Medical physiology Lec 3

Blood physiology
Blood: is a connective tissue in fluid form. It is considered as the fluid of
life because it carries oxygen from lungs to all parts of the body and carbon
dioxide from all parts of the body to the lungs.

PROPERTIES OF BLOOD

1. Color: Blood is red in color. Arterial blood is scarlet red because of

more O2 and venous blood is purple red because of more CO2.

2. Volume: The average volume of blood in a normal adult is 5 L. In

newborn baby it is 450 ml. It increases during growth and reaches 5 L at
the time of puberty. In females, it is slightly less and is about 4.5 L. It is
about 8% of the body weight in a normal young healthy adult weighing
about 70 kg.

3. Reaction and pH: Blood is slightly alkaline and its pH in normal

conditions is 7.4.

4. Viscosity: Blood is five times more viscous than water. It is mainly due
to red blood cells and plasma protein

Blood is made of two parts:

1-Plasma which makes up 55% of blood volume
2-Formed cellular elements (red and white blood cells, and platelets) which
combine to make the remaining 45% of blood volume.
Functions of the blood include:
1. Nutrient Function
Nutritive substances like glucose, amino acids, lipids and vitamins derived
from digested food are absorbed from gastrointestinal tract and carried by
blood to different parts of the body for growth and production of energy.

2. Respiratory Function
Transport of respiratory gases is done by the blood. It carries O2 from
alveoli of lungs to different tissues and CO2 from tissues to alveoli.

3. Excretory Function
Waste products formed in the tissues during various metabolic activities
are removed by blood and carried to the excretory organs like kidney, skin,
liver, etc. for excretion.

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4. Transport of Hormones and Enzymes

Hormones which are secreted by ductless (endocrine) glands are released
directly into the blood. The blood transports these hormones to their target
organs/tissues. Blood also transports enzymes.

5. Regulation of Acid-base Balance the plasma proteins and hemoglobin

act as buffers and help in regulation of acid-base balance.

6. Regulation of Body Temperature Because of the high specific heat of

blood, it is responsible for maintaining the thermoregulatory mechanism in
the body, i.e. the balance between heat loss and heat gain in the body.

7. Storage Function
Water and some important substances like proteins, glucose, sodium and
potassium are constantly required by the tissues. All these substances are
present in the blood are taken by the tissues during the conditions like
starvation, fluid loss, electrolyte loss, etc.

8. Defensive Function
The WBCs in the blood provide the defense mechanism and protect the
body from the invading organisms. Neutrophils and monocytes engulf the
bacteria by phagocytosis. Lymphocytes provide cellular and humoral
immunity. Eosinophils protect the body by detoxification, disintegration
and removal of foreign proteins.

Plasma
Plasma is a straw-colored clear liquid part of blood. It contains 91 to 92%
of water and 8 to 9% of solids. The solids are the organic and inorganic
substances.

Serum
Serum is the clear straw-colored fluid that oozes out from the clot. When
the blood is shed or collected in a container, it clots because of the
conversion of fibrinogen into fibrin. After about 45 minutes, serum oozes
out of the clot. For clinical investigations, serum is separated from blood
cells by centrifuging. Volume of the serum is almost the same as that of
plasma (55%). It is different from plasma only by the absence of
fibrinogen, i.e., serum contains all the other constituents of plasma except
fibrinogen. Fibrinogen is absent in serum because it is converted into fibrin
during blood clotting. Thus, the Serum = Plasma – Fibrinogen.

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PLASMA PROTEINS
The plasma proteins are:
1. Serum albumin
2. Serum globulin
3. Fibrinogen.
Globulin is of three types,
Α-globulin,
β-globulin and
γ-globulin.

NORMAL VALUES
The normal values of the plasma proteins are:
Total proteins: 7.3 g/dL (6.4-8.3 g/dL)
Serum albumin: 4.7 g/dL
Serum globulin: 2.3 g/dL
Fibrinogen: 0.3 g/d
Albumin/globulin Ratio
The ratio between plasma level of albumin and globulin is called
Albumin/Globulin (A/G) ratio. It is an important indicator of some liver
and kidney diseases. Normal A/G ratio is 2:1.

