Blood Cells, Immunity

and
Blood Clotting
• Blood is special biological fluid important for life.

• Blood consists
– formed elements
– Watery plasma
• Formed elements are
• erythrocytes,
• leukocytes, and
• Platelets

• They are suspended and carried in plasma.

• Plasma contains different types of proteins and

many water-soluble molecules
• The total blood volume
– ≈ 5 liters in average adult (8% of total body weight) and
– ≈ 300 milliliters in neonate immediately after birth

Functions of the blood

• The transportation of dissolved gases, nutrients, hormones, and

metabolic wastes.

• The regulation of the pH and electrolyte composition of

interstitial fluids throughout the body.

• The protect body fluid losses through damaged vessels or at

other injury sites.

• Defense against pathogens ( infectious agents) and toxins.

• Stabilization of body temperature.

• Hematopoiesis: formation and development of the
blood cells from hematopoietic stem cell.

• In humans, this process begins in the yolk sac in 1st

weeks of embryonic stage

• By 3rd month of gestation, stem cells migrate to the

fetal liver and then to the spleen.

• Between 3-7 months gestation these two organs play

a major hempatopoietic role).

• Next, the bone marrow becomes the major

hematopoietic organ.
• The path of stem cells differentiation is determined by
– body demand for a specific type of cells and
– this in turn controlled by cytokines or hormones .

• Interleukin-7: stem cells to various lymphocyte

• Erythropoietin for the production of red blood cells

• Thrombopoietin with Interleukin-11, for megakaryocytes,

which gives platelets.

• Granulocyte colony-stimulating factor (G-CSF) for

neutrophils.

• Interleukin-5 for eosinophils

• Interleukin-3 for formation of basophils

• Formation of different blood cells from pluripotent stem cell
• When a blood sample is centrifuged,
– the heavier formed elements packed at the bottom
– and plasma float on top. The

• The formed elements constitute ≈ 45% of the

total blood volume and plasma accounts ≈55%.

• Hematocrit is percent of blood occupied by

blood cells (esp. RBC)
• The constituents of blood.
• Plasma
– straw-colored liquid
– consisting of water and dissolved solutes.

• The major solute of the plasma is Na+.

• Plasma also contains many other ions,

nutrients, gases, metabolic wastes, proteins,
hormones.

• Straw(yellow) color of plasma is due to billirubin

• Plasma Volume regulated by a number of regulatory
mechanisms to maintain homeostasis.

• If the body lose water, plasma becomes

concentrated.

• This is detected by osmoreceptors in the

hypothalamus, resulting in a sensation of thirst and the
release of antidiuretic hormone (ADH).

• This hormone promotes water reabsorption by the

kidneys, which together with  intake of fluids
compensate for the dehydration

• This is important in maintaining blood pressure.

• Normal plasma values
• Plasma Proteins
• Constitute 7% to 9% of the plasma.

• The three major types of proteins are

• albumins,
• globulins, and
• fibrinogen.
•
• Albumins
• account for most (60% to 80%) of the plasma proteins and
• The smallest in size.
• Produced by the liver and released to circulation
• Provide the osmotic pressure needed to draw water from
interstitium to capillaries.
• This action is needed to maintain blood volume and pressure.
• Also binds many small molecules for transport through the
blood
• Globulins
• Grouped into three subtypes:
• alpha globulins,
• beta globulins, and
• gamma globulins.

• The alpha and beta globulins are produced by the liver

• Function in transporting lipids and fat-soluble vitamins.
• Eg. alpha globulins transport thyroxine and retinol [vitamin A])
beta globulins transport iron-caring protein transferrin)

• Gamma globulins are produced by lymphocytes and least -Vely

charged
• Help to form antibodies and function in immunity.
• Fibrinogen

• Accounts ≈ 4% of the total plasma proteins.

• Important clotting factor produced by the liver.

• During clot formation, fibrinogen is converted into insoluble

threads of fibrin.

• The fibrin help to repair damaged blood vessel.

• Serum is plasma devoid of fibrinogen.

• Red Blood Cells (Erythrocytes).
• They most numerous type of the blood cell.
– blood contains 5.1 million/ml to 5.8 million/ml RBC in males
and 4.3 million/ml to 5.2 million/ml RBC in females.
– Gives hematocrit value about 42% for females & 45% for
males
– these values can vary depending on such factors as health
and altitude
• eg. Dehydration, polycythemia, higher altitude etc… hematocrit
Anemia decrease hematocrit
– By contrast, blood contains only 5,000 to 9,000WBC per ml.
• Mature RBC
– have biconcave discs shape
– have no mitochondria thus do not use O2 for respiration
– use anaerobic respiration and have many enzymes for
glycolysis
– lack a nucleus & cannot reproduce in circulation
– have average lifespan ≈ 120 days
– contain hemoglobin for O2 ,CO2 and H+ transport
– has ≈280 million hemoglobin molecules per RBC
– have surface antigens on cell membrane that differ between
people( help for blood grouping)
– Contain enzyme carbonic anhydrase(critical for CO2
transport
• carbonic anhydrase, catalyzes the reversible reaction
between CO2) and H2O to form H2CO3).

