HKMU

Physiology: Blood
First Year

Mpoki Ulisubisya, MD FCA(ECSA)

White blood cells

Platelets

Red blood cells

BLOOD: Outline
• Composition
• Plasma Proteins et Functions
• Red Blood Cells
• Formation
• Characteristics
• Functions
• Destruction
BLOOD
• A connective tissue in fluid form.
• Considered - 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 - more O2
• Venous blood is purple red - 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

pH is 7.35 – 7.45.
Blood is made of two parts:
• Plasma makes up 55% of blood volume

• Formed cellular elements makes up 45% of blood volume:

• Red,
• White Blood Cells,
• Platelets
Functions:

1. Nutrition

Nutritive substances like:

• glucose,
• amino acids,
• lipids
• 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

Transports of respiratory gases:

• Carries O2 from alveoli of lungs to different tissues
• Carries CO2 from tissues to alveoli.
6. Body Temperature Regulation
• Because of the high specific heat of blood,

• it is responsible for maintaining the thermoregulatory

mechanism in the body

• the balance between heat loss and heat gain in the body.
8. Storage Function

• Water and some important substances like proteins, glucose, sodium

and potassium are constantly required by the tissues.
• These substances are present in the blood taken by the tissues in :
• starvation,
• fluid loss,
• electrolyte loss, etc.
9. Defensive Function

• Blood provides 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.

Plasma
• a straw colored clear liquid part of blood.
• contains
• 91 to 92% of water
• 8 to 9% of solids.
• solids are the organic and inorganic substances.
Serum
• 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.
 Plasma-
55%
Buffy coat- <1%

Formed
elements-45%
• Volume of the serum is almost the same as that of
plasma [55%].
• It is different from plasma only by the absence of fibrinogen,
• serum contains all the other constituents of plasma except
fibrinogen.

• Fibrinogen is absent in serum because it is converted into fibrin

during blood clotting.

• Serum = Plasma – Fibrinogen.

PLASMA PROTEINS
The plasma proteins are:
1. Serum albumin
2. Serum globulin
Α-globulin,
β-globulin
γ-globulin
3. Fibrinogen.
• 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 adults,
• the plasma proteins are synthesized mainly from
• reticuloendothelial cells of liver
• 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.
4. Role in Maintenance of Osmotic
Pressure:
• Pressure in Blood Plasma proteins exert the colloidal osmotic (oncotic)
pressure.

• The osmotic pressure exerted by the plasma proteins is about 25 mm Hg.

• the concentration of albumin [is more than the other plasma proteins],
• it exerts maximum pressure.
5. Role in Regulation of Acid-base Balance:

• Particularly the albumin, play an important role in regulating the acid-

base balance in the blood.
• 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,

• an important diagnostic and prognostic too.

 8. 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.
• 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.
• the reserve proteins.
Erythrocytes
NORMAL VALUES

The RBC count ranges between 4 and 5.5 millions/mm3 of blood.

• adult males, it is 5 millions/mm3

• adult females it is 4.5 millions/mm3.

Red blood cells (RBCs)
• also known as erythrocytes
• are the non-nucleated formed elements in the blood.
• The red color is due to the presence of hemoglobin.
MORPHOLOGY OF RED BLOOD CELLS
SHAPE
• they 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.
Advantages of Biconcave Shape of RBCs

• It helps in equal and rapid diffusion of oxygen and other substances

into the interior of the cell.
• Large surface area is provided for absorption or removal of different
substances.
• Allows for easy squeezing while passing through minute capillaries,
without getting damaged.
SIZE
• Diameter: 7.2 μ (6.9 to 7.4 μ).
• Thickness:
• periphery it is thicker with 2.2 μ
• center it is thinner with 1μ.
• The difference in thickness is because of the biconcave shape.

Surface area: 120 sq μ.

Volume: 85 to 90 cu μ.
 STRUCTURE

• RBC is non-nucleated cell.

