erythrocytes (rbc’s) ...no organelle –no mitochondria generate energy through anaerobic...
TRANSCRIPT
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 gastransport(transport O2 to tissues and CO2 from tissues)
Hemoglobin reversibly binds with oxygen andmost oxygen in the blood is bound tohemoglobin
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 seems redand 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 ofglucose (2ATP+lactate)
ATP is used as substrate for Na+, K+ or the Ca2+
dependant ATPases that maintain intracellularconcentrations of these cations
The glucose uptake by RBC’s through high affinityglucose 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
Haemoglobin
O2 O2 O2
98% travels in oxyhaemoglobin (in red blood cells)
2% is dissolved in plasma (compared to carbon dioxide, oxygen is relatively insoluble in plasma)
O2 is not very soluble – thus needs a carrier !
O2 O2 O2
Myoglobin, Haemoglobin, Cytochromes bind O2
Oxygen is transported from lungs to various tissuesvia blood in association with haemoglobin
In muscle, haemoglobin gives up O2 to myoglobinwhich has a higher affinity for O2 than heamoglobin
Cytochromes participate in redox reactions and arecomponents of the electron transport chain
Haemoglobin (Hb or Hgb) is the primaryconstituent of RBCs
This molecule gives the characteristic red colourto erythrocytes and to the blood
The primary function of haemoglobin is totransport oxygen (O2) from the lungs to thetissue cells of the body and to carry carbondioxide (CO2)
Hemoglobin (tetramer) iscomposed of the protein globin,made up of two alpha chains (141a.a) and two beta chains (146 a.a),each bound to a heme group
Alpha and beta are similar but notidentical in a.a. sequence
Each heme group bears an atomof iron, which can bind to oneoxygen molecule
Each hemoglobin molecule cantransport 4 molecules of oxygen
Abundant in skeletalmuscles
Consists of one hemeand globin consists ofsingle polypeptidechain (monomeric:153 aa; 17,200 MW)
1. Hb A:o Makes up about 95%-98% of Hb found in adults;
o contains two alpha (α) protein chains and two
beta (β) protein chains
2. Hb A2:o Makes up about 2%-3% of Hb;
o Has two alpha (α) and two delta (δ) protein chains
3. Hb F:
o Makes up to 2% of Hb found in adults;
o Has two alpha (α) and two gamma (γ) protein
chains;
o The primary haemoglobin produced by the
fetus during pregnancy, its production usually
falls to a low level shortly after birth
o Foetal Hb has a higher affinity for oxygen than
adult haemoglobin
o This means that the fetus can receive oxygen
from the mother across the placenta.
Responsible for the O2-
binding capacity of Hb
Consists of an iron (Fe) ion held in a heterocyclic ring, known as a porphyrin
The protoporphyrin made up of four pyrrole rings linked by methane bridges
A Fe atom in its ferrous state (Fe+2) is at the center of protoporphyrin
Fe+2 has 6 coordination bondso 4 bonded to the 4 pyrrole N
atoms (The nucleophilic N prevent oxidation of Fe+2)
o The 2 additional binding sites are one on either side of the hemeplane:
✓ One of these is occupied by the imidazole group of His
✓ The second site can be reversibly occupied by O2
When Hb is bound to O2, it is called oxyHb. This is therelaxed (R ) state
The form with a vacant O2 binding site is calleddeoxyHb and corresponds to the tense (T) state
If iron is in the oxidized state as Fe+3, it is unable tobind O2
R state has a higher affinity for O2
T state is more stable in the absence of O2
conformational change
The subunits slide and rotate making the central cavity smaller
O2-binding curves show Hbsaturation as a function ofthe partial pressure for O2
4 subunits, so 4O2-bindingsites: If one heme group hasa bound O2, it increases theability of the other hemegroups to bind O2 (last O2
affinity is 300 times greaterthan its affinity for 1st O2)
Cooperative binding
Segmoidal curve
Myoglobin has a higher O2
affinity than Hb
Myoglobin O2 dissociation curve is hyperbolic
A number of factors reduce the affinity of Hb for O2 so that more O2 is released to tissues
As the curve shifts from A toB (to right) the affinity forO2 decreases
