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RBCs are flattened biconcave discs
◦ Flexible structure
◦ Shape provides increased surface area for
diffusion
7.5 µm diameter, 2.5 µm thick
Life cycle – 120 days
Lack a nucleus and other organelles.
33% of weight is hemoglobin molecules (Each
RBC contains 280 million hemoglobins).
Other proteins include antioxidants and those to
maintain RBC shape (spectrin)
Erythrocytes are dedicated to respiratory gas transport (transport O2 to tissues and CO2 from tissues)
Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin
Erythrocyte Function
Is a very elastic , semi-permeable lipid bi-layersupported by a mesh-like cytoskeleton
Is a three layer structure:1. an outer hydrophilic portion:glycolipid, glycoprotein and protein
2. a central hydrophobic layer:
protein, cholesterol and PL
3. an inner hydrophilic layer:containing protein
Several proteins are present in the RBC’s
Integral membrane proteins:Extend from outer surface andtransverse entire membrane to innersurface
Peripheral proteins:
Limited to cytoplasmic surface ofmembrane and forms the RBCcytoskeleton
Glycophorin:
Is the principle RBC glycoprotein. Spans entirethickness of lipid bilayer and appears on externalsurface of RBC membrane
Three types of glycophorins identified: A, B, and C
All glycophorins carry RBC antigens and are receptors or transport proteins
Cytoskeleton:
Network of proteins on the inner surface of theplasma membrane, called the peripheral membraneproteins
Provides rigid support and stability to lipid bilayer
Responsible for maintaining shape and deformabilityof RBC
The most abundant peripheral protein
Flexible, rod like molecule composed of an alpha helix of two
polypeptide chains
1. Spectrin
Microfilaments strengthen membrane, protecting cell from being
broken
Controls biconcave shape and deformability of cell
Is an important factor in RBC membrane integrity because it binds
with other peripheral proteins to form the skeletal network of
microfilaments on the inner surface of RBC membrane
2. Ankyrin :
Primarily anchors lipid bilayer to membrane skeleton
3. Protein 4.1:
May link the cytoskeleton to the membrane by means of
its associations with glycophorin
4. Actin:
Responsible for contraction and relaxation of membrane
Erythrocyte membrane lipid consists of bilayer ofphospholipids intermingled with molecules ofcholesterol in nearly equal amounts. Also, smallamounts of free fatty acids and glycolipids
Different types of phospholipids are found on the insidelayer than on the outside layer
Abnormalities in the PL may result in decreaseddeformability and decreased red cell survival
Most of glycolipids are located in outer half of lipidbilayer and interact with glycoproteins to form manyof RBC antigens
Cholesterol equally distributed on both sides of lipidbilayer (25% of RBC membrane lipid content)
RBC membrane cholesterol is in continual exchangewith plasma cholesterol
Cholesterol plays important role in regulatingmembrane fluidity and permeability
Accumulation of cholesterol results indecreased deformability and may lead tohemolytic anemia
They occur only on the external surface of the red cell
They occur as glycoproteins or glycolipids
The antigens of ABO bloodgroups are examples ofcarbohydrate membranes
Defective or absent spectrin molecule
Leads to loss of RBC membrane, leading tospherocytosis
Decreased deformability of cell
Increased osmotic fragility
Normal biconcave red cell loses membrane fragments
and adopts a spherical shape
Inflexible cells are trapped in the splenic cords, phagocytosed by macrophages
Hereditary disorder of the RBCs (autosomal dominant
trait)
RBCs assume an elliptical shape, rather than the typical
round shape.
Spectrin abnormality or deficiency of protein 4.1
RBC hemolysis occurs in the spleen, thus
splenectomy corrects the hemolysis, but not the
RBC membrane defect
Nonspecific test forinflammatory process
Anticoagulated blood incalibrated tube; rate ofsedimentation of RBCs in 1h
Normal:◦ <15mm/hmale;
◦ <20mm/h female;
◦ add 10 past age 60
X
Any condition that elevates fibrinogen should elevate ESR.
Dramatically ↑ with infection, malignancy, connective tissue disease. Also ↑ with pregnancy, inflammatory disease, and anemia.
A ↓ ESR is associated with blood diseases in which red blood cells have an irregular or smaller shape that causes slower settling ie: sickle cell anemia
The term erythropoiesis (erythro = RBC, andpoiesis = to make) is used to describe theprocess of RBC formation or production.
