Erythropoiesis and Anemia Flashcards
Definion of Erythropoiesis
Formation of Red blood cells
What part of Erythropoiesis takes 7 days?
progenitor cell (pluripotent stem cell) to the release of the reticulocyte in the circulation takes about 7 days
What happens when the reticulocyte is out in the circulation?
Reticulocytes retain remnants of RNA and polyribosomes to continue synthesizing hemoglobin (manufacture protein)
in 48 hours, the RNA and polyribosomes are kick out and the reticulocyte is now a mature erythrocyte
Erythropoietin (EPO)
Influences the rate of RBC production.
Made in the kidney ( this is an exception). Only about 10-15% secreted by the liver.
It is inactivated by the liver
Stimulates progenitor stem cells to differentiate into erythrocytes
Increases the rate of mitosis of RBC precursors.
Lots of EPO, quick mitosis, lots of RBC
What is the clinical danger of a large amount of blood loss?
It takes 7 days for mature erythrocyte (RBC) to be formed and therefore, need to monitor amount of blood for 7 days until it can be replenished.
How are erythrocytes formed?
1) In the presence of EPO (erythropoietin), that is formed in the kidneys in response to hypoxia (O2 deficient), stimulates production of RBC in the bone marrow.
2) Erythroblast loses its nucleus and mitochondria ( phagocytosed by a WBC) and it is an immature reticulocyte. (this takes 7 days)
3) reticulocyte comes out of the bone marrow into circulation and matures into an erythrocyte. within 48 hours
Erythrocyte shape importance
Biconcave shape important because :
Once the ability to repair is lost when RNA and polyrobosomes are removed (no more protein synthesis), the blood cell has no way to repair if damaged.
-The biconcave shape is super flexible, and is resistant to some degree of breaking.
Can pass through narrow capillaries without bursting or blocking the flow
- they can change shape in response to osmotic changes
Hypotonic solution
Swells RBC’s.
Lose too much salt, or too much water in the cell.
Hypertonic solution
Shrinks RBCs. this happens in the presence of increased salt or decreased H20.
Sickle Cell Anemia
Genetic mutation. The Hb crystalizes with a change in O2 concentration (sickness or altitude) and causes the cell to sickle.
These crystalized cells are not flexible, can form clots, and are very sharp and painful.
The reason it still exists is the resistance to malaria.
How long to erythrocytes live?
about 120 days before they are eaten by the spleen and the components are recycled.
Amino acids (made into new proteins), cell membranes, and iron are all recycled.
We only excrete the ‘heme’ part of hemoglobin by converting the heme groups to bilirubin, and excrete them as bile.
Too much of what protein results in jaundice?
What about babies?
Too much bilirubin built up in the blood can cause jaundice.
Babies often born or develop jaundice because in vitro they have a special type of Hb that has more affinity for O2 to steal from mom. As soon as babies take their fist few breaths they are required to start synthesizing their own. Because the liver needs to break up all of the bilirubin in their system, they can become jaundiced because it is a lot of work for their liver.
Treatment : incubate babies with UV light which breaks up the bilirubin so the liver can do a better job and recover faster.
Hemoglobin (HB) Structure
a tetramer of 2x2 proteins, and 4 binding sites for oxygen
Iron Utilization
Absorbed in the diet through the small intestinal wall via active transport ( needs energy).
Transported to the bone marrow, bound to transferrin (chauffeur that drives iron everywhere), and stored within the ferritin (storgae form of iron) which is found in the liver.
Fe is incorpoated into the Hb within the newly formed RBC and relased into circulation
Best way/ most practical way to measure iron clinically
Best way : bone marrow biopsy. This is too invasive to be practical.
Way we look at it : ferritin. Drawbacks ; it is the storage form and therefore, the last thing to drop when we are iron deficient.
What sources of iron can we utilize?
Best : heme, animal iron. our bodies are well adapted for this.
non - heme iron. from plants, still usable.
*many vegs/vegabs do not have a problem with iron which meat eaters might be anemic.
Why do we care if we have enough iron?
We will not make enough blood cells if there is not enough iron to put into them. Not enough blod = not enough O2. Can be fatal!
Explain Iron Metabolism Graphic
1) Iron from the diet is metabolised in the intestine.
2) Iron enters into the plasma (of the cell, membrane?) absobed by active transport.
3) Transferrin transports iron in the plasma and can either go one of 2 ways :
i) stores Fe as ferritin in the liver.
- liver metabolises bilirubin and excretes it in bile
- bilirubin metabolites are excreted in feces and urine.
- iron is recycled and transported to the liver for storage or intoduced to the Bone marrow for RBC production
or
ii) Bone marrow uses Fe to make Hemoglobin (Hb).
- fe –> heme–> Hb –> RBC synthesis
- spleen converts Hb to bilirubin
- liver metabolises bilirubin and excretes it in bile
- bilirubin metabolites are excreted in feces and urine.
- iron is recycled and transported to the liver for storage or intoduced to the Bone marrow for RBC production
Anemia
Definition and general causes
Results when Hb or RBC counts are too low for normal physiological function
Generally caused by increased RBC loss or decreased RBC production
Types of Accelerated RBC loss - Anemia
General Blood loss :
due to hemmorage ( bleeding)
- cells are notmal in size and Hb content but low in number.
Mostly ER situations, heaby menstruation, uterine fibroids.
OR
Hemolytic anemia :
cells rupture at a high rate.
- hereditary due to enzyme mutations, like sickle cell)
- acquired ( malaria, drugs (chemo), parasites, or autoimmune reactions)
Aplastic anemia
Decreased RBC production.
aka bone marrow failure. All cellular elements decreased.
inadequate EPO production.
- no RBC, no WBC production, damaged kidney etc.
Inadequate dietary nutrient anemia
Iron deficiency :
low iron results in few RBC’s that are smaller and contain less Hb than normal cells. Not enough FE stops RBC synthesis - doesn’t want to waste resources to make empty cells.
Folic Acid and B12 deficiency :
- needed for DNA synthesis and cell division
-low levels result in slower protein synthesis resulting in fewer RBCs that are larger than normal due to slow cell division.
- they get locked in the G2 phase and cannot do mitosis.
megaoblasticanemia
Hemoglobin on CBC
amount of Hb in the blood. O2 carrying capacity.
amount per unit volume.
Best for diagnosing anemia
Hematocrit (Hct)
Percentage of RBCs in the given volume of blood.
Cellular component to fluid volume
Not that reliable, to diagnose anemia. changes with hydration.