H+, PCO2, and BPG modifythe structure of Hb and alterits affinity for oxygen:
Increases of these factors:
◦ Decrease hemoglobin’saffinity for oxygen
◦ Enhance oxygen unloadingfrom the blood
Decreases act in the oppositemanner
A number of factors reduce the affinity of Hb for O2 so that more O2 is released to tissues
Increasing temperature also shift the curve to the right
CO2 in blood present in 3 forms:
1. 7% dissolved in plasma
2. 70% travels as HCO3- ions
(hydrogencarbonate ions)
3. 23% travels as carboamino compounds
In red blood cells
CO2 = waste product of cellular metabolism (the end-product)
CO2 reacts directly with Hb to form the carboaminoHb;
reversible reaction
Small quantity of CO2 reacts with plasma proteins -
less significant (quantity of proteins 1/4th that of Hb)
R N H
H
+ CO2 R N H
COO-
+ H+
Carboamino compoundProtein
Dissolved CO2 in blood reacts with water to form Carbonic Acid
CO2 + H2O H2CO3 H+ + HCO3-
Carbonic Anhydrase present inside RBCs (but not plasma) catalyzes this reaction
Carbonic acid rapidly dissociates into ion H+ and bicarbonate ion
Bohr ShiftThe relationship between the binding of O2, H
+, CO2 to hemoglobin (allosteric site), is knowing as Bohr effect
H2CO3
(carbonic acid)
H+
Trapped in cytoplasm
acidification in the red blood cell
Bohr Shift
HCO-3
Leaves the red blood cell
CO2 enters the
blood
Tissues
With high level of activity
Hb
affinity with O2
Release of O2
The dissociation curve moves to the right at higherconcentration of carbon dioxide. This shows that carbondioxide lowers the affinity of Hb for oxygen.
Hb tends to give up O2 in area of high CO2 such as therespiring tissues that need it most.
The build up of hydrogen carbonate ions causesthem to diffuse out of the RBC leaving the inside ofthe RBC positively charged
In order to balance this electric charge chloride ionsdiffuse into the RBCs from the plasma → this isknown as the chloride shift
When blood gets to the lungs, all the reactionsare reversed
The hydrogen carbonate and hydrogen ionsrecombine releasing CO2
The chloride shift is reversed
Carbamino-haemoglobin breaks down torelease CO2
Figure 27–7
Hemoglobin acts as a buffer in blood by picking up CO2 or H+
In tissues:
Hemoglobin becomes more basic when it is deoxygenated, i.e. it binds H+ more tightly
In the lung:
Hemoglobin is oxygenated, becomes more acidic, (i.e. it is a more powerful H+ donor), and releases its H+
SenescentRBCs
LIVER
Bilirubin diglucuronide(water-soluble)
2 UDP-glucuronic acid
via bile duct to intestine
Stercobilinexcreted in feces
Glucuronic acid is removed and bilirubin is converted to urobilinogen which is then oxidized by intestinal bacteria
KIDNEY
Urobilinexcreted in urine
CO
Biliverdin
Heme oxygenase
O2
Bilirubin (water-insoluble)
NADP+
NADPH
Biliverdinreductase
Heme
Globin
Hemoglobin
reabsorbedinto blood (Portion of
urobilinogen)
Bilirubin (water-insoluble)
via blood to the liver (complexed with albumin)
INTESTINE
Catabolism of hemoglobin
Unconjugated bilirubin
Toxic to tissues
Not soluble in aqueous solutions
Tightly complexed to albumin
Cannot be excreted in the urine even when blood levels are high
Conjugated bilirubin
Water-soluble
Non-toxic
Loosely bound to albumin
Excreted in urine (bilirubinuria)
Jaundice describes the yellowing of sclera, skin and mucosal membranes due to increased circulating bilirubin in the plasma
This becomes clinically evident when serum bilirubin reaches about 80-100 mol/l.
A. Hemolytic anemia
excess hemolysis
unconjugated bilirubin(in blood)
Upper normal rangeconjugated bilirubin (released to bile duct)
B. Cirrhosis C. Biliary duct stone
normal unconjugated bilirubin (in blood)
conjugated bilirubin (in blood)
Figure : Examples of hyperbilirubinemia
Hemolytic Jaundice Hepatic jaundice Obstructive jaundice
unconjugated bilirubin(in blood) conjugated bilirubin
secreted by liver into bile
Anemia is due to deficiency of Hb in blooddue to lack of erythrocytes and/or their Hbcontent
Normal Hb concentration
o Adult male =14g/dl (14-17)
o Adult female not pregnant = 12g/dl (12-14)
o Adult female pregnant = 11g/dl (11-12)
What is anemia?
The most common symptom of anemia is
tiredness.
