HPH S4004- HL01/02- 2016S2

Anatomy and Physiology II

Lecture 1
Blood
Jeff Tjong, PhD
jeff.tjong@hkuspace-plk.hku.hk

http://archive.cnx.org/contents/fd78a9c0-a232-4b11-b3a3-ab6955731177@4/components-of-the-blood

I. Components of the blood

A.
B.
C.
D.
E.
F.

Blood
Composition of blood
Blood plasma
Blood cells
Red blood cells
White blood cells

A. blood

A type of connective tissue whose cells are

suspended in a liquid extracellular matrix.

Make up 6-8% of total body weight.

Normal adult blood volume is around 5L.

~2L= blood cells
~3L= Plasma fluid portion of blood

pH is between 7.35 and 7.45.

1. Functions of blood
1. Distribution and transportation

2. Regulation

3. Protection

Oxygen and carbon dioxide by red blood cells.

Nutrients from gastrointestinal tract to body cells.

Nitrogenous wastes from body cells to kidneys.

Hormones from glands to body cells.

Maintenance of normal body pH.

Maintenance of circulatory/interstitial fluid.

Body temperature.

Blood clotting following a wound.

White blood cells against microbes.

B. Blood component

Composed of the formed elements (45%) and the plasma (55%).

C. Blood plasma

Pale yellow sticky liquid.

Major component of blood that consists of about 90% water which dissolves and
transports organic and inorganic molecules.
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1. Plasma proteins

Most abundant of the solutes in plasma.

Remain in the blood and interstitial fluids, and ordinarily are not used as energy
sources.

Fibrinogens (4%)

Three major types

1)

Albumins
Globulins (36%)

2)

Globulins

3)

fibrinogens

Albumins (60%)

Albumins

Synthesized in the liver.

Smallest of the plasma proteins.

Important determinant of the osmotic

pressure of the plasma that regulate
interstitial fluid volume directly.
Important in transport of fatty acids, thyroid
and some steroid hormones, and other
substances.
Fibrinogen

Synthesized in the liver.

Functions in blood clotting

a- globulin

Synthesized in the liver.

Transport lipids and fat soluble vitamins

(Vitamin A,D, E and K)

b-globulin

Synthesized in the liver.

Transport lipids and fat soluble vitamins

g-globulin

Secreted from lymphatic

tissues.

Constitute a type of antibody

Globulins

D. Blood cells (formed elements)

The actual cellular components of blood.

1. Erythrocytes: red blood cells (RBCs).
2. Leukocytes: white blood cells (WBCs).
3. Platelets: cell fragments for clotting.

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1. Hematopoiesis

All blood-borne cells ultimately derive from pluripotent hematopoietic stem cells, which has
the capacity to produce all leukocytes as well as red blood cells and platelets.
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Age

Site of Hematopoiesis

Embryo

yolk sac produces stem cells

colonize fetal bone morrow, liver, spleen and thymus.

Birth

Mostly bone marrow; spleen and liver when needed

Adult

bone marrow of skull, ribs, sternum, vertebral column, pelvis, proximal ends
of femurs

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D. Erythrocytes (Red blood cells)

Biconcave disk shape that is ideal for gas

exchange.

DO NOT have nucleus, mitochondria and

ribosomes.

Contain haemoglobin (33% of cell mass)

carrying oxygen.

Normal male count: 5.1-5.8 million /mm3

Normal female count: 4.2-5.2million /mm3

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1. Erythropoiesis

Red blood cell formation

Embryo and fetus: occurs in the yolk sac, liver an spleen

Adult: occurs in MYELOID TISSUE of red bone marrow

Iron is a key component of haemoglobin. Erythropoiesis

contain 80% of the odys iron.

Types of bone marrow

1.

Red marrow: active blood cell production occurs;

located in portions of vertebrate, ribs, pelvis, and
proximal limb bones.

2.

Yellow marrow: fatty tissue in other marrow.

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2. Erythrocytes life cycle

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RBCs are broken down and components are recycled:

1. Goblin portion is broken down into amino acids and used to create new proteins.
2. Heme portion split into iron (Fe3+) which is used for hemoglobin synthesis in bone marrow.
3. The heme is further decomposed into biliverdin which is converted into bilirubin ( yellow ).
The bilirubin is secreted in the liver and excreted in bile.

