General Introduction to

Blood
Prepared by
mikurawa
 Composition of blood
• Blood consists of the cells (Corpuscles) suspended
in a clear yellowish fluid called the plasma.

• The cellular elements: 40-45 %

• Three types of cells

– Red blood cells (RBC)/ erythrocytes.
– White blood cells (WBC)/ leucocytes.
– Platelets / thrombocytes.
 The Plasma
• Constitute 55-60% of the total blood volume.

• Made up of water (90%) & dissolved solutes (10%).

• Solid-
a) Organic substances: plasma proteins (7.1%), lipids,
hormones, enzymes, nutrients & waste products (2%).
b) Inorganic substances (0.9%), which include the various
electrolytes e.g. Na, K, Cl, HCO3, Ca, & PO4.

• Gases- O2, CO2 & Nitrogen.

• Serum is a clear straw colored fluid that is similar to

plasma except for the absence of fibrinogen.
 Physical properties of blood

1. Color: red (Hb)

2. PH:
1. Arterial = 7.4
2. Venous = 7.36
3. Blood is opaque due to cellular elements.
4. Specific gravity ≈ 1.060
1. cells= 1.10
2. plasma= 1.026
5. Blood viscosity ≈ 5x that of water (plasma proteins
≈ 2x that of water).
6. Osmotic pressure (OP) of the plasma ≈ 5500
mmHg. (mostly due to crystalloids).

– Plasma proteins OP (plasma colloid OP) ≈ 28 mmHg

– Interstitial fluid proteins ≈ 3mmHg
– The net effective colloid OP (25mmHg) is known as the
Oncotic pressure.
– The total plasma osmolality is 290-300 mOsm/L
– Plasma proteins contribute < 2 mOsm/L
 General functions of the blood
• Blood continuously circulates in the CVS by pumping
action of the heart.

• Blood links the various body systems together & helps

in achieving Homeostasis.

1. It is the major transport medium in the body for,

a. Nutrition- by transporting absorbed food from GIT.
b. Respiration- transp. O2 & CO2.
c. Excretion of waste products from the body.
d. Regulation of metabolism through transport of hormones &
regulating their secretions.
e. Regulation of body temperature.
2. Play an essential role in maintaining the acid-base
balance.

3. Important in the regulation of water balance.

4.Blood viscosity helps in producing peripheral

resistance, which is important in maintaining BP.

5. Blood clotting is a major haemostatic mechanism.

6. Body defense
 The haematocrit (H)
• The % of blood volume that is made up of cells (which are mostly
RBCs) aka packed cell volume (PCV).

• H = (blood cell vol./ total blood vol.) X 100

• Factors affecting H:-

– Changes in RBC vol. relative to plasma vol.
– ↑ in polycythemia, dehydration (haemoconcentration) etc.
– ↓ in anemia, overhydration (haemodilution).
– It is not constant all over- it is less in small than in large vessels due to
plasma skimming, & it is slightly higher in venous blood than arterial
blood due to Chloride shift.

• Determination of H is used in
1. Estimation of blood Vol.
2. Calculation of some blood Indices & diagnosis of anemia.
3. Measurement of renal blood flow.
 The blood volume
• Normal values
– The blood Vol. ≈ 8% of Body weight
– Total blood vol. is ≈ 5.6 Liters in young adult male (70kg) & is less in females.

• Variations in bld. Vol-

– Physiological- pregnancy, high altitude & muscular exercise etc.
– Pathological- polycythemia vera, hemorrhage etc.

• Measurement of the blood vol. (plasma vol. + RBC vol.)

• Measurement of plasma vol. is by dilution technique.

1. Dye method (Evans blue)- a known amount is IV injected & after ≈ 5-10 min.
blood sample is withdrawn, anticoagulated & centrifuged. The conc. Of the
dye in the plasma is determined.
Plasma vol. = amount of dye injected/ plasma conc. After mixing.
2. Isotope method- it is more accurate, radioactive iodine (131I ) can be used.