• DNA is absent.
• Organelles such as mitochondria and Golgi apparatus
also are absent in RBC.
• The energy is produced from glycolitic processes.
PROPERTIES OF RED BLOOD CELLS

1. ROULEAUX FORMATION

• Blood taken out of the blood vessel, the RBCs pile up

one above another like a pile of coins.
• This property of the RBCs is called rouleaux (plural =
rouleau) formation .
• It is accelerated by plasma proteins, namely globulin
and fibrinogen.
2. PACKED CELL VOLUME

• Packed cell volume (PCV) is the volume of the RBC expressed in

percent age.
• Also called hematocrit value.
• It is 45% of the blood, the rest being plasma
LIFE SPAN OF RED BLOOD CELLS

• Average lifespan of RBC is about 120 days.

• The senile (old) RBCs are destroyed in reticuloendothelial system.
FATE OF RED BLOOD CELLS
• When the RBCs become older (120 days), the cell membranebecomes
very fragile.
• 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.
• The spleen is called graveyard of RBCs.
FATE OF RED BLOOD CELLS
• Hemoglobin is released from the fragmented RBCs.
• Hemoglobin is degraded into iron, globin and porphyrin.
• Iron combines with apoferritin[protein] 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.
FATE OF RED BLOOD CELLS
FUNCTIONS OF RED BLOOD CELLS
• Transport of O2 from the Lungs to the tissues
Hemoglobin combines with oxygen to form
oxyhemoglobin.
• Transport CO2 from the Tissues to the Lungs
Hemoglobin combines with carbon dioxide and form
carbhemoglobin.
• Buffering Action in Blood:
• Hemoglobin functions as a buffer, it regulates the hydrogen ion
concentration
• playing a role in the maintenance of acid-base balance.
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.
SITE OF ERYTHROPOIESIS

• In childhood 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)
• Infancy bone marrow (practically all bones)

• After 20 years this function is effected by the membranous bones:

• Skull
• Vertebrae
• Ribs
• Sternum
• scapulas
• Pelvic bones
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 - uncommitted PHSC.
The different units of colony forming
cells are:
• Colony forming Units:
• Erythrocytes (CFU-E) from which Red Blood Cells develop.

• Granulocytes/Monocytes (CFU-GM) from which ganulocytes (neutrophils,

basophils and eosinophils) and monocytes develop.

• Megakaryocytes (CFU-M) from which platelets develop.

STAGES OF ERYTHROPOIESIS

The various stages between CFU-E cells and matured RBC are:
1. Proerythroblast
2. Early normoblast
3. Intermediate normoblast
4. Late normoblast
5. Reticulocyte
6. Matured erythrocyte
1. Proerythroblast (Megaloblast)
• Proerythroblast or megaloblast is very large in size with a diameter of about
20 μ.
• large nucleus with two or more nucleoli and a chromatin network is present.
Hemoglobin is absent.
• The cytoplasm is basophilic in nature.
• The proerythroblast multiplies several times to finally form the early
normoblast.
2. Early Normoblast
• It is smaller than proerythroblast with a diameter of about 15 μ.
• The nucleoli disappear from the nucleus and condensation of
chromatin network occurs.
• The condensed network becomes dense.
• The cytoplasm is basophilic in nature, this cell is also called basophilic
erythroblast.
• Develops into the next stage - intermediate normoblast.
3. Intermediate Normoblast

• It is smaller than the early normoblast with a diameter of 10 to 12 μ.

• The nucleus is still present, the chromatin network shows further
condensation.
• This stage is marked by the appearance of hemoglobin.
• Because of the presence of small quantity of acidic hemoglobin, the
cytoplasm which is basophilic becomes polychromatic, i.e. both acidic and
basic in nature.
• This cell is polychromophilic or polychromatic erythroblast.
• This cell develops into the late normoblast.
4. Late Normoblast
• The diameter of the cell decreases further to about 8 to 10 μ.
• Nucleus becomes very small with very much condensed chromatin network
called ink spot nucleus.
• Quantity of hemoglobin increases making the cytoplasm almost acidophilic.
• the cell is now called orthochromic erythroblast.
• At the end of late normoblastic stage, just before it passes to the next stage,
the nucleus disintegrates and disappears by the process called pyknosis.
• The final remnant is extruded from the cell.
• Late normoblast develops into the next stage called reticulocyte.
 5. Reticulocyte

• It is slightly larger than matured RBC.

