What is Blood ????

The body’s only fluid tissue.

❖ Has both cellular and
liquid components.
❖Highly specialized
connective tissue composed
of formed elements
suspended in fluid matrix
called plasma.
Why Blood is called tissue?
Why is it a connective tissue?
What can do blood in a living body?????
Components of Blood
lood Plasma and its components
When all the blood cells—red blood cells, white blood cells, and
platelets—are separated from whole blood, the remaining
straw-colored fluid is blood plasma.
Important constituents include-
Water-
90-92% Water

Plasma proteins- (6–8%)

The three major plasma proteins are Albumin, globulin and Fibrinog
 Albumin – 55.2%
 α1-Globulin – 5.3% (α1-Antitrypsin, TBG-thyroxin binding globulin,
transcortin-corticosteroid binding globulin, etc)
 α2-Globulin – 8.6% (Haptoglobulin, ceruloplasmin, α2- macroglobuli
 β-Globulin – 13.4% (β1-transferin, β-lipoprotein, etc)
 γ-Globulin – 11.0% (Antibodies, etc)
 Fibrinogen – 6.5%
Electrolytes-

Ion Conc (m.Equ.L-1)

Na+ 135–145
K+ 3.6–5.1
Cl- 95–105
Ca2+ 2.0

Trace elements

amino acids, vitamins, organic acids, pigments, and

enzymes. Hormones such as insulin, corticosteroids,
and thyroxine etc.
Biological functions of plasma

 Plasma serves as a transport medium for delivering nutrients

to the cells of the various organs of the body and for
transporting waste products derived from cellular
metabolism to the kidneys, liver, and lungs for excretion.
 It is also a transport system for blood cells, and it plays a
critical role in maintaining normal blood pressure. Plasma
helps to distribute heat throughout the body and to maintain
homeostasis, or biological stability, including acid-base
balance in the blood and body.
 Why chronic liver diseases impair plasma protein levels ???
Plasma proteins
 Biological functions of plasma
proteins

Protein Nutrition: Plasma proteins act as a source of protein for

the tissues, whenever the need arises.
Osmotic Pressure and water balance: Plasma proteins exert
an osmotic pressure of about 25 mm of Hg and therefore play an
important role in maintaining a proper water balance between the
tissues and blood. Plasma albumin is mainly responsible for this
function due to its low molecular weight and quantitative
dominance over other proteins. During the condition of protein
loss from the body as occurs in kidney diseases, excessive amount
of water moves to the tissues producing edema.
What is the relationship between plasma proteins and tissue edema?
Buffering action: Plasma proteins help in maintaining the
pH of the body by acting as ampholytes. At normal blood pH
they act as acids and accept cations.

Transport of Lipids: One of the most important functions of

plasma proteins is to transport lipids and lipid soluble
substances in the body. Fatty acids and bilirubin are
transported mainly by albumin, whereas cholesterol and
phospholipids are carried by the lipoproteins present in β-
globulins also transport fat soluble vitamins (A, D, K and E)
Transport of other substances: In addition to lipids,
plasma proteins also transport several metals and other
substances α2-Globulins transport copper (Ceruloplasmin),
bound hemoglobin (haptoglobin) and thyroxine
(glycoprotein) and non-heme iron is transported by
transferrin present in β-globulin fraction. Calcium,
Magnesium, some drugs and dyes and several cations and
anions are transported by plasma albumin.
Blood Coagulation: Prothrombin present in α2-globulin
fraction and fibrinogen, participate in the blood clotting
process.
 Blood forming cells

1. Red blood cells

(Erythrocytes)
2. White blood cells
(Leukocytes)
a.Granulocytes-
Neutrophils, Eosinophils,
Basophils
b.Agranulocytes-
Monocytes, lymphocytes.
3. Platelets (Thrombocytes)
RBC has no mitochondria and
nucleus, thus It doesn't not
consume oxygen.
omparison among RBCs, WBCs and Platelets
Features RBCs WBCs Platelets