• Measurement of RBC vol. –radioactive chromium, Iron or Phosphorous can

be used.
 Regulation of the blood volume
• Regulation of the blood cell vol.
– RBC vol. is particularly important in maintaining blood Vol.
– In case of hemorrhage, there can be
I. Rapid compensatory mechanism- RBC are rapidly shifted from stores (eg. Spleen) into
gen. circulation.
II. Slow compensatory mechanism- the rate of erythropoiesis↑.

• Regulation of the plasma vol.

1. Water balance- slow but unlimited mechanism, defends on water loss/ gain.
2. Fluid exchange btw. Plasma & tissue (interstitial) fluid- this is rapid but
limited & defends on the filtering pressures ( Oncotic press., hydrostatic
press., etc.)

• The lymph
– Excess tissue fluid is drain by the lymphatic vessels into the bld circ.
– Its composition is similar to that of plasma but have ↓ prot. Content.
– In the GIT fats are absorbed via the lymph vessels (milky appearance)
– Lymphocytes formed within the lymphoid tissues enter the blood mainly via the
lymphatics.
Haemopoiesis
Prepared by
mikurawa
 Outline
• Haemopoiesis
– Stem cell plasticity
– Characteristics of Stem cells
– Sites of Haemopoiesis
– Regulation of haemopoiesis
– Haemopoietic growth factors
– GF receptors & signal transduction
– Adhesion molecules
– Haemopoietic SC transplant
• Erythropoiesis
– Stages & cell characteristics
– Erythropoietin
– Hemoglobin
• Leucopoiesis
– Formation of Granulocytes
– Formation of Lymphocytes
• Thrombopoiesis
– Stages of production
– Thrombopoietin
 Stem cell plasticity
• Totipotential SCs can generate all tissues of the body

• Pluripotential SCs can generate various types of tissues

• Progenitor cells can differentiate to generate specific tissue

cells.

• BM contain both Haemopoietic SCs and Mesenchymal SCs

• Haemopoietic SCs → Myeloid & Lymphoid series.

• Mesenchymal SCs → muscle, bone, fat, vascular endothelial

and fibrous tissue.
 Haemopoietic stem & progenitor cells
• HP starts with pluripotential SC that can give rise to separate
cell lineages (myeloid/ lymphoid).

• Phenotype of human SC: CD34+, CD38-

• Heamopoietic SC is rare (1 in every 20 million cells in BM).

• Has the appearance of a small or medium-sized lymphocytes.

• Cell differentiation starts from the SC through the committed

haemopoietic progenitor cells which are restricted in their
potentials.
 Characteristics of SC

• Self-renewal: The overall cellularity remains relatively

constant.

• Differentiation:

• Lineage selection:

• Considerable Amplification: One stem cell is capable of

producing ≈106 mature blood cells after only about 20 cell
division.

• The precursor cells are capable of responding to

haemopoietic growth factors (GF).
 Sites of Haemopoiesis (HP)
• These are the organs where HP occur.

• In the first few weeks of gestation- yolk sac

• Stem cells were also observed on the dorsal aorta termed the AGM
(aorta-gonads-mesonephros)

• These common precursors are believed to later seed the liver,

spleen & BM.

• During normal childhood & adult life the marrow is the only
source of new blood cells.

• The developing cells are situated outside the BM sinuses &

matured cells when formed are released into the sinus spaces,
microcirculation & into the general circulation.
 Haemopoiesis

• Is the process of formation of all blood cells.

• Erythropoiesis- is the process of formation of

mature red blood cells.

• Leucopoiesis - is the process of formation of white

blood cells.

• Thrombopoiesis - is the process of formation of

platelets blood cells.
26
 Bone Marrow (BM)
• BM is the main site of blood cell formation.

• In early fetal life blood cells are formed in the liver &
spleen (extramedullary haemopoiesis).

• In adults, RBC, platelets & most WBC are formed in the

bone marrow (medullary haemopoiesis).