• It is known as immature RBC.
• It is called reticulocyte because, the reticular network or reticulum that is
formed from the disintegrated organelles are present in the cytoplasm.
• In newborn babies, the reticulocyte count is 2 to 6% of RBCs,
• 2 to 6 reticulocytes are present for every 100 RBCs.
• The number of reticulocytes decreases during the first week after birth, the
reticulocyte count remains constant at or below 1%.
• The number increases whenever the erythropoietic activity increases.
• Reticulocytes can enter the capillaries through the capillary membrane from
the site of production by diapedesis. [sequeeze through the capillary walls by amoeboid process]
6. Matured Erythrocyte
• The cell decreases in size with the diameter of 7.2 μ.

• The reticular network disappears and the cell becomes the

matured RBC with biconcave shape and hemoglobin but
without nucleus.

• It requires seven days for the proerythroblast to become fully

developed and a matured RBC.
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:

• Production of proerythroblasts from CFU-E of the bone marrow.
• Development of proerythroblasts into matured RBCs through the several stages
• Release of matured erythrocytes into blood.
• Some reticulocytes are also released along with matured RBCs.
2. Thyroxine
Being a general metabolic hormone, thyroxine accelerates the
process of erythropoiesis at many levels.

3. Hemopoietic Growth Factors or growth inducers: 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 (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.
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.
VARIATIONS IN NUMBER OF RED BLOOD
CELLS

PHYSIOLOGICAL VARIATIONS
A-Increase in RBC Count — Polycythemia:
The increase in number during this condition is marginal and temporary. It occurs in the
following conditions:
1. Age
2. Sex
3. High altitude
4. Muscular exercise
5. Emotional Conditions
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.
 B. Decrease in RBC Count
Decrease in RBC count occurs in the following physiological
conditions:

1. High Barometric Pressures

2. During Sleep
3. Pregnancy
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.
• Pathological 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 polycythemia 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.
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.
• Microcytes
Microcytes are present in:
i. Iron deficiency anemia
ii. Prolonged forced breathing
iii. Increased osmotic pressure in blood
Macrocytes
Macrocytes are present in:
i. Megaloblastic anemia
ii. Muscular exercise
iii. Decreased osmotic pressure in blood
Anisocytes
Anisocytes are found in pernicious anemia.
VARIATIONS IN SHAPE OF RED BLOOD CELLS

The shape of RBCs is altered in many conditions including different

types of anemia:
1. Crenation: Shrinkage as in hypertonic conditions
2. Spherocytosis: Globular form as in hypotonic conditions
3. Elliptocytosis: Elliptical shape as in certain types of anemia
4. Sickle cell: Crescentic shape as in sickle cell anemia.
5. Poikilocytosis: Unusual shapes due to deformed cell membrane. The
shape will be of flask, hammer or any other unusual shape.
 HEMOLYSIS AND FRAGILITY OF RBC

DEFINITION
Hemolysis
Hemolysis is the destruction of formed elements. To define more
specifically, it is the process, which involves the breakdown of RBC
and liberation of hemoglobin.
Fragility

The susceptibility of RBC to hemolysis or tendency to break easily is

called fragility (Fragile = easily broken).
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.
Hemoglobin
 Normal Hb types:

• Hb A:
• Hb A2:
• Hb F (Fetal Hb):
Variant forms of normal Hb:
• Oxyhemoglobin: hemoglobin combined with oxygen.
• Carboxyhemoglobin:hemoglobin combined with CO2
• Methemoglobin : Ferrous iron in converted into ferric iron.