• Increasing the rate of this reaction help to transport

enormous quantities of CO2 in the form of bicarbonate
ion (HCO3 –) from the tissues to the lungs.

• In the lung the reaction is reversed thus CO2 expelled

into the atmosphere as a body waste product.

• The hemoglobin in the cells is an excellent acid-base

buffer as it bind H+
• Production of Red Blood Cells.

• Bone marrow of almost all bones produces RBC until

age of 5.

• The marrow of the long bones, becomes fatty &

produces no more RBC after age 20 years.
– except proximal portions of the humeri and tibiae, Beyond
this age,

• Most RBC continue to be produced in the marrow of

vertebrae, sternum, ribs, and ilia.

• Even in these bones, becomes less productive as age

increases.
• Relative rates of RBC production in marrow of different bones
at different ages.
• Stages of Differentiation of Red Blood Cells

• Proerythroblast is the first cell to be identified as

belonging to RBC series.

• It divides multiple times to form the first-generation

cells called basophil erythroblasts with little
hemoglobin.

• They stain with basic dyes.

• In the successive stage of Polychromatophil

erythroblast and Orthochromatic erythroblast they
accumulate ≈34% hemoglobin.
• As endoplasmic reticulum is reabsorbed they become
reticulocyte.

• The reticulocyte still contains some basophilic material

like remnants of the Golgi apparatus, mitochondria,
and a few other organelles.

– During reticulocyte stage, the cells pass from the bone

marrow into the blood capillaries by diapedesis

• As remnant of basophilic material disaprears the

reticulocyte mature erythrocyte.

• Concentration of reticulocytes is <1% due to short life

of the reticulocytes
• Genesis of normal RBC
• Regulation of Red Blood Cell Production.

• The total mass circulatin RBC is regulated so that:

• (1) adequate RBC available for sufficient oxygen
transport and
• (2) No excess RBC not to impede blood flow.

• Tissue O2 level is the most essential regulator of

RBC Production.
• Factors which leads to tissue hypoxia like
• Higher altitude
• Lung disease
• Heart failure
• Associated with increased RBC production
• Tissue hypoxia initiate erythropoietin secretion from kidney
cells.

• Erythropoietin is a glycoprotein with Mwt of 34,000 which

stimulates RBC Production,

• In the absence of erythropoietin, hypoxia alon has little or no

effect of stimulating RBC production.

• But when the erythropoietin system is functional, hypoxia

causes a marked increase of erythropoietin.

• Then erythropoietin in turn enhances RBC production until the

hypoxia is relieved.

• Erythropoietin secretion is:

– 90 % from kidney
– 10% from liver
• Function of the erythropoietin to increase RBC production
• Effect of Erythropoietin in Erythrogenesis.

• If a person become hypoxic, erythropoietin formed within

minutes to hours, and reaches maximum production within 24
hours.

• But no new RBC appear in the circulating blood until about 5

days later.

• This show that effect of erythropoietin is to stimulate the

production of proerythroblasts from stem cells.

• In addition, once the proerythroblasts are formed, the

erythropoietin causes these cells to pass more rapidly through
the different erythroblastic stages.
• Role of Vitamin B12 (Cyanocobalamin) and
Folic Acid.
• Both vitamin B12 and folic acid are essential
for DNA synthesis b/c required in the formation
of thymidine triphosphate unit of DNA.
• Therefore, lack of either vitamin B12 or folic
acid causes
• abnormal and diminished DNA
• failure of nuclear maturation and cell division
• Failure of erythroblast to proliferate rapidly
• irregular, large, and oval RBC with fragile
membrne.
• Absorption of Vitamin B12 and Pernicious Anemia
• The parietal cells of the gastric glands secrete a glycoprotein
called intrinsic factor, which combines with vitamin B12 in food
and makes the B12 available for absorption

– (1) Intrinsic factor binds to vitamin B12 and protect it from being digested
– (2) bound state of intrinsic factor binds with specific receptor on mucosal
cells in ileum.
– (3) Thus, vitamin B12 is transported into the blood by pinocytosis with
intrinsic factor

• Then vitamin B12 first stored in large quantities in the liver, then
released slowly as needed by the bone marrow.

• only 1 to 3 μg vit B12 required each day to maintain normal RBC

maturation

• Lack of intrinsic factor, causes diminished availability of vitamin

B12 because of faulty absorption of the vitamin.
• Atrophic gastric mucosa that fails to produce
normal gastric secretions impairs vitamin B12
absorption and disease pernicious anemia.
• Formation of Hemoglobin
• Synthesis of hemoglobin begins in the proerythroblasts and
continues even in the reticulocyte stage of RBC.