• The BM contains multipotent uncommitted SC

(Undifferentiated mesenchymal cells) that differentiate into
committed SC, & later differentiate into the various cell
types found in the marrow & blood.
• Normally ≈ 75% of the marrow cells are leucocytes-
producing cells & only 25% are maturing RBC (although
RBC count is >500x that of WBC).

• In children the marrow of all bones is active (red marrow),

how ever this decreases gradually.

• At 20yrs the red marrow becomes confined to the flat bones

(eg. Sternum, ribs, & vertebra) & the upper parts of long
bones.

• The shafts of long bones are infiltrated by fat & becomes

inactive (yellow marrow).

• In disease conditions the fatty marrow & extramedullary

sites can resume their fetal haemopoietic role.
 Bone Marrow Stroma
• BM forms a suitable environment for SC survival, growth &
development.

• Stromal cells
– Adipocytes- contain fat
– Fibroblast- collagen, glycoprot. & glycosaminoglycans to form extracellular
matrix.
– endothelial cells-
– Macrophages- inflammation & immunity
– microvascular network- blood circulation & nutrition

• In addition, stromal cells secrete several Growth Factors (GF)

necessary for SC survival.

• Few SC can be found in the peripheral blood circulation.

• Several critical interactions maintain SC viability and production.

 Regulation of Haemopoiesis

• HP starts with SC division (self renewal).

• The early committed progenitors express low levels of transcription factors

(TF) that may commit them to discrete cell lineages.

• The cell lineage selected defends both on chance & external signals .

• Cell cycle is a complex process that lies at the heart of haemopoiesis.

• Cell cycle may be allowed to progress or be blocked by Apoptosis .

• Transcription factors regulate gene expression by controlling the

transcription of specific genes or gene families.

• Adhesion molecules are important in mediating the attachment of marrow

precursors, leucocytes & platelets to various components of BM stroma.
 Haemopoietic Growth Factors (GF)
• GFs are glycoprotein hormones that regulate the proliferation
& differentiation of Haemopoietic progenitor cells & the
function of mature cells.

• Mechanisms of action
1. They may act locally (cell-cell) or generally.
2. Bind to extracellular matrix to form niches to which stem &
progenitor cells adhere.
3. They may cause cell proliferation, & also stimulate
differentiation, maturation, prevent apoptosis, & affect the
function of mature cells.
4. They share a No. of common properties
5. Act at different stages of haemopoiesis.
6. The action of one GF on a cell may stimulate production of
another GF or GF receptor (Synergy)
 GF receptors & Signal transduction

• The biological effects of GFs are mediated through

specific receptors on target cells.

• Stromal cells are the major source of GFs, except for

• erythropoietin (90% synthesized in Kidney) &
• thrombopoietin (made largely in the liver).

• GF + receptor → second messenger (e.g. tyrosine

kinase) → changes in gene expression, cell
proliferation & prevention of apoptosis.
 Apoptosis
• Is a regulated process of physiological cell death in which cells are triggered to
activate intracellular proteins that lead to the death of the cell.

• It is an important process that maintains tissue homeostasis.

• Characteristics
– Cell shrinkage
– Condensation of the nuclear chromatin
– Fragmentation of the nucleus
– Cleavage of DNA

• Pro-apoptotic factors
– Fas/TNF → ↑Caspases
– Cytochrome C + Apaf-1 → ↑Caspases
– P53 → ↑ Bax → ↑ Cytochrome C & block cell cycle

• Anti-apoptotic factors
• BCL-2

• The intracellular ratio of Bax & BCL-2 may determine cell susceptibility to
apoptosis
 Adhesion Molecules (AM)
• They are large family of glycoprotein molecules

• AM on the surface of leucocytes may act as receptors &

interact with ligands on the target cell.

• Families of AM
– Immunoglobulin superfamily- receptors which react with Ags.
– Selectins- mediate leucocyte & platelets adhesion to endothelium
during inflammation & coagulation
– Integrins- involve in cell adhesion to extracellular matrix.