Name Erythrocytes Leucocytes Thrombocytes

Color Red Colorless Purple

Formation Liver and spleen (embryonic life), Red bone marrow and Red bone marrow
red bone marrow of sternum, lymphatic system
ribs, vertebrae (adult life)

Size 6-8 μm Larger than Red Blood 2-4 μm

Cells, 12 to 15 µm
Shape Biconcave Different Plate like

Number per 5-5.5 million (M), 4-4.5 million (F) 4000-11000 150,000 -250,000
mm3 of Blood
Structure Elastic cell membrane, no Have Nucleus No nucleus,
nucleus membrane bounded,
Cytoplasmic
fragments of cells
Life Span 4 months (120 days) Variable (usually 4 8 to 9 days.
months)

Function Transport of Gases Immunity Blood Clotting

Blood Coagulation

Coagulation is a complex process by which the

blood forms clots to block and then heal a
lesion/wound/cut and stop the bleeding. It is a
crucial part of hemostasis - stopping blood
loss from damaged blood vessels. In
hemostasis a damaged blood vessel wall is
plugged by a platelet and a fibrin-containing
clot to stop the bleeding, so that the damage
can be repaired.
Hemostasis –
stopping blood loss from
damaged blood vessels

What is fibrin?
Fibrin is an insoluble protein
involved in blood clotting. Fibrin
is deposited around the wound
in a form of mesh to strengthen
the platelet plug.

Hemostasis
Factors of Blood coagulation

Factor Name
I Fibrinogen
II Prothrombin
III Tissue factor or thromboplastin
IV Calcium
V Proaccelerin (Labile factor)
VII Proconvertin (Stable factor)
VIII Antihaemophilic factor A, Antihaemophilic globulin
Antihaemophilic factor B,
IX
Plasma thromboplastin component, Christmas factor
X Stuart-Prower factor
XI Plasma thromboplastin antecedent, Haemophilia C
XII Hageman factor
XIII Fibrin stabilising factor, Laki-Lorand factor
Pathway of Blood coagulation
 Blood Transfusion

Blood transfusion is the process of

receiving blood or blood products into one's
circulation intravenously.

Transfusions are used for various medical conditions to

replace lost components of the blood. Early transfusions
used whole blood, but modern medical practice
commonly uses only components of the blood, such as
RBCs, WBCs, plasma, clotting factors, and platelets.
Why Would You Need a Blood Transfusion?

 After major surgery or a serious injury need to

replace lost blood
 Excess bleeding in digestive tract from an
ulcer or other condition
 Have an illness like leukemia or kidney
disease that causes anemia
 Received cancer treatments like radiation or
chemotherapy
 Have a blood disorder or severe liver
problems
Types of blood transfusions

There are several common kinds of blood cell

transfusions:
 A red blood cell transfusion may be used if there is
anemia or an iron deficiency.
 A platelet transfusion is used if your body doesn’t
have enough of them, possibly because of cancer or
cancer treatments.
 A plasma transfusion helps replace the proteins in
your blood that help it clot. It may be needed after
severe bleeding or if you have liver disease.
 Risks and complications
 Fever
 Allergic reactions
 Acute immune hemolytic reaction
 Delayed hemolytic reaction
 Anaphylactic reaction
 Transfusion-related acute lung injury
(TRALI)
 Bloodborne Infections
 HIV
 Hepatitis B and C
 West Nile virus
 Zika virus
 Hemochromatosis
 Graft-versus-host disease
 What would do before
transfusion

i) Compatibility testing/ Cross matching

Testing of blood borne infection

 HIV
 Hepatitis B and C
 West Nile virus
 Zika virus
 Hemochromatosis
 Graft-versus-host disease
 What happened after transfusing blood to a
close relative?

