Erythrocytes Flashcards
mammalian shape of RBC
discocyte (biconcave disc)
Which in general have a higher RBC mean cell volume: mammals or nonmammals?
nonmammals
Increased total RBC count –> MCV? (In general)
decreases. As number of RBCs increases, they usually also decrease in size
“drepanocyte” means:
sickle shaped. i.e. - deer blood
“dacrocyte” means:
tear shaped. i.e. - goat blood
Camelids have what shape RBC?
elliptocytes
Birds have what shape RBC?
ovalocyte
pigs have what shape RBC?
echinocyte
What causes sickling of RBC?
Single amino acid substitution. Also, a pH drop and oxygen can potentiate sickling
What can cause echinocyte shape in RBC?
1) excess anticoagulant in sample
2) ATP depletion with prolonged storage
3) addition of fatty acids, bile acids, certain drugs
4) disease states
Is echinocyte shape in RBC reversible?
yes
erythrocyte functions
1) transport of oxygen
2) transport of carbon dioxide
3) buffering of H+ ions
blood oxygen content is dependent on:
1) Hb content
2) pO2
3) Hb oxygen affinity (P50)
What is the advantage of releasing O2 to tissues at a higher pO2? (Hb is unloading sooner)
creates a greater gradient for O2 delivery to the tissues
What is the DISadvantage of releasing O2 to tissues at a higher pO2? (Hb is unloading sooner)
won’t be able to fully load the oxygen in the lungs and some of the animal’s Hb won’t even get used
Increased 2,3 DPG –> Hb’s affinity for O2
decreases. Hb releases O2 sooner
How does 2,3 DPG, temperature, CO2, and H+ effect Hb affinity for O2?
If any of them increase, Hb’s affinity for O2 decreases
How do anemic dogs compensate for low Hb?
have higher 2,3-DPG lvls
products of oxidative metabolism at the tissues?
CO2 and acids
Where is binding of O2 to Hb maximized and minimized?
Maximized at the lungs, minimized at the tissues
P50 represents
oxygen affinity. High p50 means lower O2 affinity
Why do smaller animals have higher p50 than larger animals?
they have higher metabolic rates, therefore need more O2 released to tissues rapidly
Why is there higher Hb affinity for O2 in fetal blood than maternal blood?
potentiates O2 delivery from mother to fetus. Fetus normally lives in a hypoxic environment, so it’s ok for their Hb to have a higher affinity for O2
Where is majority of CO2 in body?
bicarbonate in the blood. Acts as a buffer and increases CO2 carrying capacity of blood
Which binds more CO2: deoxyHb or oxyHb?
deoxyHb. Is triggered to bind CO2 once O2 is released
Where is carbonic anhydrase located? what does it do?
In erythrocytes. Catalyzes formation of bicarbonate from CO2 and H2O
major protein buffer in blood
Hb
which is stronger acid: deoxyHb or oxyHb?
OxyHb
what buffers organic acids produced by metabolism?
Hb
What are Heinz bodies?
oxidative denatured Hb
What is glucose ultimately converted to during the process of carbohydrate metabolism?
lactate, with production of ATP. 2,3-DPG is also produced in a side reaction.
What does pentose phosphate pathway generate? Why is it important?
NADPH. It keeps glutathione in a reduced state, which ultimately protects the RBC from oxidative injury
What will glutathione do if its oxidized?
become GSSG by reduction of H2O2
fx of reduced glutathione (GSH)?
free radical scavenger, electron donor for reductive enzyme reactions
What reduces GSSG back to GSH?
NADPH-dependent glutathione reductase
how does selenium act as an antioxidant?
It is incorporated into protective enzymes
how does catalase act as antioxidant?
degrades H2O2
how does ascorbate act as antioxidant?
donates electrons
how does vitamin E act as antioxidant?
membrane free radical scavenger
catalase reaction
H2O2 –> H2O + O2
What happens to H+ released from deoxyHb with CO2?
Combines with HCO3- to form H2CO3, which reversibly forms CO2 and H2O
How does pH change when Hb binds CO2?
only slightly lowers. Hb allows for transport of CO2 with only a slight change in pH
Describe composition and orientation of erythrocyte membrane lipids
phospholipid bilayer with hydrophobic hydrocarbon chains of fatty acids directed to the center of the bilayer. Unesterified cholesterol intercalated with FA chains. Glycolipids in the outer layer containing blood group antigens
Integral vs. skeletal membrane proteins on erythrocytes
integral memb. proteins are transmembrane glycoproteins that include receptors, transport proteins, and erythrocyte antigens.
Skeletal memb. proteins form a lattice-like arrangement on inner surface of membrane that allow for a fluid lipid bilayer
where are blood group antigens produced? What are they composed of and why are they important?
erythroid cells. Composed mainly of carbs. important for animal ID and parentage testing. Most blood group antigens are the same across members of a species
clinically significant blood group antigens in horses
A and Q factors
clinically significant blood group antigens in dogs
DEA (dog erythrocyte antigen), and Dal (lacking in some Dalmations)
clinically significant blood group Ag in cats
AB group, Mik group
what are natural antibodies?
antibodies present BEFORE you give a transfusion. Most likely arise from carbs present on gut flora seen by the immune system, however they have never had exposure to the foreign RBC!