• Functions
– Their pattern of expression on tumor cells may determine their
mode of spread & susceptibility to body’s immune defenses.
– May determine whether or not cell circulate in the blood stream
or fixed to tissues.
 Erythropoiesis
• This is the process of origin, development and
maturation of erythrocytes.
• Site of Erythropoiesis
• Before birth
• Mesoblastic stage- 1st trimester, mesenchyme of yolk sac
• Hepatic stage- 2nd trimester, spleen & other lymphoid organs
• Myeloid stage- 3rd trimester, liver & BM
• After birth
• Birth- 20yrs: red bone marrow (RBM) of all bones
• After 20yrs: RBM of axial bones & epiphyses of long bones

46
Important changes during Erythropoiesis

1. Reduction in the size of the cell.

2. Disappearance of nucleoli & nucleus.
3. Appearance of Haemoglobin (Hb).
4. Change in the staining properties of the
cytoplasm.
 Consequences of the changes

• RBCs loose their nuclei & other organells in order to

have more space for Hb.
• Bcos of lack of nuclei & organells, mature RBCs
– do not have DNA, therefore cannot synthesize any RNA,
– have limited repair capabilities & cannot divide.
• Lack mitochondria- do not use the O2 they transport.
• RBC shape- provide laminar flow, minimize platelet
scatter.
• Rate of erythropoiesis: 2 million/ sec. and ≈ 1012
new RBCs are produced daily.
• Life cycle: erythropoiesis takes ≈ 1wk. Circulate in
blood stream for 120 days.
• Reticulocytes forms about 1% of circulating RBCs.
• RBC contain ≈ 2.5 grams of iron or 65% of the
total body iron.
• Each RBC contain ≈ 270 million Hb biomolecules.
• Hb forms a third of the total cell volume & is
responsible for transporting 98% of O2.
 Stages of Erythropoiesis
Stages Size Nucleus Hb Staining
characteristic

Proerythroblast ↑↑↑↑↑ ↑↑↑ absent basophilic

Early normoblast ↑↑↑↑ ↑↑ absent basophilic

Intermediate ↑↑↑ ↑ Starts appearing polychromophilic

normoblast

Late normoblast ↑↑ ↔ ↑ acidophilic

Reticulocytes ↑ absent ↑↑ basophilic

Matured RBC 7.2 μ absent ↑↑ acidophilic

50
Stages of Erythropoiesis
 Factors necessary for Erythropoiesis

A. General factors
 Thyroxin
 Haemopoietic GFs
 Erythropoietin
 Vitamins- vitamins B, C, D, & E.

B. Maturation factors
 Vitamin B12 (cyanocobalamin)
 Intrinsic factor of castle
 Folic acid 52
C. Factors necessary for Hb formation

 Iron – necessary for the formation of heme.

 Amino acids – necessary for the formation of
globin.
 Copper – necessary for the absorption of iron in
the GIT.
 Cobalt & nickel – essential for the utilization of
iron during hemoglobin formation.
 Vitamins (vit. C, riboflavin, nicotinic acid, &
pyridoxine) – essential for the formation of Hb.
53
 Tetraiodothyronine-T4 (Thyroxin)
• Thyroxin is secreted by the thyroid gland
• M.wt = 776.87002 g/mol
• Functions
• Affect the general metabolic rate in the body
• Directly/ indirectly affect most processes in the body
• Specifically increases production of RBCs
 Erythropoietin

• Is a heavily glycosylated polypeptide of 165 aa.

• M.wt of 30,400.

• Source
• Peritubular interstitial cells of the kidney (90%)
• Liver & others (10%)

• Stimulant
• Low O2 tension (hypoxia)

• Erythropoietin stimulates all stages of Erythropoiesis

• May cause bone deformities in infants (e.g. frontal bossing) due to

expansion of RBM.
57
 Folic Acid

• Humans can’t synthesize folate.

• Dietary folate is needed in the synthesis of

purine precursors of DNA.