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3. Regulation of Erythropoiesis

An increase in erythropoietin happen during low oxygen level in the blood due to:
1. Reduced RBCs (anemia)
2. Reduced oxygen tension (at high altitude)
3. Increased demand of oxygen in tissue (during exercise)
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4. Dietary Factors Affecting Red Blood Cell Production

1.

Essential coenzymes
Vitamins B6, B12 and folic acid.
Necessary for DNA replication
(Mitosis).

2.

Iron
Needed for hemoglobin synthesis.

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F. White blood cells (Leukocytes)

Around 5,000-10,000 white blood cells/ml of blood.

Against infection by patrolling the tissues and organs the body via the blood
circulatory and lymphatic systems.
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1. Classifications of Leukocytes

Broadly classified by the absence

(agranular) or presence (granular) of
cytoplasmic inclusions or granules

Formed in two regions:

1. Bone
marrow:
granulocytes,
monocytes and a few lymphocytes.
2. Lymph tissue:
plasma cells.

lymphocytes

and

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1.1 Neutrophils

Also called polymorphonuclear (PMN) cells

because of variable number of nuclear segment
(2-5 lobes).

Comprise 60-70% of circulating leukocytes.

Destroy and ingest bacteria and fungi.

With a half-life of ~7 hrs, over 100 billion

neutrophils enter the circulation daily in normal
adults. Upon activation, they survive for 1-2days.

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1.2 Eosinophil

Make up 1-4% of circulating leukocytes.

Phagocytic and are particularly involved

in the destruction of parasitic worms but
may also contribute to allergic response.

Persist in the circulation for 8-12 hrs,

and can survive in tissue for an
additional 8-12 days in the absence of
stimulation.

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1.3 Basophils

Account for under 0.5% of leukocytes.

Phagocytic that release histamine and

heparin.

Involved in allergic responses.

Granules
contains
histamine,Heparan
sulfate and hydrolytic enzymes

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1.4 Monocytes

Constitute 2-5% of leukocytes

Have the greatest phagocytic potential of all body cells

They spend 1-2 days in circulation, then enter throughout the body, where they
reside for up to several months as macrophages.
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1.5 Macrophages

Scavengers of the body.

They phagocytize, or pick up cellular debris, foreign cells, and particles and
degrade them enzymatically.

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1.6 Dendritic cells

Named for their branchlike

cytoplasmic projections.
They actively engulf cells and
particles in their environment by
phagocytosis.
As actively phagocytic cells,
dendritic cells are important in
innate immune defenses.

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1.7 Natural killer (NK) cells

Account for 5%-10% of all lymphocytes in circulation.

Named for their ability to lyse and kill virus-infected cells and cancer cells.

Kill the cells by releasing perforins and other cytolytic substances.

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1.8 T- and B- cells

T-cell

T stands for thymus while B stand for bursa,

organs in which their final stage of development
occurs.

The function of T and B cells is to recognize specific

non-self antigens. Once they have identified an
invader, the cells generate specific responses that
eliminate specific pathogens or pathogen infected
cells.
B-cell

T-cells play critical roles in the adaptive immune

responses.

B cells produces large quantities of antibodies which

then neutralize foreign object like bacteria and virus.

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II. Blood groups and blood transfusion

A. Antigens and antibodies
B. Blood types
C. Blood transfusion

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A. Antigens and Antibodies

Antigen

Antibodies ( agglutinins)

Usually proteins that can trigger an contained in plasma that attack

immune response.
antigens on foreign RBCs.

Cell membrane antigens are termed as

agglutinogens that are glycoproteins or
glycolipids.

Characteristics are genetically determined.

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When agglutinins attack the foreign RBCs, foreign cells clump together or
agglutinate, the process is termed as agglutination.

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B. Blood types

Determined by presence or absence of specific surface antigen in RBC cell membrane A, B, Rh (D).
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1. Rhesus (Rh) Blood Types

Discovered in 1940 by Karl Landsteiner and Alexander Wiener where it was named after the
Rhesus monkey.

Rh (+) positive means the RBCs have antigens on their surface, whereas Rh (-) negative means
RBCs do not have D antigen on their surface.

