Erythropoiesis, introduction to microcytic anaemias and Iron Deficiency Anaemia (IDA) Flashcards
What is the defintion of anaemia? [1]
How can you classify anaemia? [3]
Anaemia: Hb level below the reference range for that age and sex*: commonest blood disorder in the world
Anaemia can be classified by RBC size** as normocytic, microcytic or macrocytic. measured in femtolitres
What type of anaemia does Fe deficiency cause? [1]
Iron deficiency anaemia (IDA): (microcytic anaemia)
Affects approximately one billion people!
How can you split the different types of microcytic anaemia?
- *T**halassemia
- *A**naemia of chronic disease
- *I**ron deficiency - most common
- *L**ead poisoning
- *S**ideroblastic anaemia (disorder where the body produces enough iron but is unable to put it into the haemoglobin.)
TAILS!!
Name two roles of iron in body [2]
What is free iron like to cells? [1]
What is the mechansim like for excreting iron? [1]
O2 carriers: Hb in rbc. myoglobin in mycoytes
Co factor in many enzymes: Krebs cycle, catalase, cytochromes
What is free iron like to cells? [1]
toxic !! :( its a pro-oxidant, therefore is highly regulated
What is the mechansim like for excreting iron? [1]
no mechanism !!!
Where is iron absorbed in the gut? [2] Why? [1]
What is different between haem and non haem iron? [1]
How much iron needed ingested per day? [1]
Where is iron absorbed in the gut? [2]
Duodenum and upper jejunum: best absorbed in acidic environment - where get chyme
What is different between haem and non haem iron? [1]
haem iron is more bioavailable and is sourced from chicken / beef / duck.
How much iron needed ingested per day? [1]
10-15mg
Which cell types absorb iron? [1]
Which cell types absorb iron? [1]
Enterocytes - have specific transport proteins
Explain the mechanism of iron absorbtion and transport in the body for haem iron and non haem iron
Haem iron
- Haem iron – (highly bioavailable) absorbed through DMT1
- Fe removed from Haem. Can then be stored as ferritin OR can exit cell through Ferroportin
Non-haem iron:
- Mostly in the form of Fe3+, but only Fe2+ can be absorbed by the enterocyte. Enzyme reductase: Fe3+ à Fe2+
- Enters via DMT1
- Fe removed from Haem. Can then be stored as ferritin OR can exit cell through Ferroportin
Then transferrin transports Fe3+ around body
How can you postively or negatively influence non-haem iron absobrtion/
Vitamin C and citrate improves iron absorb
Negative: antiacids (like gavison), tannins (in tea)
What is the role of hepcidin in the regulation of iron absorption? [1]
What happens to hepcidin levels if have XS iron? [1]
But when else is hepcidin released? [1] why is this clinically significant? [1]
What is the role of hepcidin in the regulation of iron absorption? [1]
Blocks ferroportin (the transporter of Fe2+ into blood) = negative regulator of iron.