In humans, erythropoiesis occurs almostexclusively in the red bone marrow
A hemocytoblast is transformed into a committed cell called theproerythroblast
Proerythroblasts develop into early erythroblasts
The developmental pathway consists of three phases
◦ Phase 1: ribosome synthesis in early erythroblasts
◦ Phase 2: hemoglobin accumulation in late erythroblasts andnormoblasts
◦ Phase 3: ejection of the nucleus from normoblasts and formation ofreticulocytes
Reticulocytes then become mature erythrocytes
Reduces O2
levels in blood
Erythropoietin
stimulates red
bone marrow
Enhanced
erythropoiesis
increases RBC
count
Normal blood oxygen levelsStimulus: Hypoxia /
decreased availability of O2 to
blood/or increased tissue
demands for O2
Start:
Kidney (and liver to a
smaller extent) releases
erythropoietin
Increases
O2-carrying
ability of blood
Hemolysis is the breakage of the RBC’s membrane, causing the
release of the hemoglobin and other internal components into the
surrounding fluid.
Hemolysis is visually detected by showing a pink to red tinge in
serum or plasma
In-vivo hemolysis may be due to pathological conditions, such as
autoimmune hemolytic anemia or transfusion, drugs and
infections…
(a) without hemolysis: red blood cell suspension seemsred and opaque.
(b) without hemolysis: RBCs sedimented spontaneously for60 min. Note that the supernatant is not colored.
(c) hemolysis: RBC suspension become transparent byhemolysis.
(a) (b) (c)
RBC membranes have glycoprotein antigens
These antigens are:
1. Unique to the individual Human Blood Groups
2. Recognized as foreign if transfused into another individual
3. Promoters of agglutination and are referred to as agglutinogens
Presence or absence of these antigens is used to classify bloodgroups
Humans have 30 varieties of naturally occurring RBC antigens butthe important ones are the ABO and the rhesus (Rh) blood systems
According to the ABO blood typing
system there are four different
kinds of blood types depending on
the antigen of the RBC
membrane: A, B, AB or O
ABO blood grouping system
Is the precursor of both A substance (A antigen) and Bsubstance (B antigen)
Is formed by the action of Fucosyl Transferase thatcatalyses addition of fucose residue to the terminalgalactose residue of H substance precursor
Fucose
Added by Fucosyl transferase
H antigen
Is formed by the action of N-acetyl-DGalactosamineTransferase (GalNAC transferase) thatcatalyses addition of GalNAC to the terminal Gal residue ofH substance
GalNAc
(N-Acetyl-D galactosamine)
A antigen
Is formed by the action of Galactosyl Transferase thatcatalyses the transfer of Gal residue to the terminalgalactose residue of H substance
B antigen
D-GalactoseAdded by Galactosyl
transferase
Blood group A
• you have A antigens on the surface of your
RBCs
•and B antibodies in your blood plasma
AB0 blood grouping system
Blood group B
• you have B antigens on the surface of your
RBCs
•and A antibodies in your blood plasma
Blood group O
•you have neither A or B antigens on the
surface of your RBCs
•but you have both A and B antibodies
in your blood plasma
AB0 blood grouping systemBlood group AB
• you have both A and B antigens on the
surface of your RBCs
•no A or B antibodies at all in your blood
plasma
Blood transfusions – who can receive
blood from whom?
People with blood group O: "universal donors“
People with blood group AB: "universal receivers"
How common is your blood type?
46.1%
38.8%
11.1%
3.9%
Is the second most significant blood group system in human
transfusion
Rh antigens are transmembrane proteins
The D antigen (RhD) is the most important
If it is present, the blood is RhD positive (~80% of the population) , if
not it's RhD negative
So, for example, some people in group A will have it, and will therefore
be classed as A+ (or A positive), while the ones that don't, are A- (or A
negative) and so it goes for groups B, AB and O
A person with Rh+ blood can receive blood from a person with Rh- blood without any problems
A person with Rh- blood can develop Rh antibodies in
the blood plasma if he or she receives blood from a
person with Rh+ blood, whose Rh antigens can trigger
the production of Rh antibodies
hemolysis
Rh- mothers who have had a pregnancy with/are pregnant
with a Rh+ infant are given Rh immune globulin (RhIG) at 28
weeks during pregnancy and within 72 hours after delivery to
prevent sensitization to the D antigen.
It works by binding any fetal red cells with the D antigen
before the mother is able to produce an immune response and
form anti-D IgG
41
Maternal antibodies destroy fetal red blood cells
◦ Results in anemia.
◦ Anemia limits the ability of the blood to carry oxygen to the baby's organs and
tissues.
Baby's responds to the hemolysis by trying to make more red blood
cells very quickly in the bone marrow and the liver and spleen.
◦ Organs enlarge - hepatosplenomegaly.
◦ New red blood cells released prematurely from bone marrow and are unable to
do the work of mature red blood cells.
