Red Blood Cells Flashcards
Where is blood derived from?
Mesoderm
What are the 3 important functions of RBCs?
- Transport oxygen and nutrients
- Control infection
- Hemostasis (osmotic balance, can’t loose blood)
Blood Cell function affects all organs and tissues. Which three organs are the most sensitive to oxygen delivery?
Brain, Heart, Kidney
List 6 organs/tissues affecting blood function and explain how
- Spleen-Removes senescent RBC
- Kidney-Oxygen sensing
- Heart-blood circulation
- Liver-makes clotting proteins/albumins
- Lungs-oxygen/CO2 exchange
- Bone Marrow-source of blood cells, makes them
Red blood cell life span
120 days
blood volume?
Red cell count?
Circulating RBC?
5 L, 5 million/microliter = 25 trillion circulating RBC
Hematocrit
Volume percentage of RBC in blood
PCV=pack cell volume
ECV= erythrocyte cell volume
If dehydrated, plasma fraction on low side, so hematocrit may go up
Why do RBCs stain acidophilic (red)
filled with hemoglobin
young RBC
reticulocyte
Why are RBCs anucleate?
Nucleus takes up lot of space, it would sacrifice flexibility. Spit out just before they leave bone marrow
In addition to non-nucleated, RBCs lose what other important organelles? What are the implications?
Mitochondria, golgi apparatus, and ER. With no mitochondria, can’t use the oxygen they transport because can’t do oxidative metbolism. With no nuclei and organelles, they don’t contain DNA and can’t synthesize RNA. = LIMITED REPAIR CAPABILITIES
Size and shape of RBC
7-8 microns diameter; 1 micron tall; biconcave disc
Variation in size
Anisocytosis
Variation in shape
Poikilocytosis
RBC Color
Chomicity
Measure of variation in red blood cell volume. Often used together with mean cell volume (MCV)
RDW (red cell distribution width)
higher RDW indicate greater variation in size
Heme contains what sized-membrane rings and how many?
4 five membered rings and 4 six membered rings.
What is the state of iron in heme? How many coordinates? Coordinated to what?
Ferrous (2+), four coordinates to nitrogen atoms of histidine chain
Adult hemoglobin 4 subunits (majority)
2 alpha-globin, 2 beta-globin
Hemoglobin, unlike myoglobin, exhibits cooperative binding/release. What is this an example of and how what type of curve does it display?
Allosteric binding-uptake of one ligand influences affinities of other binding sites.
Sigmoidal curve
Myoglobin only binds one oxygen
Hemoglobin has a _____ affinity for oxygen than myoglobin. Hemoglobin is a ______ efficient carrier of of oxygen than myoglobin
lower affinity, more efficient. (since lower affinity, it has an easier time releasing oxygen to parts of bodies that need it!)
Left shift in oxygen dissociation curve
increases hemoglobin affinity for oxygen. holds on tighter to oxygen
Right shift in oxygen dissociation curve
decrease affinity for oxygen. hemoglobin gives up oxygen more readily
P50
the partial pressure of oxygen in the blood where hemoglobin is 50% saturated (PO2 measured in mm Hg)
An increased P50 signals a _____ affinity and a _____ shift in curve
decreased affinity (a larger partial pressure is necessary to maintain 50% oxygen saturation.) and right shift in curve
Direction of curve shift when: increase temperature
right shift (lower affinity for oxygen)
Direction of curve shift when: decrease PCO2
left shift (high affinity for oxygen)
Direction of curve shift when: decrease pH
right shift (lower affinity). Once blow out CO2 in lungs, it no longer binds to hemoglobin, and you increase hemoglobin affinity for oxygen again
Direction of curve shift when: increase in 2,3-Diphosphoglycerate
right shift (lower affinity). Derived from glycolysis intermediate, signals that body needs oxygen. Lower affinity allows oxygen to dissociate
This molecule is produced as a longer adaptation for hypoxia or anemia to regulate Hgb affinity for O2
2-3-Diphosphoglycerate (shuttling of 1,3-diphosphoglycerate–>23DPG in glycolysis)
Fetal hemoglobin
2 alpha-globin, 2-gamma globin
Direction of curve shift when: increase CO
left shift (CO at one of Hgb binding sites increases the oxygen affinity of the other 3 sites, Hgb affinity increases, holding on to its oxygen tighter)
CO Poisoning
binds to heme iron, 240 fold higher affinity than O2
Hbf (fetal) has ______ affinity than adult
higher affinity. needs oxygen, steals from mom
Resistant to effects of 2,3-DPG
HbF
Sickle cell disease is what mutation in which chain? Why is this mutation important?