ORIGIN OF PLASMA PROTEINS

In embryonic stage, the plasma proteins are synthesized by the
mesenchyme cells. In adult s, the plasma proteins are synthesized mainly
from reticuloendothelial cells of liver and also from spleen, bone marrow,
disintegrating blood cells and general tissue cells. Gamma globulin is
synthesized from B lymphocytes.

FUNCTIONS OF PLASMA PROTEINS

1. Role in Coagulation of Blood Fibrinogen is essential for the coagulation
of Blood.
2. Role in Defense Mechanism of Body the gamma globulins play an
important role in the defense mechanism of the body by acting as
antibodies. These proteins are also called immunoglobulins.
3. Role in Transport Mechanism: Plasma proteins are essential for the
transport of various substances in the blood. Albumin, alpha globulin and
beta globulin are responsible for the transport of the hormones, enzymes,
etc.
The alpha and beta globulins transport metals in the blood.

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4. Role in Maintenance of Osmotic: Pressure in Blood Plasma proteins

exert the colloidal osmotic (oncotic) pressure.

5. Role in Regulation of Acid-base Balance: Plasma proteins, particularly

the albumin, play an important role in regulating the acid-base balance in
the blood. This is because of the virtue of their buffering action.

6. Role in Viscosity of Blood: The plasma proteins provide viscosity to the

blood, which is important to maintain the blood pressure. Albumin
provides maximum viscosity than the other plasma proteins.

7. Role in Erythrocyte Sedimentation Rate (ESR): Globulin and fibrinogen

accelerate the tendency of rouleaux formation by the red blood cells.
Rouleaux formation is responsible for ESR, which is an important
diagnostic and prognostic too.

8. Role as Reserve Proteins

During fasting, inadequate food intake or inadequate protein intake, the
plasma proteins are utilized by the body tissues as the last source of energy.
The plasma proteins are split into amino acids by the tissue macrophages.
The amino acids are taken back by blood and distributed throughout the
body to form cellular protein molecules. Because of this, the plasma
proteins are called the reserve proteins.
Red blood cells (RBCs)
Red blood cells (RBCs), also known as erythrocytes are the non-nucleated
formed elements in the blood. The red color of the RBC is due to the
presence of hemoglobin.

NORMAL VALUE
The RBC count ranges between 4 and 5.5 millions/cu mm of blood. In adult
males, it is 5 millions/cu mm and in adult females it is 4.5 millions/cu mm.

MORPHOLOGY OF RED BLOOD CELLS

NORMAL SHAPE
Normally, the RBCs are disk-shaped and biconcave (dumbbell-shaped).
The central portion is thinner and periphery is thicker. The biconcave
contour of RBCs has some mechanical and functional advantages.

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Advantages of Biconcave Shape of RBCs

1. It helps in equal and rapid diffusion of oxygen and other substances into
the interior of the cell.
2. Large surface area is provided for absorption or removal of different
substances.
3. While passing through minute capillaries, RBCs can squeeze through
the capillaries easily without getting damaged.
NORMAL SIZE
Diameter: 7.2 μ (6.9 to 7.4 μ).

Dimensions of RBC. A: Surface Rouleaux formation

view. B. Sectioned view

FUNCTIONS OF RED BLOOD CELLS

1. Transport of O2 from the Lungs to the tissues Hemoglobin combines

with oxygen to form oxyhemoglobin.
2. Transport CO2 from the Tissues to the Lungs Hemoglobin combines
with carbon dioxide and form carbhemoglobin.
3. Buffering Action in Blood: Hemoglobin functions as a good buffer. By
this action, it regulates the hydrogen ion concentration and thereby plays a
role in the maintenance of acid-base balance.
4. In Blood Group Determination: RBCs carry the blood group antigens
like A antigen, B antigen and Rh factor. This helps in determination of
blood group and enables to prevent the reactions due to incompatible blood
transfusion.

Erythropoiesis
Erythropoiesis is the process of the origin, development and maturation of
erythrocytes.
Hemopoiesis is the process of origin, development and maturation of all
the blood cells.

