Erythrocytes (RBC’s)

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.