased respiratory rate
4) epithelial changes
True or false: iron deficiency leads to hypochromic and microcytic cells
TRUE
What is the most commonly used measure of iron status?
Ferritin (acute phase protein)
When is CHR used to test for iron deficiency?
If a patient has an infection
What are the possible treatments of iron deficiency? (5)
1) dietary advice
2) oral iron supplements (with orange juice)
3) intramuscular iron injections
4) intravenous iron
5) transfusion (not unless there is severe anaemia)
What can reduced iron produce?
Highly reactive hydroxyl and lipid radicals
What is excess iron deposited as in tissues?
Haemosiderin
What is haemochromatosis?
Disorder of iron excess resulting in end organ damage due to iron deposition
What does haemochromatosis cause?
Liver cirrhosis Diabetes mellitus Hypogonadism Cardiomyopathy Arthropathy Skin pigmentation
True or false: hereditary haemochromatosis is autosomal dominant
FALSE - recessive
What is hereditary haemochromatosis a mutation in?
HFE gene
What does HFE protein usually do?
Competes with transferrin for binding to transferrin receptor
What happens to HFE in hereditary haemochromatosis?
Mutated HFE cannot bind so transferrin has no competition, too much iron enters cells
How is hereditary haemochromatosis treated?
With venesection
What is used to treat transfusion associated haemosiderosis?
Iron chelating agents