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SITE OF ERYTHROPOIESIS

IN FETAL LIFE
In fetal life, the erythropoiesis occurs in different sites in different periods:

Fetus 0-2 months (yolk sac)

2-7 months (liver, spleen)
5-9 months (bone marrow)

Infants bone marrow (practically all bones)

Stem cells. L – Lymphocyte, R – Red blood cells, N – Neutrophil, B – Basophil, E – Eosinophil, M –

Monocyte, P – Platelets

PROCESS OF ERYTHROPOIESIS

STEM CELLS
RBCs develop from the hemopoietic stem cells in the bone marrow. These
cells are called uncommitted pluripotent hemopoietic stem cells (PHSC).
PHSC are not designed to form a particular type of blood cell; hence the
name uncommitted PHSC. When the cells are designed to form a particular
type of blood cell, the uncommitted PHSCs are called committed.

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The committed PHSCs are of two types:
1. Lymphoid stem cells (LSC) which give rise to lymphocytes and natural
killer (NK) cell
2. Colony forming blastocytes, which give rise to all the other blood cells
except lympho-cytes. When grown in cultures, these cells form colonies
hence the name colony forming blastocytes.

The different units of colony forming cells are:

i. Colony forming Unit – Erythrocytes (CFU-E) from which RBCs
develop.
ii. Colony forming Unit – Granulocytes/Monocytes (CFU-GM) from
which granulocytes (neutrophils, basophils and eosinophils) and
monocytes develop.
iii. Colony forming Unit – Megakaryocytes (CFU-M) from which platelets
develop.

Genesis of RBC

The first cell that can be identified as belonging to the red blood cell series
is the proerythroblast,
under appropriate stimulation, large numbers of these cells are formed
from the CFU-E stem cells. Once the proerythroblast has been formed, it
divides multiple times, eventually forming many mature red blood cells.
The first-generation cells are called basophil erythroblasts because they
stain with basic dyes; the cell at this time has accumulated very little
hemoglobin. In the succeeding generations, the cells become filled with
hemoglobin to a concentration of about 34 per cent, the nucleus condenses
to a small size, and its final remnant is absorbed or extruded from the cell.
At the same time, the endoplasmic reticulum is also reabsorbed. The cell
at this stage is called a reticulocyte because it still contains a small amount
of basophilic material, consisting of remnants of the Golgi apparatus,
mitochondria, and a few other cytoplasmic organelles. During this
reticulocyte stage, the cells pass from the bone marrow into the blood
capillaries by diapedesis (squeezing through the pores of the capillary
membrane). The remaining basophilic material in the reticulocyte normally
disappears within 1 to 2 days, and the cell is then a mature erythrocyte.
Because of the short life of the reticulocytes, their concentration among all
the red cells of the blood is normally slightly less than 1 per cent.

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Genesis of normal red blood cells (RBCs) and characteristics of RBCs in

different types of anemias.

FACTORS NECESSARY FOR ERYTHROPOIESIS

Development and maturation of erythrocytes require many factors which
are classified into 3 categories:
I. General factors
II. Maturation factors
III. Factors necessary for hemoglobin formation.

GENERAL FACTORS

1. Erythropoietin
Erythropoietin is a hormone secreted mainly by peritubular capillaries in
the kidney and a small quantity is also secreted from the liver and the brain.
Hypoxia is the stimulant for the secretion of erythropoietin.
Erythropoietin promotes the following processes:
i. Production of proerythroblasts from CFU-E of the bone marrow.
ii. Development of proerythroblasts into matured RBCs through the several
stages
iii. Release of matured erythrocytes into blood. Some reticulocytes are also
released along with matured RBCs.

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2. Thyroxine
Being a general metabolic hormone, thyroxine accelerates the process of
erythropoiesis at many levels.
3. Hemopoietic Growth Factors Hemopoietic growth factors or growth
inducers are the interleukins – 3, 6 and 11 and stem cell factor (steel factor).
Generally, these factors induce the proliferation of PHSCs.
4. Vitamins
The vitamins A, B, C, D and E are necessary for erythropoiesis. Deficiency
of these vitamins causes anemia.