Erythrocyte method of metabolism
in absence of ribosomes, mitochondria, and ER, they utilize glucose in glycolysis and pentose phosphate pathway for energy.
Does DPG cycle generate net ATP gain?
NO
What are RBC’s energy requirements?
1) maintain Na and K concentrations
2) maintain shape and deformability
3) maintain 2,3-DPG concentrations
4) MetHb reduction
5) pentose phosphate pathway to protect against oxidant injury
oxidant damgae to Hb/enzymes/membrane unsaturated lipids can result in:
MetHb, heinz bodies, increased phagocytosis, intravascular hemolysis
difference between MetHb and Hb
MetHb has Fe in +3 state instead of +2 state, so it can’t bind O2. This is a natural product of neutrophil activation
What converts MetHb back to normal Hb?
Cb5R. FAD is a cofactor for this process
What is majority of Fe in the body used for? **
RBC production. Majority of the body’s iron is located in the RBCs ***
where is transferring produced?
liver
Where does majority of recycled Fe come from?
Macrophages, which break down old RBCs
True or False: Fe is highly conserved in the body
True
What brings Fe to developing RBCs?
transferrin
What stores Fe absorbed from the intestine?
interocytes. Stores Fe as ferritin
Fe+3 =
ferric iron
Fe+2 =
ferrous iron
What solubilizes Fe from food in the stomach?
HCl. Mucin helps keep it solubilized
2 mechanisms to absorb Fe into a RBC
1) Fe is reduced, then transported into cell via DcytB and divalent transporter
2) Heme carrier protein takes heme molecule in with bound Fe. Heme oxidase then breaks down and releases Fe into the cell
What converts Fe+2 to Fe+3?
hephaestin
what transports Fe out of RBC?
ferroportin
Why is too much Fe in blood bad?
Can be toxic and act as a free catalyst
If there is too much Fe entering a RBC, how is this compensated for?
Fe is stored as ferritin (a protein shell filled with Fe+3). This protects cell from damage
hepcidin fx
Inhibits ferroportin from depositing Fe into the body from the RBC. Increases when there is too much Fe in the body. Cell with excess Fe will then slough in the GI tract
inflammation –> iron absorption
decreases
increased erythropoiesis –> hepcidin release
decreased. Erythropoiesis requires more Fe to be available
Can hepcidin be increased even if Fe is low?
Yes.
Total iron binding capacity is a measure of:
transferrin concentration
Almost all Fe is bound to:
transferrin
Which binds Fe better: diferric or monoferric transferrin?
diferric. It can also deliver Fe to the body more efficiently
Majority of plasma iron is utilized for:
Hb synthesis. It mostly comes from macrophage release
where is heme formed?
inside mitochondria of RBC
Where is Hb formed?
in cytoplasm of RBC (heme leaves mitochondria and combines with globin)
Do reticulocytes have mitochondria?
Yes
What does hepsidin control?
How much Fe is present in the whole body. Master regulator of Fe homeostasis
apoferritin fx
intracellular Fe storing protein
TfR =
transferrin receptor. Carrier protein for transferrin that imports Fe into the cell
When is TfR expression promoted?
under conditions of low Fe content inside the cells
ceruplasmin fx
copper containing plasma protein that converts Fe from +2 to +3 state. (+3 state binds to transferrin)
Increased hepcidin –> Fe absorption
inhibited
hemosiderin
aggregates of protein and iron in lysosomes in a macrophage
increased intracellular Fe concentration –> apoferritin synthesis
increases
3 mechs of transporting Fe into the cytoplasm
1) DMT1 (used by duodenal enterocytes)
2) phagocytized erythrocytes (used by macrophages)
3) transferrin endocytosis (used by RBCs and other cells)
1 Hb binds ___ O2 molecules?
4
1st step in heme synthesis
formation of ALA. Occurs in the mitochondria
last step of heme synthesis
insertion of Fe into the heme group. Occurs in the mitochondria
Synthesis of globin monomers is promoted by:
increased free heme
increased free heme –> iron uptake by erythroid cells
inhibits
RBC lifespan in large vs. small animals
longer in large animals. Slower metabolism doesn’t acquire as much damage to RBCs as quickly
Eryptosis
apoptosis in anucleated cells
band 3
an anion transporter that clusters to form a senescent antigen in old RBCs and mark them for destruction by macrophages
Signs of an aging RBC
1) altered phospholipids (increased surface PS)
2) altered carbs
3) altered proteins (partially degraded band 3)
High lvl of CO in the body indicates:
high lvl of RBC destruction
Where/how is CO produced in the body?
Inside macrophage when heme is broken down into biliverdin
biliverdin reductase
converts biliverdin to bilirubin
physiologic anemia
normal dropoff in Hb lvl post-partum. Animal can become anemic and Fe deficient
why does erythropoietin decrease post-partum?
at birth there are high red cells, oxygen, and 2,3-DPG due to recent transfusion of cord blood. Therefore, additional RBCs are not needed. (this short-lived however with increasing growth)
lifespan of adult vs. fetal RBCs
adult RBCs have longer lifespan