Blood transfusion among first degree relatives rarely

results transfusion-associated graft-versus-host disease
(TA-GVHD), which is a devastating one, usually leading to
fatal complication of blood transfusion that results from
the engraftment and clonal expansion of allogenic donor
lymphocytes. TA-GVHD first reported in
immunocompromised patients and later was described
even in immunocompetent hosts following transfusion
when the donor was a first-degree relative. First degree
relatives include parents, offspring, and siblings.
 Blood Group System

1. ABO blood group system

The ABO blood group system involves-

two antigens -- (A & B)
two antibodies (α & β)
found in human blood. The antigens are present on the red
blood cells and the antibodies in the serum. Regarding the
antigen property of the blood all human beings can be
classified into 4 groups,

i) Group A iii) Group AB

ii) Group B iv) Group O

ABO blood group system
The antibodies present together with the antigens are found
as follows:
1. Antigen A with antibody B
2. Antigen B with antibody A
3. Antigen AB has no antibodies
4. Antigen nil (group O) with antibody A and B.
There is an agglutination reaction between similar antigen
and antibody (for example, antigen A agglutinates the
antibody A and antigen B agglutinates the antibody B). Thus,
transfusion can be considered safe as long as the serum of
the recipient does not contain antibodies for the blood cell
antigens of the donor.
The ABO system was invented by Karl Landsteiner in 1901.
 2. Rh blood group system

The Rh system (Rh meaning Rhesus) is the second most

significant blood-group system in human-blood
transfusion with currently 50 antigens. The most
significant Rh antigen is the D antigen

The presence or absence of the Rh(D) antigen is

signified by the + or − sign, so that, for example, the
A+ group is ABO type A and has the Rh (D)
antigen.
gative mother is a risky mother- explain

When a mother is Rh negative and her fetus is

Rh positive, there can be health risks for that
fetus and for the fetus of any subsequent
pregnancies she may have.

1. If the mother is Rh negative and

the father is Rh positive, their fetus
may be Rh positive or Rh negative.
2. If the fetus is Rh positive, there is a risk
that some of its Rh positive blood cells will
get into the mother's bloodstream during
the pregnancy or delivery and mix with
her Rh negative blood.

3. Left untreated, the mother’s blood will

make antibodies that attack the Rh
positive blood of the fetus. These
antibodies can cause health problems for the
fetus, such as anaemia or even death.
5. If the mother then has another baby
later on that is also Rh positive, her
antibodies may cross the placenta and
attack the baby's blood, destroying its
blood cells.
The condition is called hemolytic
disease of newborn (HDN)/
What can be done?
erythroblastosis fetalis
Fortunately, an injection of serum can be given
which stops the mother producing the antibodies
that attack Rh positive blood. This injection is known
as anti-D and contains anti-D gammaglobulin.
Rh incompatibility usually isn't a problem if it's the
mother's first pregnancy because, unless there's
some sort of abnormality, the fetus's blood does not
normally enter the mother's circulatory system
during the course of the pregnancy.
However, during delivery, the mother's and baby's
blood can intermingle. If this happens, the mother's
body recognizes the Rh protein as a foreign
substance and might begin making antibodies
(protein molecules in the immune system that
recognize, and later work to destroy, foreign
Type O blood - universal donors
Type O negative blood is safe for just about everyone. People with
type O negative blood are referred to as universal donors; and type O
negative blood is used for emergencies in which there is no time to
test a person's blood type.
Type AB blood - universal recipients
Individuals who have type AB positive blood are referred to as
universal recipients. This means that they can receive any type of
blood.

