RBC Flashcards
Jobs of the RBC
prevent renal loss
carry carbonic anhydrase
buffer for the blood (like other proteins)
what is the role of carbonic anhydrase
allows us to sequester CO2 as bi carbonate
biconcave disc allows for
flexible membrane and they can bend on themselves to move through very tight spaces like where capillaries turn; better exchange for gases as well
as well as enhanced surface area
RBC amount in body and amt of Hgb carried
5.2 M/100 microliters of blood in men
always near carrying cappacity
14-16 gm of hemoglobin on average
production of RBC
begins in yok sac
moves with the incorporation of abdominal contents and then production is taken over by the liver spleen and nodes
finally this moves to the bone marrow in around the 8th or 9th month of life and this is the final placement of the RBC
role of glycoproteins
give RBC negative charge and repel from other cells or clumping
describe the production of RBC beginning with the stem cell
pluripotent stem cells becomes erythroid progenitor
stops having the potential to turn into other types of cells
the daughter of this progenitor are “committed stem cells”
CFU can be played out from these
most important mediator of RBC production
EPO
this is a renal hormone 90% of it comes from the kidney
what triggers EPO and what is necessary for this production
Sympathetic response -(bleeding)
need B12 and folic acid for the
DNA synthesis and replication
because these cells are very high turnover they require a lot of this for cell division
how does the absence of B12 or folate influence the production of RBC
in the absence of B12 or folate the nucleus foes not keep up with the cytoplasms and doe not do the replication that it needs to
resulting in a large cell
macrocytic anemia
pernicious anemia
failure to absorb B 12 leads to pernicious anemia
in order to absorb we need a intrinsic factor that will bind and carry for absorption in the intestine
atrophic stomach
bipass surgery
autoimmune deficiency can destroy intrinsic factor and limit absorption
can lead to pernicious anemia
how does EPO influence RBC growth
what happens if EPO does not exist
CFU and common erythropoytin cells that express the EPO receptor
the EPO is a growth factor that stimulates the final differentiation of the stem cells
in the absence of these cells die
EPO receptor
how it works when activated
what are JAK and STAT
homodrimeric
formed from two proteins
when bound there is a confirmation change that will stimulate tyrosine kinase molecule activity in cytoplasm
two transcription factors will induce transcription that will lead to the completion of the differentiation process
JAK and STAT are these two factors
two lineages that arise from pluripotent stem cell
lymphoid stem cell (only lymphocytes)
myeloid stem cells
can have cancers in both of these lineages
erythrocyte is part of what lineage
myeloid stem cell lineage
a lot of steps in between myeloid cell and erythrocyte
what is the preerythroblast
where is it located and what role does it play
first cell to make Hgb
confined to the bone marrow
WILL NOT FIND IN BLOOD
will move through stages of development
proerythroblast will force organelles like the nucleus out and the nucleus will become pyknotic
as the Hgb levels increase the cell will get smaller
basophil erythroblast
will stain with basic dyes because it is acidic on the inside hence the name
(BLUE)
this is the intermediate in between the proerythrobalst and the reticulocyte
reticulocyte
baby RBC
nucleus and protein apparatus/machinery is gone
DOES NOT HAVE A NUCLEUS
contains a few polyribosomes and continues to make protein after nucleus is gone based on mRNA left over
(Hgb levels will continue to rise)
will be able to move into the blood stream and will speak to how aggressively the body is trying to pump out RBC and how much EPO is being produced in response to stress
Hgb
speherical tetramer of 4 subunits
pyrroles from succinyl coA and glycine
4 pyrroles form protoporphyrin IX
Addition of iron to protoporhyrin forms Heme
globin polypeptide completes a hemoglobin subunit
(heme plus globin)
which contains iron these are comitted stem cells
HgBA
what is it an what is the prophyrin ring
two alpha and two beta subunits (usually a 1:1 combination)
porphyrin ring on which iron binds nitrogen molecules
2 dimers from the tetrame
majority found in most of us
which type of iron binds ocygen
ferrous Fe2
Fe3 accumulates and causes oxidative stress
methemoglobin
generated by the oxidation of heme to the ferric state causing bluish brown color
high ocygen affinity of methmoglobin means to oxygen is delivered
some globin mutations can stablize iron in this state
you can also get a methemoglobinemia form toxins that oxidize heme orin like nitrate
what is the molecule responsible for stabilizing Hgb prior to oxygen binding
oxygen changes to state of the protein
and keeps 2,3, diphosphoglycerate from stabilizing in unbound state
when this occurs DPG can no longer keep oxygen from binding and the 02 affinity increase
why are RBC not really cells
no nuclei and no mitochondria
this is why we call them erythrocytes
b/c they would steal the O2 from the tissues
very limited protein repair and membrane maintance is allowed but this is in part of the reason why we see such a short lifespan
how does a RBC undergo metabolism
Embden-Myerhof pathway
allows for metabolism
through this glycolytic pathway within the cell
can’t do atp metabolism with oxygen
anaerobic and produces latic acid and 2,3, DPG as biproducts
need glucose form the blood stream and NADH as an essential cofactor
what is required for the Embden-Myerhof pathway
need glucose form the blood stream and NADH as an essential cofactor
pathophys of SCA
hydrophobic
distortion of the sickle due to a valine substitution for a glutamate hemoglobin leads to mishaping after deoxygenation
allow for aggregation of polymers and sickling
how does acidosis and small flow vessels lead to increase intravascular hemolysis with sickle cell anemia
acidosis decreases affinity for oxygen
small low flow vessels
where Hgb has lots of time to dump oxygen
low haptoglobin indicates what
intravascular hemolysis because it is gathering HgB
this recycling can lead to an increase in unconjugated bilirubin
jaundice
also see increase in reticulocytes
complications of SCA
increased reticulocytes leads to an increase in bone formation
stuck in bones causing dactylitis
bone pain
spleenic infarct
oxygen binding influences itself by
a. Loose association of oxygen with hemoglobin molecule
b. Binding of each molecule of oxygen makes hemoglobin more receptive to the next
cellular storage form and what it is composed of
i. Ferritin is the storage form of iron in our body = important
insoluble form of iron that occurs when ferritin is maxed out
hemosiderin
Hypochromic anemia from failure of
transferrin to enter erythroblasts
can’t make chromogen
hypochromic
Can’t make hemoglobin without the iron
Apotransferrin in blood binds Fe
form transferrin (very similar to absorption)
this is how iron is transported
life span of the RBC and how we use this
i. When we do A1c, we are looking at glucose molecules stuck to the hemoglobin molecules
how does the spleen help with the death of RBC
Cells rupture in transit through small spaces, often in the spleen
Spleen is there to recover the old RBCs
many macrophages ingest and return iron to the blood, porphyrin lost as bilirubin