• In the absence of folate the synthesis of DNA

is reduced leading to the failure of the
maturation of RBCs.
58
 Vitamin B12
• Synthesized in nature by micro-organisms, found in foods of
animal origin.

• Made up of cobalamin compounds, having similar structure with

cobalt atom.

• Act as a coenzyme in the biochemical reactions responsible for

DNA synthesis.

• A normal diet contain a large excess of B12 compared to the daily

need.

• Vit. B12 combines with the intrinsic factor of castle (IF) & the
complex is absorbed through The distal ileum.

• The IF is produced by the gastric parietal cells. 59

Absorption of dietary vitamin B12 after combination with Intrinsic factor (IF), through the
ileum. Folate absorption occurs through the duodenum and jejunum after conversion of all
dietary forms to methyltetrahydrofolate (methyl THF). Transcobalamin II (TC II)
60
 Summary of B12 & Folate
Vitamin B12 Folate

Daily dietary intake 7- 30 μg 200-250 μg

Main foods Animal foods Liver, green leaves & yeast

cooking Little effects Easily destroyed

Minimal adult daily 1-2 μg 100-150 μg

requirement

Body stores 2-3 mg; sufficient for 2-4yrs 10-12 mg; sufficient for 4
months

Site of absorption Distal ileum Duodenum & jejunum

61
 Hemoglobin (Hb)
• It is a chromoprotein with a M.wt. Of 68,000

• Its molecule is globular in shape made up of 4 subunits.

• Each subunit is made up of heme molecule conjugated

to a polypeptide chain.

• The heme is made up of protoporphyrin containing one

ferrous (Fe++) atom.

• Accordingly each Hb molecule contains 4Fe++ atoms &

2 pairs of polypeptide chains, which are collectively
called Globin.
62
Formation of Hb
64
Fig. 2.7 Haem biosynthesis within the immature red cell. Glycine and succinyl
coenzyme A (CoA) combine to form d-aminolaevulinic acid (d-ALA), a reaction
controlled by d-ALA synthase and the coenzyme vitamin B6. d-ALA is converted to
protoporphyrin, which combines with ferrous iron to form haem. The haem molecule
combines with a globin chain. Haemoglobin is formed by a tetramer of these haem–
globin complexes.
Fig. 2.8 Degradation of
haemoglobin. Amino acids from the
globin chains are recycled to
produce new proteins. Iron is
transported by transferrin to the
bone marrow to produce new
erythrocytes. Protoporphyrin is
degraded to bilirubin, which is
insoluble and bound to albumin in
the blood, described as
unconjugated bilirubin, until it
reaches the liver where it is
conjugated to make it water soluble
and excreted in bile. Bilirubin is
excreted in the faeces or oxidised to
urobilinogen to be reabsorbed and
recycled, or excreted in the urine.
67
68
 Normal Hb
• Hemoglobin F (HbF)/ fetal Hb
• replaced by the adult Hb during the first few months of life.
• may persist in some cases of congenital anemia e.g. thalassemia.
• O2 carrying capacity of HbF is much higher than that of normal adult
Hb.

• Adult hemoglobin (HbA)

– 2α & 2β
– ≈ 2.5% of adults contain HbA2 (2α2δ).

• Quantities of Hb
• At birth (25g/dl)
• 3/12 (20g/dl)
• 1 yr (17g/dl) &
• adults (14-16g/dl).

• Sex differences- M (15g/dl), F (14.5g/dl).

 Abnormal Hbs

• Haemoglobinopathies: are congenital abnormalities of

globin chains as a result of substitution of aa, however
most of them are harmless e.g. HbA2, HbC, HbE etc.
• Hb S- val replaces glutamic acid at β6.
• Hb C- substitution of lys for glutamic acid at β6.
• Hb D- glutamine replaces glutamic acid at β121.
• Hb O- lysine replaces glutamic acid β121 .