Rh-positive and Rh-negative

People who have Rh-positive blood can receive Rh-positive or Rh-
negative blood. If a person has Rh-negative blood, they should only
receive Rh-negative blood. Rh-negative blood is used for emergencies
when there is not time to test a person's Rh type.
Hemolysis

Hemolysis is the rupturing (lysis) of red blood cells

(erythrocytes) and the release of their contents
(cytoplasm) into surrounding fluid (e.g. blood
plasma). Hemolysis may occur in vivo or in vitro
(inside or outside the body).
Conditions that can cause hemolysis
include:
 Immune reactions
 Infections
 Medicines
 Toxins and poisons- Paxillus Involutus
(poisonous mushroom) ingestion can cause
Hemolysis.
 Treatments such as hemodialysis or the use
of the heart-lung bypass machine
Cause of Hemolysis

Inside the body

Hemolysis inside the body can be caused by a large number of

medical conditions, including-
 many Gram-positive bacteria (e.g., Streptococcus, Enterococcus,
and Staphylococcus),
 some parasites (e.g., Plasmodium),
 some autoimmune disorders (e.g., drug-induced hemolytic
anemia),
 some genetic disorders (e.g., Sickle-cell disease or G6PD
deficiency), or blood with too low a solute concentration
(hypotonic to cells).
Hemolysis can lead to hemoglobinemia due to hemoglobin released into
the blood plasma.
Outside the body
In vitro hemolysis can be caused by improper technique
during collection of blood specimens, by the effects of
mechanical processing of blood, or by bacterial action
in cultured blood specimens.
ythrocyte sedimentation rate (ESR

The distance in which RBC fall in 1Hr

The erythrocyte sedimentation rate (ESR)
is the rate at which red blood cells
sediment in a period of one hour. It is a
common hematology test, and is a non-
specific measure of inflammation. To
perform the test, anticoagulated blood was
traditionally placed in an upright tube,
ESR
known as a Westergren tube, and the rate
at which the red blood cells fall was
measured and reported in mm at the end
of one hour.
Mechanism of ESR

There are 3 stages in erythrocyte sedimentation:

Stage 1
Rouleaux formation- Rouleaux (singular is rouleau)
are stacks or aggregations of red blood cells (RBCs)
which form because of the unique discoid shape of the
cells in vertebrates.

Rouleaux effect
Stage 2 :
Sedimentation or settling stage
Stage 3 :
Packing stage - 10 minutes (sedimentation slows and cells
start to pack at the bottom of the tube)

In normal conditions, the RBCs are negatively charged.

Therefore, negatively charged RBCs repel each other and
do not stack over each other. Besides, if the viscosity of
blood is high, RBCs would be slow to fall to the base, thus
lowering the ESR.
Normal Value of ESR

Normal Value Westergreen Wintrobes

Mm in 1st hour Mm in 1st hour
Male 0-7 0-12
Female 0-9 0-20

Any ESR value greater than 20 mm in 1st hour in Westergreen

method is regarded as abnormal

Infection and inflammation increase plasma proteins that alternatively increase ESR.
Factors affecting ESR

The ESR is increased in-

 inflammation,
 pregnancy,
 anemia,
 autoimmune disorders (such as rheumatoid
arthritis and lupus),
 infections,
 some kidney diseases and
 some cancers (such as lymphoma and
multiple myeloma).
The ESR is decreased in
 polycythemia,
 hyperviscosity,
 sickle cell anemia
 leukemia,
 low plasma protein (due to liver or kidney disease)
and
 congestive heart failure
 Medical uses

i) Diagnosis
ESR can sometimes be useful in diagnosing diseases,
such as multiple myeloma, temporal arteritis,
polymyalgia rheumatica, various auto-immune
diseases, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease and chronic
kidney diseases. In many of these cases, the ESR may
exceed 100 mm/hour.
ii) To know the severity of Disease
iii) Monitoring response to therapy
 Functions

 It carries Hb

 Exchange of respiratory gas (O2 and CO2)

 Maintain normal acid-base balance

Erythropoiesis

Erythropoiesis (from Greek 'erythro' meaning "red"

and 'poiesis' meaning "to make") is the process which
produces red blood cells (erythrocytes). It is stimulated
by decreased O2 in circulation, which is detected by
the kidneys, which then secrete the hormone
erythropoietin. This hormone stimulates proliferation
and differentiation of red cell precursors, which
activates increased erythropoiesis in the hemopoietic
tissues, ultimately producing red blood cells
(erythrocytes). In humans, this usually occurs within
the red bone marrow.
Erythropoiesis
Sites of erythropoiesis