Iron excess stimulates hepcidin production, and increased concentrations of the hormone in turn block dietary iron absorption thus preventing further iron loading
Hepcidin is also released in response to inflammation
How does Fe3+ enter cells other than enterocytes? [3]
- Every cell has a transferrin receptor, (Fe3+ is transported on transferrin)
- Fe3+ –> Fe2+
- Fe2+ into cell via DMT1
- either stored as ferritin or exported via ferroportin / taken up by mito
(UNLESS INFLAMMATION OCCURING: CAUSES RELEASE OF HEPCIDIN WHICH BLOCKS FERROPORTIN)
How do we store iron in body? [1]
Where is this mostly occuring? [1]
What is clinicially signficicant about having inflammation and 1? [1]
How do we store iron in body? [1]
Via ferritin (storage protein): hence low serum ferritin is an important diagnostic test for iron deficiency anemia
Where is this mostly occuring? [1]
Liver:
What is clinicially signficicant about having inflammation and 1? [1]
**ferritin is released into the blood during inflammation
THEREFORE can miss deficiency have if high inflammation**
Transferrin is mainly taken up where in the body? [1]
Transferrin is mainly taken up where in the body? [1]
Myeloid tissue / bone marrow (bc rbc are made there - so needs to go for Hb)
What is the first committed cell in erythropeoisis? [1]
What is the pathway from Haematopoietic stem cell (HPSCs) - to erythrocyte? [1]
What is the first committed cell in erythropeoisis? [1]
Proerythroblast
Haematopoietic stem cell (HPSCs) –> common myeloid progenitor cell –> (CMPC)Proerythroblast –> erythroblast –> reticulocyte – > erythocyte
The proerythroblast develops into an (early) erythroblast. The erythroblast then undergoes a sequence of changes where its nucleus progressively shrinks and its cytoplasm becomes filled with haemoglobin (not stained). When full of haemoglobin it is called a normoblast. The normoblast then expels its nucleus and becomes a reticulocyte. Most reticulocytes stay in the marrow and mature into erythrocytes but some may be released into the blood, especially after haemorrhage. Reticulocytes can transport oxygen, just not as efficiently as mature erythrocytes. They can mature into adult RBCs in the circulation
Which substance controls erythropoiesis? [1]
Where is this produced? [1]
How can ^^ cause production of more erythrocytes? [2]
Which substance controls erythropoiesis? [1]
erythropoietin (EPO) - produced in kidney interstitial cells in around proximal tubules.
How can ^^ cause production of more erythrocytes? [2]
- *1. produces production of proerythroblasts
2. speeds up maturation of erythroblasts**
Stages of rbc formation in fetus?
Stages of rbc formation after birth?
Stages of rbc formation in fetus?
- yolk sac (3 weeks)
- liver (6 weeks)
- spleen (8 weeks)
- bone marrow
You Love a Smart Bunny
Stages of rbc formation after birth?
all bones –> üRed cells produced mainly in marrow of membranous bones, such as Vertebrae, Sternum, Ribs, cranial bones and Ilium.
Which type of transporters do rbc use to obtain glucose?
GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
How do rbc get energy? [1]
Which type of transporters do rbc use to obtain glucose?
GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
How do rbc get energy? [1]
RBCs have no mitochondria – so can’t use oxidative metabolism to make ATP. They need ATP to power cell membrane sodium pumps – otherwise cells would swell up and burst.
Make ATP via Anaerobic Glycolysis from glucose : 2 ATP produced
Lactate is pumped out of erythrocyte into plasma, taken up by liver or muscle cells (especially myocardium), and converted back to glucose - similar mechanism to CORI CYCLE in muscle.
Explain the mechanism of how Fe is recylced during rbc breakdown?
Explain the mechanism of how Fe is recylced during rbc breakdown?
splenic macrophages break down old rbc, via action of haem oxygenase.
Fe3+enters circulation carried ontransferrinto be re-used and exits viaferroportin
How does haem degredation occur?
(Iron has already been recycled)
- Haem turns into unconjugated bilirubin
- Liver takes up unconjugated bilirubin, and via bilirubin diglucoronide is conjugated with glucoronic acid
- sent to gall bladder and stored in bile
- goes to gut after secreted.
- bilirubin converted to urobilinogen and then oxidised to stercobilin & excreted in faeces. some urobilinogen is converted to urobilin and excreted in urine
Signs [7] and symptoms [5] of anaemia?