MATURATION FACTORS

Vitamin B12, intrinsic factor and folic acid are necessary for the maturation
of RBCs.
1. Vitamin B12 (Cyanocobalamin). Vitamin B12 is essential for synthesis
of DNA, cell division and maturation in RBCs. It is also called extrinsic
factor as it is obtained mostly from diet. It is also produced in the large
intestine by the intestinal flora. It is absorbed from the small intestine in
the presence of intrinsic factor of Castle. Vitamin B12
is stored mostly in liver and in small quantity in muscle. Its deficiency
causes pernicious anemia (macrocyticanemia) in which the cells remain
larger with fragile and weak cell membrane.

2. Intrinsic Factor of Castle

It is produced in gastric mucosa by the parietal cells of the gastric glands.
It is essential for the absorption of vitamin B12 from intestine. Absence of
intrinsic factor also leads to pernicious anemia because of failure of vitamin
B12 absorption. The deficiency of intrinsic factor occurs in conditions like
severe gastritis, ulcer and gastrectomy.

3. Folic Acid
Folic acid is also essential for the synthesis of DNA. Deficiency of folic
acid decreases the DNA synthesis causing maturation failure. Here the
cells are larger and remain in megaloblastic (proerythroblastic) stage which
leads to
megaloblastic anemia.

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FACTORS NECESSARY FOR HEMOGLOBIN FORMATION

Various materials are essential for the formation of hemoglobin in the
RBCs such as:
1.First class proteins and amino acids of high biological value — for the
formation of globin.
2.Iron — for the formation of heme part of the hemoglobin.
3.Copper — for the absorption of iron from GI tract.
4.Cobalt and nickel — for the utilization of iron during hemoglobin
synthesis.
5.Vitamins: Vitamin C, riboflavin, nicotinic acid and pyridoxine — for
hemoglobin synthesis.

LIFE SPAN OF RED BLOOD CELLS

Average lifespan of RBC is about 120 days. After the lifetime, the senile
(old) RBCs are destroyed in reticuloendothelial system.

FATE OF RED BLOOD CELLS

When the RBCs become older (120 days), the cell membrane becomes very
fragile. So, these cells are destroyed while trying to squeeze through the
capillaries which have lesser or equal diameter as that of RBC. The
destruction occurs mainly in the capillaries of spleen because these
capillaries are very much narrow. So, the spleen is called graveyard of
RBCs. The destroyed RBCs are fragmented and hemoglobin is released
from the fragmented parts. Hemoglobin is degraded into iron, globin and
porphyrin. Iron combines with the protein called apoferritin to form
ferritin, which is stored in the body and reused later. Globin enters the
protein depot for later use .The porphyrin is degraded into bilirubin which
is excreted by liver through bile. Daily 10% of senile RBCs are destroyed
in normal young healthy adults. It causes release of about 0.6 g/dL of
hemoglobin into the plasma.
From this 0.9 to 1.5 mg/dL bilirubin is formed.

Fate of RBC
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PROPERTIES OF RED BLOOD CELLS

1. ROULEAUX FORMATION
When blood is taken out of the blood vessel, the RBCs pile up one above
another like the pile of coins.
This property of the RBCs is called rouleaux (pleural = rouleau) formation.
It is accelerated by plasma proteins, namely globulin and fibrinogen.

2. SPECIFIC GRAVITY
The specific gravity of RBC is 1.092 to 1.101.

3. PACKED CELL VOLUME

Packed cell volume (PCV) is the volume of the RBSc expressed in percent
age. It is also called hematocrit value. It is 45% of the blood and the plasma
volume is 55% .

4. SUSPENSION STABILITY: During circulation, the RBCs remain

suspended or dispersed uniformly in the blood. This property of the RBCs
is called the suspension stability.

VARIATIONS IN NUMBER OF RED BLOOD CELLS

PHYSIOLOGICAL VARIATIONS

A-Increase in RBC Count — Polycythemia:

Increase in the RBC count is known as polycythemia. It occurs in both
physiological and pathological conditions. When it occurs in physiological
conditions it is called physiological polycythemia. The increase in number
during this condition is marginal and temporary. It occurs in the following
conditions:

1. Age
At birth, the RBC count is 8 to 10 millions/cu mm of blood. The count
decreases within 10 days after birth due to destruction of RBCs. This may
cause physiological jaundice in some newborn babies. In infants and
growing children, the RBC count is more than in the adults.