Early weeks of embryonic

life-
-Yolk sac
Middle trimester
-Liver
-spleen
Last month of gestation
and after birth
-Red bone marrow, liver and
spleen
Erythrocyte differentiation and maturation
In the process of RBC maturation, a cell undergoes a series of
differentiations. The following stages of development all occur within
the bone marrow:

1. A hemocytoblast--- a multipotent hematopoietic stem cell,

becomes a common myeloid progenitor or a multipotent stem
cell, and then a unipotent stem cell, then
2. A pronormoblast, also commonly called an proerythroblast
3. Then becomes a basophilic or early normoblast, also commonly
called an erythroblast, then
4. a polychromatophilic or intermediate normoblast
5. Then an orthochromatic or late normoblast. At this stage the
nucleus is expelled.
6. Finally the cell becomes a reticulocyte.
7. Mature erythrocyte

The cell is released from the bone marrow as reticulocyte.

In newly circulating red blood cells there are about 1%
reticulocytes. After one to two days, these ultimately
become "erythrocytes" or mature red blood cells.
Erythropoiesis

CFU-E Multipoten
t stem cell
 Eryptosis

The aging red blood cell undergoes changes in its plasma

membrane, making it susceptible to selective recognition
by macrophages and subsequent phagocytosis in the
mononuclear phagocyte system (spleen, liver and lymph
nodes), thus removing old and defective cells and
continually purging the blood. This process is termed
eryptosis, red blood cell programmed cell death. This
process normally occurs at the same rate of production by
erythropoiesis, balancing the total circulating red blood
cell count.
Eryptosis is increased in a wide variety of
diseases including
 sepsis,
 haemolytic uremic syndrome,
 malaria, sickle cell anemia,
 beta-thalassemia,
 glucose-6-phosphate dehydrogenase deficiency,
phosphate depletion,
 iron deficiency and
 Wilson's disease (Cupper accumulated in liver
and brain).
 Anemia

Anemia is a decrease in the total amount of red blood

cells (RBCs) or hemoglobin in the blood, or a lowered
ability of the blood to carry oxygen

Common symptoms of
Anemia
When anemia comes on slowly, the symptoms include feeling
tired, weakness, shortness of breath or a poor ability to
exercise. Anemia that comes on quickly often has greater
symptoms, which may include confusion, feeling like one is
going to pass out, loss of consciousness, or increased thirst.
 Types
The threeof Anemia
main types of anemia are due to-
a) Impaired production-
Disturbance of proliferation and differentiation of stem
cells
 Aplastic anemia affects all kinds of blood cells.
 Anemia of renal failure by insufficient erythropoietin
production
 Anemia of endocrine disorders
Disturbance of proliferation and maturation of
erythroblasts
 Pernicious anemia/ megaloblastic anemia due to vitamin

B12 and folic acid deficiency.

 Anemia of prematurity, by diminished erythropoietin response to
declining hematocrit levels
 Iron deficiency anemia, resulting in deficient heme synthesis
 b) Increased
destruction

i) Hemolytic anemias- Anemias of increased red

blood cell destruction.
ii) Sickle cell anemia- Due to Hemoglobinopathies

c) Blood loss

Causes of blood loss include trauma and

gastrointestinal bleeding, resulting Iron deficiency
anemia
It can also be classified based on the size of red
blood cells and amount of hemoglobin in each cell
i) Microcytic anemia- If the cells are small, it is microcytic
anemia.
ii) Macrocytic anemia- If they are large, it is macrocytic anemia.
iii) Normocytic anemia- If they are normal sized but amount of
Hb is low, it is normocytic anemia. Diagnosis in men is based on
a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL), while
in women; it must be less than 120 to 130 g/L (12 to 13 g/dL).
In conclusion, anemia can be typed as-

 Aplastic anemia
 Pernicious anemia
 Megaloblastic anemia
 Iron deficiency anemia
 Hemolytic anemia
 Sickle cell anemia
 Microcytic anemia
 Macrocytic anemia
 Normocytic anemia
Iron deficiency anemia

The commonest cause of anemia is iron deficiency anemia worldwide.