• Thalassemias

• Abnormal Hb derivatives
 Hemoglobin S (HbS)/ Sickle Hb

• is a very insoluble type of Hb in which the

beta chains are abnormal.
• At low O2 tension it precipitates forming long
crystals which elongates the RBCs.
• RBCs becomes sickle shape.
• The membranes become highly fragile & can
rupture easily, leading to severe anemia (sickle
cell anemia, SCA)
Normal vs. Sickled cell
 Thalassemia
• Thalassemia
– is an inherited congenital disorder of Hb in which the polypeptide chains are
normal in structure but produced in small quantities/ totally absent.
– Can be alpha or beta type.

• There is defective synthesis of either or all of the chains.

• Alpha Thalassemia-
– deletion of one, two, three or all 4 α-globin genes.

• Beta Thalassemia
– β0-thal.- absence of globin chains
– β +-Thal- presence of globin chain (30%)
– The abnormal β-chain genes are denoted β + and β 0 for partial or complete
deficiency, respectively.

• E.gs - Hb G, H, I, Bart’s, etc

 Abnormal Hb Derivatives
• They are formed due to effects of carbon monoxide (CO), Nitrites, Nitrates or
Sulphanamides on Hb.

• Types
– Carboxyhemoglobin (CarboxyHb)- 3-5%
– Methemoglobin (MetHb)- < 3%
– Sulfhemoglobin (SulfHb)- trace

• CarboxyHb-
– Combination of Hb with CO
– Affinity of Hb to CO is ≈ 250x that of O2

• MetHb/ FerriHb-
– The normal ferrous iron (Fe2+) is oxidized to ferric state (Fe3+) by nitrites & nitrates.
– The oxidation is prevented by NADPH system
– Methemoglobinemia → hypoxia

• SulfHb
– When hydrogen sulfide combines with Hb→ excess, green-pigmented SulfHb
– The reaction is ?permanent
 Methemoglobinemia

• Certain drugs & oxidizing agents convert ferrous

(Fe++) in heme to ferric (Fe+++), producing dark
colored compound called metHb. (resembles cyanosis)

• Normally some Hb is oxidized to metHb., but is rapidly

converted back to Hb by the activity of NADH metHb
reductase enzyme system in the RBC.

• Congenital absence of this system leads to excessive

formation of metHb (hereditary methemoglobinemia)
81
 Functions of Hb
• Main fxn of Hb is to transport O2 & CO2
• Act as a buffer.
 O2-Hb combination

• O2 Combines with Fe++ in the heme molecule

forming oxyhemoglobin (oxyHb).

• Each gm of Hb can normally combine with 1.34-

1.39 mls of O2.

• Such combination is loose, occur in a fraction of

seconds, & the iron remains in a ferrous state.

83
84
85
 Iron
• Is an essential mineral involved in the transport of O2.

• It is important in the formation of Hb, myoglobin &

other substances like cytochrome oxidase and
peroxidase.

• Total body iron – 4 g.

• Dietary iron can be in the form of heme/ nonheme Iron.

• Iron is absorbed in ferric form mainly from small

intestine by pinocytosis.
86
• Iron is transported by a β globin called transferrin.

• Iron is stored in large quantities in the body as

ferritin/ haemosiderin.

• A copper containing enzyme caeruloplasmin

catalyses the oxidation of iron to ferric form 4
binding 2 transferrin.

• Body iron demand varies with age & sex, and is

highest in pregnancy & adolescents.
87
88
 Thrombopoiesis
• They are small granulated oval/ round bodies 2-4 μ in
diameter.

• Formed as detached bits from giant cells called

megakaryocytes.

• Their production is regulated by thrombopoietin hormone.

• They may have no nuclei, & have a life span of 8 days.

• Normal count: 150,000- 300,000/ mm3.

• Normally abt. 60- 70 % of platelets is found in the circulating

blood while the remainder in spleen.
1/14/2022 90
1/14/2022 91
 Leukopoiesis
• Most lymphocytes are formed in the lymphoid
organs, while other WBCs in the BM.

• Leukopoiesis requires all the dietary factors

necessary for cell growth & division.