• First, succinyl-CoA, formed in the Krebs metabolic cycle binds

with glycine to form a pyrrole molecule.

• Four pyrroles combine to form protoporphyrin-IX, which

combines with iron to form the heme molecule.

• Finally, each heme molecule combines with a long polypeptide

chain (globin) synthesized by ribosomes,
• Each hemoglobin chain has a Mwt of ≈16,000;

• Four of these chain bind together loosely to form the whole

hemoglobin.
• Formation of Hemoglobin.
• There are alpha, beta, gamma, and delta hemoglobin chains,
depending on the amino acid composition of the polypeptide
(globin).

• Hemoglobin-A :
– most common hemoglobin in the adult human.
– composed of two alpha and two beta chains.
– has a molecular weight of 64,458.

• The types of hemoglobin chains determine affinity of the

hemoglobin for oxygen.
•
• Abnormalities of the chains alters characteristics of the
hemoglobin.

• Eg. In sickle cell anemia, the amino acid valine is substituted for
glutamic acid
• Oxygen binds with iron of hemoglobin, thus each hemoglobin
can carry 4oxygen.

• Iron Metabolism
• Iron is important for the formation of
– hemoglobin
– myoglobin,
– cytochromes,
– Cytochrome oxidase,
– peroxidase, and
– catalase.
• The quantity of iron in the body averages 4 to 5grams.

• 15% to 30% of iron stored, mainly in the reticuloendothelial

system and liver parenchymal cells in the form of ferritin for
later use.
• Iron absorbed from the small intestine, immediately combines
with beta globulin, apotransferrin in plasma to form transferrin,
which transport iron in plasma.

• The iron is loosely bound in the transferrin and, consequently,

released to any tissue cell at any point in the body.

• Excess iron in the blood is deposited mainly in the hepatocytes

and less in reticuloendothelial cells of the bone marrow.

• This iron stored as ferritin is called storage iron.

• Daily Loss of Iron is ≈ 0.6 mg/day mainly in feces.

• Additionaly iron are lost in bleeding.
• Menstrual flow  iron loss to ≈1.3 mg/day.
• Destruction of Hemoglobin.

• When RBC burst and release their hemoglobin, the

hemoglobin is phagocytized by macrophages
especially in the Kupffer cells of the liver and
macrophages of the spleen and bone marrow.

• The macrophages release iron from the hemoglobin

and back into the blood, to be carried by transferrin.

• macrophages convert porphyrin portion of Hb into the

bile pigment bilirubin, which is released into the blood
and later removed from the body by secretion through
the liver into the bile.
• Anemias
• It is deficiency of hemoglobin in the blood,
caused by either too few red blood cells or too
little hemoglobin in the cells.

• Some types of anemia :

– Blood Loss Anemia (hemorrhage)
– Aplastic Anemia
– Renal Anemia
– Megaloblastic Anemia
– Hemolytic Anemia.
– hereditary spherocytosis,
– sickle cell anemia,
– erythroblastosis fetalis.
• Polycythemia:-excess circulating RBC

• Secondary Polycythemia (physiologic polycythemia)

– rises to RBC count 6 to 7 million/mm3.
– Following hypoxia in higher altitude.

• Polycythemia Vera (Erythremia).

– pathological condition
– RBC count raise 7 to 8 million/mm3 and
– hematocrit reaches 60 to 70%
– caused by a genetic defect in the hemocytoblastic

• Polycythemia leads to :-
 blood viscosity,
• resistance to blood flow,
• blood flow,
• oxygen deliver to the tissue
• Blood Types
• Classifying peoples blood based on antigen on surface of RBC
and naturally occurring antibodies in plasma.

• In the first attempted transfusions, immediate or delayed

agglutination & hemolysis of RBC often occurred, resulting in
typical transfusion reactions that frequently led to death.

• This lead to discover that blood of different people have different

antigenic and immune properties.

• About 30 commonly occurring antigens and hundreds of rare

antigens on RBC are responsible for transfusion reaction

• Two particular types of antigens more likely cause blood

transfusion reactions are:-
• the O-A-B system of antigens and
• the Rh system.
• O-A-B Blood Types

• Two antigens—type A and type B—occur on the RBC surfaces

in a large proportion of human beings.

• These antigens also called agglutinogens b/c they cause blood

cell agglutination-blood transfusion reactions.

• People may have neither of them on their cells, they may have
one, or they may have both of these antigen simultaneously.

• Major O-A-B Blood Types normally classified into four major

O-A-B blood types.

• Two genes, one on each of two paired chromosomes,

determine the O-A-B blood type.
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• Relative Frequencies of the Different Blood Types.
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