Also: PICA - unusal cravings for non-nutritive substances
What are specific signs associated with anaemia of iron deficiency? [2]
What are specific signs associated with anaemia of vit. B12 deficiency? [1]
What are specific signs associated with anaemia of thelessasmia? [1]
What are specific signs associated with iron deficiency? [2]
- *Koilonychia (**spoon shaped nails)
- *Angular stomatitis** (inflammation of corners of mouth)
What are specific signs associated with anaemia of vit. B12 deficiency? [1]
Glossitis (inflammation of tongue)
What are specific signs associated with anaemia of thelessasmia? [1]
abnormal bone facial development
How can you distinguish if someone has IDA from histology sample? [3]
RBCs are small (microcytic), unequal sizes (anisocytosis) & contain reduced amounts of Hb (hypochromic)
ü
üDecreased mean corpuscular volume (MCV)
üDecreased mean corpuscular haemoglobin (MCH)
üDecreased mean corpuscular haemoglobin concentration (MCHC)
Why is iron deficiency (ID) the most common cause of anaemia in the world? [6]
Primarily in inorganic ferric form (Fe+3):
Many inhibitors inorganic iron absorption in diet – low bioavailability
Most parts of the world ID/IDA secondary to diets with inadequate/poorly bioavailable iron +/- chronic GI blood loss from gut parasites
Life stages with high needs (toddlers, pregnancy, menorrhagia)
Older adults with impaired absorption associated with decreased acid production and/or anti-acid medications (acid promotes iron absorption)
Gastric bypass surgery
Pathological causes of blood loss such as GI malignancy: need to investigate for GI cancers, especially colon cancers
What is urgent to eliminate if you have patient 60+ and has iron deficiency anaemia? [1]
What is urgent to eliminate if you have patient 60+ and has iron deficiency anaemia? [1]
Check for colon cancers / GI malignancy
What is anaemia of inflammation / chronic disease caused by? [3]
Why will iron supplementation not help in patients with this condition?
What is anaemia of inflammation?
- *IL-6 released and causes**
- *1.** produces more hepcidin - which blocks release of Fe2+ out of via ferroportin
2. blocks production of EPO (& therefore rbc production)
3. inhibits production of rbc in bone marrow
Why will iron supplementation not help in patients with this condition?
Problem is with iron being absorbed in gut and iron getting out of macrophages, along with depressed erythropoietin release and erythropoiesis caused by inflammatory cytokines – need to treat cause inflammation
Why might you miss if someone is deficient in iron? [1]
serum ferritin tests are used to diagnoise irone deficiency anaemia. But ferritin is released if have inflammation from the liver - so may mask anaemia
How do you distinguish between IDA and anemia of inflammation / chronic disease?
Measure ferritin levels:
Ferritin levels in IDA: low
Ferritin levels in Inflammation An: high / normal
How do you treat iron deficiency anaemia?
How do you treat iron deficiency anaemia?
Oral iron:
Iron deficiency anaemia treated with one tablet once daily of oral ferrous sulfate, ferrous fumarate or ferrous gluconate and continued for 3 months after iron deficiency is corrected.
If related to diet: dietary analysis and optimising dietary iron sources discussed to prevent recurrence.
Explain what elevated erythrocyte Sedimentation Rate test indicates [1]
Elevated sedimentation rate (ESR) indicates inflammation – can be secondary to infection, auto-immune illness – different labs will have slightly different normal ranges
- Erythrocytes have negative surface charge*
- Ensures that they electrostatically repel each other and do not stick together, particularly in capillaries.*
- Inflammatory cytokines or bacteria in blood increase amount of (positively charged) fibrinogen in plasma*
- Excess fibrinogen binds to red cell membrane and reduces its negative charge, causing RBCs to adhere*
- Therefore, rate of sedimentation increases as clumps of RBCs fall down through test tube more quickly.*
If ferritin in the blood is low it is highly suggestive of WHAT? [1]
If ferritin is high then this is likely to be related to WHAT? [1]
If ferritin in the blood is low it is highly suggestive of WHAT? [1]
IDA
If ferritin is high then this is likely to be related to WHAT? [1]
If ferritin is high then this is difficult to interpret and is likely to be related to inflammation rather than iron overload
Serum iron varies significantly throughout the day with higher levels in the morning and after eating iron containing meals. On its own serum iron is not a very useful measure.