42
Baby's responds to the hemolysis by trying to make more red blood
cells very quickly in the bone marrow and the liver and spleen.
◦ Organs enlarge - hepatosplenomegaly.
◦ New red blood cells released prematurely from bone marrow and are unable to
do the work of mature red blood cells.
◦ The heart begins to fail and large amounts of fluid build up in the baby's tissues
and organs resulting in a condition known as Hydrops Fetalis. A fetus with
hydrops is at great risk of being stillborn.
43
44
Whole Blood
Blood Component
RBC; PLT(platelets); FFP (Fresh Frozen
Plasma); Leukocyte; concentrate
Use of whole blood is considered to be
a waste of resources
Type of Blood Transfusion
Cellular components
Red cells
Platelets
White cells
Fresh plasma
Fresh frozen plasma
Cryoprecipitate Cryosupernatant
Factor VIII Albumin
Concentrate Immunoglobulins
other concentrates
The preparation of blood components from whole blood
Blood type and Rh factor status crossmatched
Blood transfusion reactions:
◦ Fever and chills within first 15 minutes
◦ hives and itching during or after transfusion
Most dangerous: ABO incompatibility
RBCs clump and block capillaries
Decreased blood flow to vital organs
Manifestations: lumbar, abdominal and/or chest pain,
fever, chills, urticaria, nausea and vomiting
Occurs after 100 – 200 ml of incompatible blood
infused
1. Stop transfusion immediately
2. Continue IV infusion with normal saline
3. Notify physician of client’s signs and symptoms
4. Provide care for client as indicated
5. Complete reaction form according to institution protocol.
6. Obtain urine specimen from client and send for free
hemoglobin.
No organelle – no mitochondria
Generate energy through anaerobic breakdown of glucose (2ATP+lactate)
ATP is used as substrate for Na+, K+ or the Ca2+
dependant ATPases that maintain intracellular concentrations of these cations
The glucose uptake by RBC’s through high affinity glucose transporter is independent on insulin
Four pathways involved in RBC metabolism:
1. Pentose Phosphate Pathway
2. Glycolysis pathway
3. Methemoglobin reductase pathway
4. 2,3 BPG pathway is unique for RBC
In red cells 1,3 BPG is converted to 2,3BPG which unites with oxy Hband helps release of oxygen at tissues.
The rate of synthesis and hydrolysis of 2,3 DPG are very sensitive topH: a fall of pH inhibits mutase and stimulates phosphatase causingdecrease of 2,3 DPG
2,3 BPG pathway
H2O2 glutathioneperoxidase
2 H2O
2 GSHGSSGglutathione
reductase
NADPH + H+NADP+
pentose pathway
Hydrogen peroxide
Aerobic respirationDrugs, fava beans
02-
02
Superoxide radicals
➢ When erythrocytes are exposedto chemicals that generate highlevels of superoxide radicals, GSH(Reduced Glutathione) is requiredto reduce these damagingcompounds
➢Glutathione Peroxidase catalyzesdegradation of organichydroperoxides by reduction, astwo glutathione molecules areoxidized to a disulfide GSSG
➢The PPP is responsible for
maintaining high levels of NADPH
in red blood cells for use as a
reductant in the glutathione
reductase reaction.
Pentose Phosphate Pathway
Detoxification
The major role of PPP in RBCs isthe production of NADPH whichprotect these cells fromoxidative damage by providingGSH for removal of H2O2
Important in maintaining heme iron in the reduced or ferrous
functional state
The metHbFe3+ is reduced to deoxyHbFe2+ by the flavoprotein,
MetHb reductase (MW 185Kda) (NADH cytochrome b5 reductase)
NAD+
NADH+H+ 2 cytob5Fe3+
2 cytob5Fe2+
2 Hb Fe2+
2 met Hb Fe3+
(Glycolysis)
Mutations causes a deficiency in G6PDH (X-linked), with consequent
impairment of NADPH production
Detoxification of H2O2 is inhibited, and cellular damage results - lipid
peroxidation leads to erythrocyte membrane breakdown and
hemolytic anemia.
Most G6PD-deficient individuals are asymptomatic - only in
combination with certain environmental factors (sulfa antibiotics,
herbicides, antimalarials, *divicine) do clinical manifestations occur.
*toxic ingredient of fava beans
RBC Metabolic Pathways Disorders
This deficiency causes the entire glycolysis pathway to cease working so that
little to no ATP is produced
Consequently, the defective red cells are destroyed in the spleen causing
anaemia and the spleen enlarges (splenomegaly) because it is overworked
The excessive destruction of red blood cells (hemolysis) results in the
breakdown of hemoglobin stored in these cells