Haemopoiesis, Iron Flashcards
Where does haemopoiesis occur ?
Bone marrow
Throughout skeleton in infant
Centrally located in adult (perlvis,sternum,skull,ribs…)
Where do we take trephine biopsy from ?
Left posterior iliac crest
What is the origin of haematopoietic cells ?
Multipotent haematopoietic stem cell
aka Haemocytoblast
What are the precursors of the haemopoietic cell lines ? which cells do they give ?
- Common myeloid progenitor , gives Erythrocyte, Megakaryocyte,Myeloblast (Granulocytes)
- Common lymphoid progenitor , gives LB and LT
Which hormone stimulate the production of RBC; Platelets,granulocytes and lymphocytes ?
- RBC : EPO
- Platelets : Thrombopoietin
- Granulocytes : GM-CSF
- Lymphocytes : IL , TNFs
What is the RES ? function ?
Reticuloendothelial system
A network in blood and tissues which is part of the immune system containing phagocytic cells
Role is to control and remove damaged/old blood cells
What are the main organs of the RES ?
Spleen , liver
Which cells are part of the RES ?
Scavenger cells :
macrophage/monocyte/Kupffer cells / histiocytes/Microglial cells in CNS
Normal range of haemoglobin ?
130-180 g/L
Normal RBC count ?
4.5-6.5 x10^12 /L
Normal Mean Cell Volume ?
80-100 fL
Normal WBC count ?
4-11 x10^9 /L
Platelet count ?
150-400 x 10^9 / L
When does the switch from foetal to adult haemoglobin occur ?
3-6 months old
In which state is the iron kept by the Haemoglobin ?
Ferrous (reduced)
What happens to the RBC components when broken down by RES ?
- Iron recycled
- Globin broken down in aa
- Heme converted Biliverdin >Bilirubin>Liver bind to sugar >Bile>Stercobilin in faeces or Urobilinogen in urine
Describe the control of erythropoiesis in case of low pO2
Reduced pO2 detected in Peritubular cells in kidney > Increase EPO production > Stimulation of maturation and release of RBC from marrow > Haemoglobin rises > pO2 rises > EPO falls
What are the 2 main metabolic pathways occuring in the RBC ?
Glycolysis : main source of energy
Pentose phosphate pathway / generates NADPH
True or false : We can control how we absorb and excrete iron
Wrong , only how we absorb
What are the 4 forms of Available iron ?
- Haemoglobin (2g)
- Myoglobin
- Tissue iron (cytochrome mitochondrion)
- Transported : Serum iron (3mg)
What are the 2 forms of stored iron ?
Ferritin: soluble
Haemosiderin: Insoluble , in Macrophages (brown)
Approximatively how much iron is lost during a day ?
1-2 mg
Which iron is better ? why ?
Haem iron, because Ferrous form and can enter enterocyte as is
How is the non-haem ferric iron is transformed to ferrous ?
Converted by gastric acid
How is iron absobed and where ?
- Binds to TRANSFERRIN
- Through apical surface in Duodenum and upper Jejunum
Which transporter is involved in iron absorption in intestins ?
DMT1 : divalent metal transporter
How is the iron exported from the enterocyte to blood ?
Ferroportin
Which transporter help absorb iron from milk ?
Lactoferrin
How is the iron taken up in cells from blood ?
Transferrin receptor (TfR) binds the Iron-transferrin complex
Which cell has the highest nbr of TfR ?
Erythroid cells
What food increases and reduces iron absorption ?
- Increases : Vit C , ascorbic acidic : orange juice
- Decreases: Tea, Chapatis,Antacids
How are the dietary iron levels sensed ?
By enterocytes’ villi
What are the absorption control mechanisms ?
- Regulation of transporters
- Expression of receptors (HFE, TfR)
- Hepcidin and cytokines
- Crosstalk between epithelial cells and macrophages …
What is the function of Hepcidin ?
Negative regulator of iron absoprtion and release (macrophages)
When and where is hepcidin produced ?
Made in liver
Excreted by the kidney
When iron overload
How does hepcidin work ?
Binds to Ferroportin on Enterocyte and Macrophages and induce internalisation and degradation of ferroportin preventing absorption and release of iron in blood
what stimulate the rpoduction of hepcidin ?
HFE
TfR
Cytokines
What are the causes of iron deficiency ?
- Insuficcient intake/absorption
- Increased use : physio(pregnancy) or patho(bleeding)
What are the symptoms of iron deficiency ?
- tiredness
- reduced oxygen carrying : Palor, cant exercise
- Cardiac symptoms : angina,palpitations…
What are the signs of iron deficiency ?
Pallor Tachycardia Increased resp rate Epithelial changes (shiny tongue, around mouth) Koilonychia (concave nails)
What are the blood film features and blood parameters in iron deficiency ?
Hypochromic : low haemoglobin content
Microcytic : small RBC and low MCV
Anisopoikilocytosis : change in size and shape
Pencils and target cells
Low serum ferritin ,serum iron and transeferrin saturation
Low reticulocyte haemoglobin content
Which test would you do to determine iron deficiency ?
Ferritin levels (reduced levels indicate iron deficiency) CHR only for functioning iron deficiency but not in thalassaemia
Why does raised or normal Ferritin levels do not exclude iron deficiency ?
Because it s an acute phase protein so raised if inflammation (acute or chronic), malignancy , liver disease and alcoholism
What is the treatment for iron deficiency ?
- Dietary advice
- Iron tablet
- Intramuscular injections
- intravenous iron
- transfusion only if sever anaemia
Why can free iron be dangerous ?
Can exceed Transferrin binding capacity
Reduced iron (ferrous) can produce highly reactive HYDROXYL and LIPID RADICALS > Damage lipid membranes,nucleic acid,proteins
Deposit in tissue
What is haemochromatosis ?
Disorder of iron excess resulting in end organ damage due to iron deposition
What are the consequences of haemochromatosis ?
- Liver cirrhosis
- Diabetes mellitus
- Hypogonadism
- Cardiomyopathy
- Arthropathy
- Skin pigmentation
What is hereditary haemochromatosis due to and treatment ? and inheritance pattern ?
Mutation in HFE gene
Autosomal recessive
Too much iron enters cell
Treat : venesection
What is the role of HFE protein ?
Binds to TfR and compete with Transferrin preventing uptake of Transferrin-Iron complex
State a haemochromatosis disease other than Hereditary H
Transfusion associated haemosiderosis
in transfusion dependent patient (thalassaemia)
Gradual accumulation
State an iron chelating agent
Desferriorxamine