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2. Sex
Before puberty and after menopause, in females the RBC count is similar
to that in males. During reproductive period of females, the count is less
than that of males (4.5 millions/cu mm).

3. High altitude
In people living in mountains (above 10,000 feet from mean sea level), the
RBC count is more than 7 millions/cu mm. It is due to hypoxia (decreased
oxygen supply to tissues) in high altitude. Hypoxia stimulates kidney to
secrete a hormone called erythropoietin which stimulates the bone marrow
to produce more RBCs.

Physiological polycythemia in high altitude

4. Muscular exercise
RBC count increases after muscular exercise. It is because of mild hypoxia
which increases the sympathetic activity and secretion of adrenaline from
adrenal medulla. Adrenaline contracts spleen and RBCs are released into
blood. Hypoxia causes secretion of erythropoietin which stimulates the
bone marrow to produce more RBCs.
5. Emotional Conditions
The RBC count increases during the emotional conditions such as anxiety.
It is because of increase in the sympathetic activity and contraction of
spleen .

RBC count in emotional conditio

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6. Increased environmental temperature generally increased temperature

increases all the activities in the body including production of RBCs.

7. After meals
There is a slight increase in the RBC count after taking meals. It is because
of need for more oxygen for metabolic activities.

Pathological Polycythemia

Pathological polycythemia is the abnormal increase in the RBC count. The

count increases above 7 millions/cu mm of the blood. Polycythemia is of
two types, the primary polycythemia and secondary polycythemia.
Primary Polycythemia — Polycythemia Vera Primary polycythemia is
otherwise known as polycythemia vera. It is a disease characterized by
persistent increase in RBC count above 14 millions/cu mm of blood. This
is always associated with increased WBC count above 24,000/cu mm of
blood. Polycythemia vera occurs because of red bone marrow malignancy.

Secondary Polycythemia

It is the pathological condition in which poly-cythemia occurs because of

diseases in some other system such as:
1. Respiratory disorders like emphysema
2. Congenital heart disease
3. Ayerza’s disease — condition associated with hypertrophy of right
ventricle and obstruction of blood flow to lungs.
4. Chronic carbon monoxide poisoning.
5. Poisoning by chemicals like phosphorus and arsenic
6. Repeated mild hemorrhages.
All these conditions lead to hypoxia which stimulates the release of
erythropoietin.
Erythropoietin stimulates the bone marrow resulting in increased RBC
count.

B. Decrease in RBC Count

Decrease in RBC count occurs in the following physiological conditions:

1. High Barometric Pressures

At high barometric pressures as in deep sea, where the oxygen tension of
blood is higher, the RBC count decreases.

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2. During Sleep
Generally, all the activities of the body are decreased during sleep
including production of RBCs.

3. Pregnancy
In pregnancy, the RBC count decreases. It is because of increase in ECF
volume. Increase in ECF volume, increases the plasma volume also
resulting in hemodilution. So, there is a relative reduction in the RBC
count.

Anemia
The abnormal decrease in RBC count is called anemia.

VARIATIONS IN SIZE OF RED BLOOD CELLS

Under physiological conditions, the size of RBCs in venous blood is

slightly larger than those in arterial blood. In pathological conditions, the
variations in size of RBCs are:

1. Microcytes —smaller cells

2. Macrocytes — larger cells
3. Anisocytosis —cells of different sizes.

Anemia is the blood disorder characterized by the reduction in:

1. Red blood cell count
2. Hemoglobin content
3. Packed cell volume.

CLASSIFICATION OF ANEMIA
Anemia is classified by two methods:
A. Morphological classification
B. Etiological classification.

MORPHOLOGICAL CLASSIFICATION

Morphological classification depends upon the size and color of RBC.

Size of RBC is expressed as mean corpuscular volume (MCV) and the
color is expressed as mean corpuscular hemoglobin concentration
(MCHC). By this method, the anemia is classified into four types as given

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Morphological classification of anemia

ETIOLOGICAL CLASSIFICATION

On the basis of the etiology (study of cause or origin), the anemia is divided
into five types:

1-Hemorrhagic Anemia
Hemorrhage refers to excessive loss of blood anemia due to hemorrhage is
known as hemorrhagic anemia or blood loss anemia. It occurs both in acute
and chronic hemorrhagic conditions.

