Blood

Physiology
Content
• Polycythemia
• Blood cell indices and Packed cell volume
• White Blood Cells
• Genesis of White Blood Cells
• Types of White Blood Cells and their function
• Platelets
• Blood Coagulation
Polycythemia
• Higher number of RBCs in the blood
Packed Cell
Volume
• Hematocrit (HCT)
• HCT measures the volume of
packed red blood cells (RBC)
relative to whole blood.
• Simple test to identify conditions
like anemia/polycythemia
• Can monitor response to the
treatment.
• Normal adult male shows an HCT
of 40% to 54% and a female
shows 36% to 48%
• Wintrobe hematocrit tube
 Red Cell Indices

• Red blood cell indices ( RBC) are useful parameters when investigating
suspected anemia.
• RBC indices are calculated parameters that are part of an automated blood
count report.
• RBC indices have two primary uses:

1.Assist with the differentiation of anemias

2.Serve as quality control checks
• RBC indices include:
Mean Cell Volume (MCV)
Mean Cell Hemoglobin (MCH)
Mean Cell Hemoglobin Concentration (MCHC)

• First introduced by Wintrobe in 1929 to define the size (MCV) and

hemoglobin content (MCH, MCHC) of red blood cells.
• Red cell indices can be calculated if the values of hemoglobin, hematocrit
(packed cell volume), and red blood cell count are known
Mean Cell Volume (MCV)
• MCV defines the size of the red blood cells and is expressed as
femtoliters (10−15; fl)
• Average volume of the red blood cell (RBC)
• One femtoliter is 10-15 L.
• Reference interval for adults is typically 80 - 100 fL.
High MCV

When the MCV is higher than normal, red blood cells are larger than
normal.
This is called macrocytic anemia.

Macrocytic anemia can be caused by:

• Vitamin B-12 deficiency
• folate deficiency
• chemotherapy
• preleukemia
Low MCV

• When the MCV will be lower than normal, then the red blood cells are
too small. This condition is called microcytic anemia.

• Microcytic anemia may be caused by:

-Iron deficiency
-Thalassemia
-lead poisoning
-chronic diseases
Mean Cell Hemoglobin (MCH)
• The average weight of hemoglobin in the RBCs in the sample.
• Reporting units is picograms (pg)
• Reference interval for adults is typically 26 - 32 pg
Mean Cell Hemoglobin Concentration
(MCHC)
• Average concentration of hemoglobin in the RBCs contained within
the sample
• Reporting units is g/dL. Reference interval for adults is typically 32 -
36 g/dL.
• High MCH
• High MCHC means that the relative hemoglobin concentration per red blood
cell is high.

• MCHC can be elevated in diseases such as:

-Hereditary spherocytosis
-Sickle cell disease
-Homozygous hemoglobin C disease

• When the MCHC is high, the red cells are referred to as being hyperchromic.
Low MCHC
• Low MCHC means that the relative hemoglobin concentration per red blood
cell is low.
• The red blood cells will take on a lighter color when viewed under the
microscope.
• Individuals with anemia and a corresponding low MCHC are said to be
hypochromic.
• Conditions that can cause low MCHC include the same conditions that cause
low MCV including:
-Iron deficiency
- chronic diseases
- thalassemia
- lead poisoning
Iron deficiency anemia is described as microcytic and
hypochromic, whereas vitamin B12 deficiency is
macrocytic and normochromic.
https://www.youtube.com/watch?
v=d0GxAtkBrgQ&t=6s
Types of white blood cells

• Monocytes- garbage trucks of the immune system. clean up dead cells

• Lymphocytes- T cells being responsible for directly killing many foreign
invaders. B lymphocytes (B cells), in contrast to the other types of white blood
cells, are responsible for humoral immunity .
• produce the antibodies that "remember" an infection and stand ready in case
your body should be exposed
• Neutrophils- first cells of the immune system to respond to an invader such as a
bacteria or a virus.
• Basophils-
• Eosinophils- fighting off bacteria and are very important in
https://www.youtube.com/watch?v=V61n8a6dpO
responding to infections with parasites (such as worms)
White Blood Cells
( WBC) / Leukocytes
• White blood cells are
made in partially bone
marrow and partially
lymph tissues.