The type D antigen is widely prevalent in the population. About 85 per cent of all white people
are Rh positive and 15 per cent, Rh negative.
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If an Rh(-) person receives a transfusion of Rh (+) blood, the Rh antigen stimulates the
recipient to begin producing anti-Rh antibodies.

Generally, this initial transfusion has no serious consequences.

However, if the Rh (-) person, who is not sensitized to Rh (+) blood, receives another
transfusion of Rh (+) blood some month later, the donated blood is likely to
agglutinate.
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C. Blood transfusion

Blood types of donor and recipient must be compatible.

Cross-match test: exposing donors RBCs to sample of re ipients plasma under

controlled conditions.
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III. Blood coagulation

A. Platelets
B. Hemostasis
C. Mechanisms of blood coagulation

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A. Platelets

fragments of megakaryocytes.

Responsible for clotting of blood.

Responsible for clotting of the blood for repair of damaged tissue.

Normal counts: 130,000- 360,000 platelets/mm3.

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1. Thrombocytopoiesis

Platelet production.

occurs in bone marrow.

Around 1/3 of platelets in body at any

moment are held in spleen and other
vascular organs rather than in circulation.

Each one circulates 9-12 days before

being removed by phagocytes, mainly in
spleen.

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2. Roles of platelets

1.

Formation of platelet plug in the walls of damaged blood vessels that can slow
rate of blood loss while clotting occurs.

2.

Help initiate and control clotting process

3.

Transport of chemical involved in clotting process.

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B. Hemostasis

Refers to the stoppage of bleeding to:

Minimizes blood loss through walls of damaged vessels
Maintenance of blood volume

Establishes framework for tissue repairs via three mechanisms:

1. Blood vessel spasm
2. Platelet plug formation
3. Blood coagulation (blood clotting)
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1. Blood vessel spasm

Cutting wall of blood vessel triggers

control in smooth muscle of vessel wall.

Reduce diameter of vessel at site of injury

that decrease the blood flow to the
damaged vessel.

Last for few minutes, but long enough to

initiate the following steps of hemostasis.

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2. Platelet plug formation

Platelets attach to the exposed edges of damaged blood vessels, causing a series of
reaction that results in massive platelet plug at the site of damage.

Most effective on a SMALL VESSEL.

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1.

Platelet adhesion

Platelets stick to exposed collagen underlying

damaged endothelial cells in vessel wall.

2.

Platelet release reaction

Platelets activated by adhesion, followed by

extending projections to make contact with
each other.

Release ADP, vasoconstrictors (thromboxane

A2) and serotonin to further decrease blood
flow.

3.

Platelet plug formation

Activated platelets stick together and activate

new platelets to form platelet plug.

Plug reinforced by fibrin threads formed

during coagulations process.

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3. Blood coagulation

The most effective mechanism of haemostasis.

Complicated process and involvement of clotting factors.

The major event in blood clot formation is the conversion of SOUBLE fibrinogen into
INSOLUBLE fibrin.
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1.

The clot begins to develop in 15-20 seconds if the

trauma to the vascular wall has been severe.

2.

Platelets agglutinate on the wall of blood vessel.

3.

Fibrinogen is converted into fibrin.

4.

Once a blood clot forms, it promotes still more

clotting through a positive feedback system.
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5. A clot that forms abnormally in a vessel is a

thrombus, if it dislodges, it is an embolus.
5

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C. Mechanisms of blood coagulation

Clotting factors
1. Released from platelets and injury tissue
2. Plasma proteins synthesized in liver and circulating
in inactive form

Prothrombin
circulating in plasma

Thrombin
[Ca2+]

Fibrinogen
Common pathway

Intrinsic/ extrinsic pathway

Fibrinogen
monomer

Activated fibrinStabilizing factor

[Ca2+]

Fibrin fibers

Cross-linked fibrin fibers

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Three essential steps:

1.

In response to the rupture of the blood vessel, several blood coagulation factors
involved in the formation of a complex of activated substances collectively called
Prothrombin activator.

2.

The prothrombin activator catalyses conversion of prothrombin into thrombin.

3.

The thrombin acts a an enzyme to convert fibrinogen into fibrin fibers that
enmesh platelets, blood cells and plasma to form a clot.