Acute Hemorrhage
Acute hemorrhage means sudden loss of large quantity of blood as in case
of accidents. The RBCs are normocytic and normochromic.

Chronic Hemorrhage
It refers to loss of blood over a long period of time by internal or external
bleeding as in conditions like peptic ulcer, purpura, hemophilia and
menorrhagia. The RBCs are microcytic and hypochromic . It is because of
decrease in iron content.

2. Hemolytic Anemia
Hemolysis means destruction of RBCs. Anemia due to excessive
destruction of RBCs is called hemolytic anemia. Hemolysis occurs because
of the following reasons:
i. Liver failure
ii. Renal disorder
iii. Hypersplenism
iv. Burns

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v. Infections like hepatitis, malaria and septicemia
vi. Drugs such as penicillin, antimalarial drugs and sulfa drugs
vii. Poisoning by chemical substances like lead, coal and tar
viii. Presence of isoagglutinins like anti-Rh
ix. Autoimmune diseases such as rheumatoid arthritis and ulcerative
colitis.
x. Hereditary factors

Hereditary Disorders
Sickle cell anemia
Sickle cell anemia is an inherited blood disorder characterized by sickle
shaped RBCs. It occurs when a person inherit s two abnormal genes (one
from each parent). It is also called hemoglobin SS disease or sickle cell
disease. It is common in people of African origin.
In sickle cell anemia, hemoglobin becomes abnormal with normal α chains
and abnormal β chains. Because of this, RBCs attain sickle (crescent) shape
and become more fragile leading to hemolysis.
Thalassemia
Thalassemia is an inherited disorder characterized by abnormal
hemoglobin. In normal hemoglobin, the number of α and β chains is equal.
In thalassemia the number of these chains is not equal. This causes the
precipitation of the polypeptide chains leading to defective formation of
RBCs or hemolysis of the matured RBCs.
It is also known as Cooley’s anemia or Mediterranean anemia. It is more
common in Thailand and to some extent in Mediterranean countries.

Thalassemia is of two types:

i. α thalassemia
ii. β thalassemia. The β thalassemia is very common among these two.

3. Nutrition Deficiency Anemia

Anemia that occurs due to deficiency of a nutritive substance necessary for
erythropoiesis is called nutrition deficiency anemia. Such substances are
iron, proteins and vitamins like C, B12 and folic acid. The types of nutrition
deficiency anemia are:

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Iron deficiency anemia

Iron deficiency anemia is the most common type of anemia. It develops
due to inadequate availability of iron for hemoglobin synthesis. The RBCs
are microcytic and hypochromic.

Protein deficiency anemia

Protein deficiency decreases the hemoglobin synthesis and the RBCs
become macrocytic and hypochromic in nature.
Vitamin B12 deficiency — Pernicious anemia Vitamin B12 is a maturation
factor for RBC and deficiency of this causes pernicious anemia which is
also called Addison’s anemia. It occurs because of less intake of vitamin
B12 or poor absorption of vitamin B12. Vitamin B12 is absorbed from the
stomach with the help of intrinsic factor of Castle which is secreted in the
gastric mucosa. Decrease in the production of intrinsic factor causes poor
absorption of vitamin B12.

RBCs are macrocytic and normochromic/hypochromic.

Folic acid deficiency — Megaloblastic anemia

Folic acid is necessary for the maturation of RBC.
Deficiency of this leads to defective DNA synthesis making the nucleus to
remain immature. The RBCs are megaloblastic and hypochromic .

4. Aplastic Anemia
Aplastic anemia is due to the bone marrow disorder. The red bone marrow
is reduced and replaced by fatty tissues. In this condition, the RBCs are
normocytic and normochromic. It occurs in conditions such as repeated
exposure to X-ray or gamma ray radiation, tuberculosis and viral infections
like hepatitis and HIV infections.

5. Anemia due to Chronic Diseases

Anemia occurs due to some chronic diseases such as rheumatoid arthritis,
normochromic.

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Etiological classification of anemia

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