• Mobile units of body's

protective system

• Provide rapid and

potent defense
against infectious agents
Types of leukocytes
• Neutrophils
All cells have granular appearance
• Eosinophils Polymorphonuclear cells

• Basophils
• Monocytes
• Lymphocytes
 Type of WBC Concentration
Neutrophils 62%
Concentrations Eosinophils 2.3%
of different
white blood Basophils 0.4%
cells
Monocytes 5.3%
Lymphocytes 30%
 Genesis of the white blood cells
• Pluripotential hematopoietic stem cells

• Differentiated into myelocytes and lymphocytes

Granulocytes and monocytes are formed in the bone marrow

Lymphocytes and plasma cells are formed in the lymphogenous tissues like
lymph glands, spleen, thymus, tonsils and pockets of lymphoid tissue

White blood cells formed in the bone marrow are stored within the marrow
until needed
About three times as many white blood cells are stored in the marrow
Lymphocytes are stored in lymphoid tissues
Genesis of white blood
cells
Neutrophils
• First cells of the immune system to respond to an invader such as a
bacteria or a virus.
Monocytes
•Monocytes once enter the tissue, become larger and form tissue
macrophages
•Mainly neutrophils and tissue macrophages attack and destroy
invading bacteria, viruses and other injurious agents
•The important function of the neutrophils and macrophages is
phagocytosis.
•Phagocytosis is the cellular ingestion of the offending agent.
Factors depend on Phagocytosis

-Having smooth surfaces in the tissue

-Natural cells in the body have protective protein coats that repel the
phagocytes
- Immune system of the body
( develop antibodies against infectious agents, then adhere to the
agent membrane and make the agent susceptible to phagocytosis )
Eosinophils
•They are weak phagocytes
•Mostly produced for parasitic infections

lymphocytes
•Produce acquired immunity
 Basophils
• Basophils liberate heparin into the blood and prevent blood coagulation.
• Histamine, bradykinin and serotonin are also released.
• Act on allergic reactions.
- Antibody that cause for allergic reactions are called immunoglobulin E ( IgE)
They tend to attach with basophils.
When antigen specific for IgE reacts with the antibody , it leads to rupture the
basophil cell. This event release large amount of histamine, serotonin, heparin
and cause local vascular and tissue reactions
Platelets/ Thrombocytes
• Membrane-bound cell fragments that are essential for clot formation
during wound healing.
• Lack a nucleus, but do contain some organelles, such as mitochondria
and endoplasmic reticulum fragments.
• Irregularly shaped
• Cell fragments produced by megakaryocytes.
• Contain adhesive proteins that allow them to adhere to fibrin mesh
Platelet Formation
• Platelets are produced in the bone marrow,
• Platelets are produced from very large bone marrow cells called
megakaryocytes.
• As megakaryocytes develop into giant cells, they undergo a process of
fragmentation that results in the release of over 1,000 platelets per
megakaryocyte.
• The dominant hormone controlling megakaryocyte development is
thrombopoietin
Functions of the platelets
• Hemostasis is the natural process that stops blood loss when an injury
occurs.

• Platelets primarily involved in hemostasis (stopping the flow of blood

during injury), by causing the formation of blood clots, also known as
coagulation

• Adhesive surface proteins of platelets allow them to accumulate on the

fibrin mesh at an injury site to form a platelet plug that clots the blood.
• The complex process of wound repair can only begin once the clot has
stopped bleeding.
Blood Coagulation
Blood clotting mechanism is broken into 2 stages:
• Primary hemostasis: Formation of a weak platelet plug
• Secondary hemostasis: Stabilizing the weak platelet plug into a clot by
the fibrin network
Primary Hemostasis
• Primary hemostasis is the formation of a weak platelet plug.
• Four phases in forming a weak platelet plug
- vasoconstriction
- platelet adhesion
- platelet activation
-platelet aggregation

• Main purpose is stop bleeding

• Vascular Hemostasis-
• Vasoconstriction is a reflex in which blood vessels narrow to increase blood
pressure.
• It is a brief reflexive contraction that causes a decrease in blood flow to the
area.
• When an endothelial injury occurs, the endothelial cells stop secretion of
coagulation and aggregation inhibitors and instead secrete von Willebrand
factor, which causes platelet adherence during the initial formation of a clot.
Platelet Plug
• Within twenty seconds of an injury in which the blood vessel’s epithelial wall is disrupted,
coagulation is initiated

• platelet plug is completely formed by fibrin

• When the lining of a blood vessel breaks and endothelial cells are damaged, thromboxane
protein causes platelets to swell, grow filaments, and start clumping together, or
aggregating.