• Leukopoiesis is stimulated by CSFs produced by the

macrophages, fibroblasts, endothelial cells & certain
lymphocytes.

• Most of these GFs act locally in the BM, stimulating

a particular committed stem cells. 93
95
Plasma Proteins
Prepared by
mikurawa
 Introduction
• They include proteins found in blood plasma &
interstitial fluid.
• Almost all are glycoproteins.
• Some of the PP may be separately grouped as
enzymes & proteohormones.
• About > 300 proteins are identified.
• Exist as negatively charged molecules under
physiological conditions.
• Distribution in body fluids defends on,
– Movement across capillary basal membrane (molecular
weight)
– Transport by pinocytosis
• Examples: Albumin, transferrin, Haptoglobin, α2-
macroglobulin, etc.
 Sources of PP
A. Food proteins: they are the most effective for synth.
Of PP bcos.,
 Similar structure wiz that of PP
 Have high biologic value (rich in essential aas)

B. Tissue proteins
I. Fixed proteins- these are indispensable for the life of cells, so
they are not mobilized from the cell & therefore cannot be
converted into PP.
II. Reserve proteins-
I. Dispensable reserve proteins-they can be mobilized to the liver to
produce energy & PP during starvation.
II. Labile reserve proteins-these are structurally similar to the plasma
proteins & can be readily mobilized to the blood stream to maintain
their level constant.
 Prealbumin
• Rich in tryptophan & contain 0.5% CHO
• Transports T3 & T4
• Transports retinol (vitamin A)
 Albumin
• The most abundant
• Serum Albumin (4.7 g/dL)
– M.wt of 69,000

• Serum levels
– birth=39g/L,
– 9months= 28.4g/L,
– adult= 35-55g/L,
– 60yrs= 38.3g/L)

• Responsible for 80% of oncotic pressure

• Binds bilirubin, salicylic acid, F.As, Ca, Mg, cortisol & some
drugs.
 Fibrinogen
• Fibrinogen (0.3 g/dL)
• The least abundant,
• One of the largest glycoprotein in blood plasma.
– M. wt. 400,000.
• Synthesized mainly in the liver
• Main function is the formation of fibrin clot when
activated by thrombin.
• Fibrinogen is totally absent in serum.
 Globulins
• Group of proteins consisting of many fractions
• Serum Globulins (alpha I & II, beta I & II, & gamma globulins)-
• 2.3 g/dL,
• M. wt. 90,000- 156,000.
• α1-Antitrypsin- acute phase reactant
• α1-Fetoprotein (AFP)- protects fetus from immunolytic attack & promotes
growth and development.
• α1-Acid Glycoprotein- components of fibers & inactivates basic hormones like
progesterone
• α1-Antichymotrypsin
• Inter-α-trypsin Inhibitor- proteases inhibitor (trypsin, plasmin, etc).
• Gc-globulin (group specific component; vit. D-binding proteins)
• Haptoglobin
• Ceruloplasmin – contain 90% of serum copper.
• α2 Macroglobulin- found in the intravascular space, inhibits proteases (trypsin,
pepsin, & plasmin) & promotes actions of thrombin
• Transferrin – transports iron & prevents its loss through the kidney.
• Hemopexin – removes circulating heme to the liver.
• β2-Microglobulin – it is the light chain component of MHC (HLA)
• Complement
 C-Reactive Proteins (CRP)

• Synthesized in the liver

• ↑ in tissue necrosis & inflammation
• By binding to molecular groups on wide
variety of bacteria & fungi, CRP promotes
compliment activation & opsonization.
 Compliment
• Is a collective term for several proteins (C2-C9)
that participate in immune reaction.
• They circulate as inactive precursors that can
be activated.
• Functions
– Help in inflammation
– Promote opsonization
 Haptoglobin
• Synthesized in hepatocytes (90%) & RES.
• Haptoglobins binds free Hb by its α- chains.
• Abnormal Hb, having no α- chains (Bart’s)
cannot bind.
• RES removes haptoglobin-Hb complex from
circulation within minutes to prevent loss of
Hb.
 Functions
• Specific
– Transport proteins
– Immunity
– System of proteases & antiproteases
– Coagulation process
– Signal proteins
– Enzymes
– Cellular proteins