Point mutation from Glu>Val
insert hydrophobic where shouldn’t be, becomes insoluble because valines will huddle together
RBCs obtain energy from which process?
Glycolysis, only get 2 lousy ATPs and NADH
Relaxed state of hemoglobin has a ________ affinity
higher affinity
Taut state of hemoglobin has a _______ affinity
lower affinity
Iron in heme group is in ferric state (+3)
Methemoglobin
This electron transport hemoprotein enzymes couples with NADH to restore Hb iron to the reduced (+2) state
cytochrome b5 oxidase and reductase
cyt(b5ox) +NADH –> cyt(b5red) + NAD
cyt(b5red) + Hb-Fe3+ –> Hb-Fe2+ + cyt(b5ox)
What supplies the NADH that restores Hb iron to the reduced state?
Glycolysis, it produces NADH and has no better use for it since can’t do metabolism in RBCs!
How does glutathione eliminate reactive oxygen species?
2GSH (reduced) + H2O2 —> GSSG (oxidized) + 2H2O
GSSG + NADPH —> 2GSH + NADP
What is the source of NADPH for reduction of glutathione?
Pentose Phosphate pathway
Glycated Hb, non-enzymatic
Hemogobin A1c
Why is measuring HbA1c (called the A1C test) used to diagnose type 1 and 2 diabetes?
HbA1c is glycated and proprotional to blood glucose levels. It is an integrated measure of glucose control over prolonged period.
Higher A1C level = poor blood sugar control
How many RBCs do we make a day?
200 billion!
This RBC membrane component (protein) gives RBC its rubber-like flexibility
Spectrin (Band 1)
These 2 RBC membrane components anchor spectrin to the membrane
Ankyrin and protein band 4.1
This RBC membrane component is an anion exchanger important for moving bicarbonate in and out
AE-1 (Band 3)
This structure is what spectrin multimers form beneath the plasma membrane to give RBC cytoskeleton its strength and flexibility
Hexagonal lattice
Mutation in either of these three components can cause hereditary spherocytosis and consequently a shorter life span.
Spectrin, Ankyrin, or Band 3 (AE-1. anion exchanger)
Which organ targets abnormally shaped and old red cells?
Spleen
Why does hereditary spheroctyosis RBCs have lower life span?
Can’t properly make membrane, lose it, and can only make a sphere. Contains fragile cell walls, so prone to breakage, lyse more frequently, can’t make it through endothelial cells in spleen. Tend to get eaten by macrophages
This hereditary disease is also due to spectrin, confers resistance to malaria, and most patients are asymptomatic
Hereditary Elliptocytosis
In a patient with hereditary spherocytosis, what would likely increase?
Reticulocyte “brand new car”
What effect does erythropoietin (EPO) have on reticulocyte count and hematocrit?
Increases reticulocyte and maintains hematocrit
Why might you see bilirubin levels increase in hereditary spherocytosis? (signs: causing skin and whites of eyes to turn yellow)
Bilirbubin is the yellow breakdown product of heme. When RBCs get disposed of in spleen, hemoglobin is released, and heme gets broken down into bilirubin. Bilirubin is insoluble in water, so gets bound to albumin and is sent to liver
An osmotic fragility test is done to confirm HS, where patients RBCs are placed in concentrations of saline solution. What would you expect to happen to spherocytes compared to normal RBCs?
Spherocytes do not tolerate weak saline solution, they will burst sooner than normal cells. When RBCs are placed in saline solution, they absorb water until the cell membrane bursts.
What vitamin supplement would you need to take when treating hereditary spherocytosis?
Folic acid
NADPH from pentose phosphate pathway comes from this enzyme
Glucose-6-phosphate dehydrogenase (G6PD)