Other signs and symptoms of anemia include:
1. Weakness,
2. pale skin,
3. brittle nails,
4. Dizziness,
5. irritability.
Excess blood loss due to bleeding
Undernutrition: deficiencies of several vitamins andminerals like vitamins A, B2, B6, B12, C, iron, calciumand folic acid along with protein all of which can causeanaemia.
Pregnancy
Others causes: include worm infestation and chronicdisease like AIDS, cancer or kidney disease, cancertreatment, and hereditary diseases
Hemolytic anemia is a disorder in which thered blood cells are destroyed prematurely
RBCs are destroyed faster than the bonemarrow can produce them
Extrinsic:
Red blood cells are produced healthy but arelater destroyed by becoming trapped in thespleen, destroyed by infection, or destroyedfrom drugs that can affect red blood cells
intrinsic:
o The destruction of the red blood cells due to adefect within the red blood cells themselves
o Intrinsic hemolytic anemia is often inherited,such as sickle cell anemia and Glucose-6-Phosphate Dehydrogenase deficiency cells
Sickle Cell anemia is a hereditary disease whichcauses the body to make abnormally shapes redblood cells (“ C “ form)
Causes complications because the blood cells arenot able to reach certain parts of the body
The α chains in mutant Hb (HbS) are the same as in normal Hb (HbA)
A point mutation in the Hb β gene is responsible for the sickling of RBCs seen in sickle cell anemia
Substitution of non polar
valine for a charged Glu
Normal hemoglobin Sickle Cell hemoglobin
No oxygen
No Oxygen: stick together No Oxygen: Separate
No Oxygen
Substitution of non polar valine for a charged Glu
Causes tissue anoxia(Interruption in O2 supply)
This blocking can producemicro vascular occlusionswhich can cause necrosis(death) of the tissue andpain
(25%)(25%)
(50%)
Do not express the disease symptoms
During electrophoresis, HbS moves slowly towards
anode than HbA at alkaline pH
Lysine replaces glutamic acid at position 6 ofthe β globin gene.
Mild chronic haemolytic anaemia
Mixture of Sickle hemoglobin (Hb S) + (Hb C)
Thalassemia is inherited disorders characterizedreduced or absent amounts of hemoglobin
Two major types of thalassemia:
1. Alpha (α): Caused by defect in rate of synthesis ofalpha chains (usually caused by gene deletion)
2. Beta (β): Caused by defect in rate of synthesis inbeta chains (usually caused by mutation)
Absence of 1 α gene (silent carrier): no symptoms, may be slightlyanemia, does not require therapy
Absence of 2 α gene (α Thalassemia trait): no serious symptoms,except slight anemia
Absence of 3 α genes (Hb H disease): microcytic anemia (small RBC),splenomegaly
Absence of 4 α genes (Hydrops fetalis): most serious form, deathbefore birth
Usually caused by point mutations and short insertionsor deletions limited to a few nucleotides
Two situations have clearly to be distinguished:1. βo thalassemia: No β-globin chain is made
2. β+ thalassemia: decreased β-globin chain is made
Disease results in an over-production of α-globin chains, which precipitate in the cells
Folic Acid (also known as vitamin B9) Deficiency causes
megaloblastic anemia (RBCs that are large and fewer
in number)
It occurs due to the inhibition of DNA synthesis during
RBC production, where the cell cycle cannot progress
from G2 phase to mitotic phase.
As a result megaloblasts and immature RBCs are
formed.
Its deficiency can be due to:
1. Poor dietary intake
2. Malabsorption syndromes
3. Drugs that inhibit absorption
4. Alcohol abuse
5. Hemodialysis
6. Increased requirement (pregnancy)
Vitamin B12 is a water soluble vitamin with a key rolein the normal functioning of the brain and nervoussystem, and for the formation of blood
It is also known as pernicious anemia
It is a type of megaloblastic anemia due tomalabsorption of Vit B12 (decreased gastric intrinsicfactor IF which is needed for absorption of vit B12)
The primary defect is a reduction in or
depletion of hematopoietic precursor stem
cells with decreased production of all cell lines.
Aplastic anemia is a severe, life threatening
syndrome in which production of
erythrocytes, WBCs, and platelets has failed.
Aplastic anemia may occur in all age groups
and both genders.
Incidence (acquired)
◦ 2/1000000
◦ rare < 1 year; plateaus 20-60 yrs; increase > 60 yrs
The disease is characterized by peripheral
pancytopenia and accompanied by a
hypocellular bone marrow.