• Clinical use
– Cardiomarkers
– Tumor markers
– Acute phase reactants
– Cellular enzymes
– Hormones
– Cytokines
 Factors influencing concentration

• Rate of synthesis & degradation

• Distribution in body fluids
• Loss into the third space
• Rate of elimination from the body
• Hydration of the body
Consequences of abnormal concentrations

• Change in ESR
• Swelling
• Polyuria
• Increased susceptibility to infections
 Synthesis
• Liver – most PP
• Plasma cells – immunoglobulins
 Regulation of synthesis
Increased Decreased
• Inflammation • Liver disease
• Hyperthyroidism • Nutritional deficit
• ↑ stress hormones • Hypothyroidism
• Iron deficiency • Diabetes
• Protein loss • Alcoholism
 Half-life
• Factors affecting half-life
– Is related to function of the protein
– Influenced by distribution of the protein
– Influenced by rate of catabolism & elimination

• Structural proteins- have the longest half-life

• Regulatory proteins- shortest half-life
• Elimination of PP
– Excretion in Urine
– Elimination through the faeces
– Loss through the skin
 Knowledge of PP
• Laboratory determination/ quantification
• Diagnosis
• Help in treatment of certain disorders
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 Plasma proteins (PP)
• The PP include mainly albumin, globulins and
fibrinogen in addition to other small amounts of
proteins (hormones, prothrombin & most of the other
clotting factors).

• The amount averages 7.3 g/dL

1. Serum Albumin (4.7 g/dL)- the most abundant, M.wt of
69,000
2. Serum Globulins (alpha I & II, beta I & II, & gamma
globulins)- (2.3 g/dL), M. wt. 90,000- 156,000.
3. Fibrinogen (0.3 g/dL)- the least abundant, M. wt. 400,000.
 Methods of separation of PP
1. Plasma ultracentrifugation- entails sedimentation of
the various PP at diff. rates.

2. Chemical separation- based on the precipitation of

the various PP. 2 methods
a. Precipitation by salt
b. Fractional precipitation

3. Electric separation (electrophoresis)- this is the

separation of the PP by passing a constant electric
current in the plasma, it is the most accurate
method.
 Site of synthesis of PP
• All PP are synthesized in the liver except gamma
globulin which is synthesized in lymphoid tissue by the
plasma cells.

• During embryonic stage PP are synthesized by the

mesenchymal cells (first Alb. Followed by others)

• In the first 6 months of pregnancy Both Alb. & globulin

decrease while fibrinogen level increases.

• In infancy, the total PP concentration is low (due to low

Alb. Content).
 The Albumin/ globulin ratio
• Normally the A/G ratio is 2:1

• The determination of A/G ratio is clinically

important bcos. It is altered in the following
conditions,
1. ↓ in advanced liver disease, severe infection.
2. ↑ in congenital agammaglobulinemia.
 Functions of PP
1. Haemostatic function
2. Help in the production of blood viscosity 2gather wiz RBC
(esp. fibrinogen & globulins due to their large m.wt.).
3. Their osmotic pressure abt. 28 mmHg is essential for
reabsorption of fluid from tissue spaces.
4. They produce 7- 15% of the buffering power of the blood.
5. Defense (gamma globulins are antibodies)
6. Conservation function
7. Control of capillary permeability
8. Transport of CO2
9. Nutritional function
10. Specific functions
 Specific functions.
Plasma protein Main function

albumin Conservation function, production of

Osmotic pressure, as a transport prot., & as
an antioxidant.

Globulins Conservation function & defence

fibrinogen Blood coagulation & production of blood

viscosity

Globulins & fibrinogen Increase ESR, byfavouring formation of

rouleaux shapes in RBC