Cause:
 Blood loss from any reason

 Increased demand such as during growth and pregnancy

 Poor dietary intake

Clinical features

 Brittle nails

 Spoon shape ted nails

 Atrophy (degeneration) of the papillae of the tongue

 Angular stomatitis (inflammation of mouth and lips)

 Brittle hair
Investigation

 Blood count and peripheral blood film examination

 Hb content estimation

 Serum iron and iron binding capacity estimation

 Serum ferritin estimation

Treatment
 Give iron to correct the anemia and replace stores
 Find and treat the underlying cause

The best oral iron preparation is ferrous sulfate (600 mg daily,

containing 120 mg ferrous iron)
 WHO's Hemoglobin thresholds used to define anemia
(1 g/dL = 0.6206 mmol/L)

Age or gender Hb threshold

Hb threshold (g/dl)
group (mmol/l)
Children (0.5–5.0 yrs) 11.0 6.8
Children (5–12 yrs) 11.5 7.1
Teens (12–15 yrs) 12.0 7.4

Women, non-pregnant
12.0 7.4
(>15yrs)

Women, pregnant 11.0 6.8

Men (>15yrs) 13.0 8.1
What is MCH?
MCH stands for mean corpuscular hemoglobin. MCH levels
refer to the average amount of hemoglobin found in the red
blood cells in the body. . Individuals with anemia and a
corresponding low MCHC are said to be hypochromic anemia.
The MCH should be 27 to 33 picograms per cell.

What is MCV?

Mean corpuscular volume (MCV), which is the average red

blood cell size. The MCV should be 80 to 96 femtoliters. Low
MCV indicates microcytic, normal MCV indicates normocytic
and high MCV indicates macrocytic anemia.
Megaloblastic anemia

Megaloblastic anemia is characterized by the presence

in the bone marrow of erythroblast with delayed
nuclear maturation because of defective DNA synthesis

Cause of megaloblastic anemia

 Vitamin B12 deficiencies or abnormal Vitamin B12
metabolism
 Folic acid deficiencies or abnormal folic acid metabolism
 Other defects of DNA synthesis e,g,. Congenital enzyme
deficiences in DNA synthesis
Clinical Features Investigations

 Anemia
 Blood count
 Mild jaundice
 Hb content (6-8 gm/dl)
 Bone pain
 A high reticulocyte count
 Chest pain
 Blood film: Sickling of red
 Hematuria
cells on a blood film.
 Chronic leg ulcer due to
ischemia
 Susceptibility to infection
 Blindness
 Chronic renal failure

In megaloblastic anemia MCV is greater than 96 fl

Thalassemia

Thalassemia is an inherited blood disorder in which the

body makes an abnormal form of hemoglobin. The disorder
results in excessive destruction of red blood cells, which
leads to anemia. Thalassemia is inherited, meaning that at
least one of one’s parents must be a carrier of the disease.

There are two main forms of thalassemia-

 alpha thalassemia- in which at least one of the alpha
globin genes has a mutation or abnormality.
 beta thalassemia, the beta globin genes are affected.
Hemoglobin structure
 Assignment

 Classification, characteristic features and biological

functions of WBC.
 In which conditions WBC counts would be increased or
decreased?
 How are platelets produced?

 What are the three major functions of platelets?

 What are the clinical manifestations of either increased or

decreased platelet levels? What are the factors affecting
platelet levels?
 Why complete blood count (CBC) is essential to diagnose
diseases ?
 List the diseases that can be diagnosed from CBC.