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Two clotting pathways occur simultaneously:

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1. Intrinsic pathway
Blood trauma or contact with collagen
1

XII
2

Activated XII (IIa)

XI

Activated XI (Ia)
[Ca2+]

IX

VIII

Activated IX (IXa)

VIIIa

4
[Ca2+]

Platelet
phospholipids

Activated X (Xa)

[Ca2+]

Prothrombin
V

5
Prothrombin activator

[Ca2+]

Thrombin

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1.

Blood trauma causes

a.
Activation of factor XII
b. Release of platelet phospholipids
c.
Factor XII is converted into a proteolytic enzyme termed as activated Factor XII
(IIa)

2.

The activated factor XII acts enzymaticaly on factor XI to activate this factor.

3.

The activated Factor XI then acts enzymatically on Factor IX to activate this factor.

4.

The activated Factor IX, acting in concert with acivated Factor VIII with the platelet
phospholipids and factor 3 from the traumatized platelets, activates Factor X.

5.

Activated Factor X to form prothrombin activator

Same as last step in the extrinsic pathway.
Activated Factor X combine with Factor V and platelet or tissue phospholipids
to form prothromin activator, in turn initiates the cleavage of prothrombin to
form thrombin.
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2. Extrinsic pathway
Tissue trauma

VII
Tissue factor
2

VIIa
Activated X (Xa)

[Ca2+]

[Ca2+]

V
Platelet
phospholipids

Prothrombin activator

Thrombin

Prothrombin
[Ca2+]

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1. Traumatized tissue release a complex of several factors termed as tissue factor (or
throboplastin). This factor is composed of phospholipids and lipoprotein (serve as
proteolytic enzyme).

2. The tissue factor with blood coagulation factor VII, and in the presence of Ca2+ ions,
act enzymatically on Factor X to form activated Factor X (Xa).
3. Effect of Factor Xa to form prothrombin activator
Factor X combines with tissue phospholipids or with additional phospholipids
released from platelets as well as Factor V to form prothrombin activator.
In the presence of Ca2+ ions, prothrombin is spited to form thrombin.

Noted that at first, factor V in the prothrombin activator complex is INACTIVE. But
once clotting begins and formation of thrombin, the proteolytic action of
thrombin activates factor V. This then becomes an additional strong accelerator
of prothrombin activation (positive feedback effect of thrombin).

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3. Intrinsic vs extrinsic pathways

Extrinsic pathway

Intrinsic pathway

Arises if only cells surrounding the Arises if the endothelium is damaged ( blood
blood vessel are damaged
contacting collagen + platelets being damaged
by cut edges of the vessel wall)

Initiation by tissue factor

Initiation by contact of Factor XII and platelets

with collagen in the vascular wall.

Explosive that the clotting can occur Much slower to proceed, usually requiring 1 to
in 15 seconds.
6 minutes to cause clotting.

http://www.hopkinsmedicine.org/hematology/coagulation.swf

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4. Inhibition of blood coagulation

Excessive blood clotting would be dangerous if blood clotting were to continue to

expand beyond the boundaries of the injury.

1.

Clotting factors are rapidly inactivated to ensure that clotting is only occur at the
site of injury and not progress steadily down the vessel.

2.

Fibrin fibers inhibit the activity of thrombin (negative feedback loop):

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5. Lysis of blood clot

Blood clots facilitate the tissue repair. When the

vessel is healed, the blood clot is no longer
needed.
1. The clot itself stimulates the secretion
of tissue plasminogen activator (TPA) from
the surrounding vascular epithelium.
2. TPA is an enzyme that catalyzes the
conversion of plasminogen to plasmin.
3. Plasmin digests fibrin fibers and some other
protein coagulants such as fibrinogen, Factor
V, Factor VIII, prothrombin, and Factor XII.

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6. Anticoagulants

Substances that inhibit the process of clotting

Heparin

Coumadin
(warfarin)

Citrates

Produced primarily in liver and lung.

Inhibits the activity of thrombin.

Used clinically for acute conditions, also used to prevent clotting in IV

Inhibiting the processing of vitamin K, which is required for the synthesis of

several clotting factors including Prothrombin.

Taken orally in small doses for chronic control of blood clotting.

Slow acting, requiring days to have an effect.

Bind up (chelate) calcium and thus inhibit the formation of clots.

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