• Von Willebrand factor causes them to adhere to each other and the walls of the vessel.
This continues as more platelets gather and undergo these same transformations.

• This process results in a platelet plug that seals the injured area. If the injury is small, the
platelet plug may be able to form within several seconds.
Coagulation Cascade
• Platelets contain secretory granules

• When they stick to the proteins in the vessel walls, they degranulate, thus releasing their products,
which include ADP (adenosine diphosphate), serotonin, and thromboxane A2 (which activates
other platelets).
• Blood changes from a liquid to a gel

• At least 12 substances called clotting factors/ tissue factors take part in a cascade of chemical
reactions that eventually create a mesh of fibrin within the blood.

• Prothrombin, thrombin, and fibrinogen are the main factors involved in the outcome of the
coagulation cascade.

• Prothrombin and fibrinogen are proteins that are produced and deposited in the blood by the liver.
• When blood vessels are damaged,
vessels and nearby platelets are stimulated to release prothrombin
activator
This activates the conversion of prothrombin, a plasma protein, into an
enzyme called thrombin.
This reaction requires calcium ions.
Thrombin facilitates the conversion of a soluble plasma protein called
fibrinogen into long, insoluble fibers or threads of the protein, fibrin.
• Fibrin threads wind around the platelet plug at the damaged area of the blood vessel
• They form an interlocking network of fibers and a framework for the clot.
• This net of fibers traps and helps hold platelets, blood cells, and other molecules tight to
the site of injury, functioning as the initial clot.
• This temporary fibrin clot can form in less than a minute and slows blood flow before
platelets attach.
• Next, platelets in the clot begin to shrink, tightening the clot and drawing together the
vessel walls to initiate the process of wound healing.
• Usually, the whole process of clot formation and tightening takes less than a half hour.
• Vitamin K is an essential factor of the coagulation cascade.
• Coagulation involves a complex cascade in which a fibrin mesh is cleaved
from fibrinogen.
• Fibrin acts as a “molecular glue” during clot formation, holding the
platelet plug together

• Fibrin plays an essential role in hemostasis as both the primary product

of the coagulation cascade and the ultimate substrate for fibrinolysis.
 Fibrinolysis
• Fibrinolysis is a process that removes clots following hemostasis and clot
retraction, preventing uncontrolled thrombosis and embolism.

• There are two types of fibrinolysis:

• primary fibrinolysis and secondary fibrinolysis.
• Primary fibrinolysis is a normal body process
• secondary fibrinolysis is the breakdown of clots due to a medication,
medical disorder, or other cause.
 Primary Fibrinolysis
• Primary fibrinolysis normally occurs following clot retraction
• Main enzyme in primary fibrinolysis is plasmin
• It degrades fibrin mesh.
• Plasmin cleaves fibrin at various places, leading to the production of circulating
fragments that are cleared by other proteases or by the kidneys and liver.
• Plasmin is produced in an inactive form, plasminogen, in the liver.
• Plasminogen cannot cleave fibrin and circulates in the bloodstream.
• Instead, it is incorporated into the clot when it is formed and then activated
into plasmin later.
 Secondary Fibrinolysis
• Refers to treatment of pathological thromboembolism.
• if blood clots embolize to different parts of the body and cause tissue death by blocking
off blood flow to those tissues.
• This is a common cause of heart attacks, pulmonary embolism, and strokes. Several
medications exist to help treat and prevent these conditions.
• Fibrinolytic drugs include synthesized tissue plasminogen activator and streptokinase, a
bacterial enzyme that has degrades fibrin directly.
• Clots may also be prevented or kept from worsening through the use of blood thinners (
anticoagulants ).
• Aspirin has anticoagulant properties because it inhibits cyoclo-oxygenase dependent
pathways of platelet activation, which can prevent clotting from worsening.
• Heparin is a fast-acting anticoagulant produced by the body and used as a drug which
inhibits the activity of thrombin.
• Warfarin inhibits vitamin K cofactor activation during the coagulation cascade, and
citrates chelate calcium to prevent prothrombin activation into thrombin.