MEH - Haemopoiesis & Iron Flashcards
What is anaemia?
Low Hb or low total RBC count in the blood
How does the distribution of haemopoiesis change from child to adult? Why is this relevant in cancer?
More widespread child
Adult - skull, sternum, pelvis, vertebrae, skull, ribs
These are the common places for bone mets due to the blood supply and marrow microenvironment that is favourable for cancers
What is the name of a bone marrow biopsy?
Trephine
What is G-CSF?
Granulocyte colony stimulating factor - is a cytokine and hormone
Stimulates granulocytes to be made
What controls haematopoiesis?
Cytokines (interleukins)/Hormones (growth factors)
What are the hormones/cytokines that control:
1) Erythrocytes
2) Megakaryotcytes/platelets
3) Granulocytes
4) Lymphocytes
1) Epo an CM-CSF
2) CM-CSF, TPO
3) G-CSF, GM-CSF
4) ILs TNFs
What is GM-CSF? What three kinds of blood cell does it stimulate?
Erythrocytes
Granulocytes
Megakaryocytes
(myeloid cells)
What is Tpo and what does it stimulate production of?
Thrombopoeitin and stimulates platelets
What is the reticuloendothelial system? Where is it? What are the main RE organs?
Tissues and cells around body that are part of the immune system containing phagocytic cells - destroy old and damaged cells particularly RBCs
Spleen and liver
5 roles of RBC?
Carry O2 Carry Hb Keep Hb in reduced (ferrous) state Generate ATP Maintain osmotic equilibrium
What is the diamter of a RBC? Can a capillary be less than this?
8micrometres
Yes down to 3.5 - RBC need to fold and squeeze through
When is Epo released?
In response to hypoxia
What is the structure of Hb? R state T state? What is the role of the global chains (3)?
2 alpha 2 beta globin chains each with a haem bound
R- relaxed - O2 bound
T - tense - deoxy
Role of globin chains:
1) Prevents haem from oxidation
2) Confers solubilty
3) Permits shape change of molecule for O2 affinity change (R and T)
What is the catabolism of Haem to excretion?
Haem –> bilirubin —> travels to liver with albumin –> conjugated to glucoronic acid —> more soluble —> forms bile –> bile duct –> intestine –> here either formed into stercobilin or urobilinogen (for faeces or urine excretion)
What is Hb recycled to in the liver?
Spleen –> Haem –> bilirubin to live
Globin –> amino acids
What are the two main metabolic pathways of RBCs?
Glycolysis - Glucose metabolised to lactate ATP generated
Pentose phosphate pathway - G6P metabolised, generates NADPH
Why does the RBC use pentose?
As its intermediates can go into glycolysis
As it regernates glutathione which helps protect from Ros as RBC vulnerable to Ros damage - membrane damage particularly
Can we excrete iron?
No
Only lose a bit a day e.g. bleeding
What are two major functions of iron in the body?
Transports and stores oxygen
Integral part of many enzymes - eg. cytochromes
Name some available stores of iron?
Hb
Myoglobin
Tissue iron - cytochromes
Transported iron - serum iron
Name some stored iron, which is soluble which isn’t?
Ferritin - soluble
Haemosiderin - not
Does most iron come from gut absorption or recycling?
Recycling
How are RBC recycled? Where is most iron stored in the liver?
Mostly by splenic macrophages and liver kupffer cells
Most of iron stored in the liver is in hepatocytes
How much iron enters and leaves the body each day?
1-2mg
Why is haem a better source of iron?
Doesn’t need to be reduced to ferrous form as already is ferrous form
How is iron absorbed in the gut (3 major things to remember)?
Absorbed via binding to transferrin –> into enterocyte. Then either stored as ferritin or transported into the blood via ferroportin, then travels with transferrin to cells e.g. to RBC to then be taken up and used in Hb. Taken into RBC by transferrin receptor. Or taken to be stored in liver/muscle
What is the foetal special ferroportin?
lactoferrin - allows transfer of lactose iron from enterocyte cell to blood
What inhibits/increases iron absorption in the gut?
Ascorbic acids (vit C/citric acid) increases
Chelation inhibits - tea, chapatis, antacids
How are dietary iron levels sensed?
By villi of eneterocytes
What 4 ways can iron absorption be controlled?
Regulation of transporters e.g. ferroportin
Expression of receptors e.g. HFE protein (human haemochromatosis protein) has an effect on regulating the interaction between transferrin receptor and transferrin
Hepcidin and cytokines
Cross talk between macrophages and epithelial cells
How does hepcidin work in iron absorption regulation?
negative regulator of iron storage
binds to ferroportin and degrades it
1) So iron can get into gut cell but can’t go further
2) Iron can’t be released from macrophages so can’t be used
Where is hepcidin synthesised and excreted?
Synthesised in liver
Excreted in gut
When is hepcidin synthesis increased and why?
High iron as it acts to reduce usable iron
What is hepcidin regulated by?
HFE
Transferrin receptor
Inflammatory cytokines (increase release)
Iron deficiency is a symptom not a diagnosis - what else must you look for?
Reason - e.g. malnutrition, pregnancy, bleeding e.g. GI
What can happen to the sides of the lips and the nails in anaemia?
Angular stomatitis
Spooning of nails
How do you treat iron deficiency? What is the problem with giving iron IV?
Dietary advice Oral iron supplements IM Iron IV iron - high risk of anaphylaxis Transaction - not unless severe anaemia with imminent cardiac compromise
What response are you looking for with iron deficient anaemia treatment?
Improvement in symptoms
raise of 20g/L Hb in 3 weeks
What is the problem with excess iron - what happens?
When it exceeds the binding capacity of transferrin can be reduced and form hydroxyl and lipid radicals - damage membranes, nucleic acids and proteins
Where is excess iron deposited?
In tissues
What happens in haemochromatosis? How do you treat?
Autosomal recessive mutation in gene HFE
Deposition of iron in organs leading to damage
Pigmented skin
Hereditary or transfusion associated haemosiderosis
Treat with venesection
What is the normal role of HFE?
Normally competes for binding with transferrin on transferrin receptor
Mutated HFE can’t bind so transferrin has no competition
What is a risk of treatment of thalassemia/transfusion dependent anaemias?
Risk of transfusion associated haemosiderosis due to excess iron - iron chelating agents delay but don’t stop effects of iron overload
