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Circulatory System

Anatomy & Physiology

Beryl Ben C. Mergal, RN, MSN

The Circulatory System

Consists of the following:

Heart
Blood Vessels
Blood

Functions of the blood

1. Transport
Blood carries O2 from the lungs to all the of the bodys tissues, while
picking up CO2 from tissues and carries it to the lungs to be removed
from the body.
Picks up nutrients from the digestive tract and distributes them to all
tissues.
Carries metabolic wastes to the kidneys for removal.
Carries hormones from the endocrine cells to their target cells.

Functions of the blood

Functions of the blood

2. Protection
WBCs destroy microorganisms and cancer cells.
Antibodies and other blod proteins neutralize toxins and help to
destroy pathogens.
Plays an important role inflammation, a mechanism to limit the spread
of infection and promoting repair of injured tissue.
Platelets and other blood borne agenst initiate blood clotting and
other processes for minimizing blood loss.

Components and General

Properties of Blood
Blood - is a liquid connective tissue
composed of:

3. Regulation

Plasma a clear, light yellow fluid that forms

the extracellular matrix of the tissue.
Formed Elements are cells and cell
fragments (RBCs, WBCs and Platelets)

Blood maintains optima fluid balance and distributioin in the body by

absorbing or giving off fluid under different conditions.
Blood proteins stabilize the pH of extracellular fluids by buffering acids
and bases.
Shifts in blood flow help to regulate body temperature by routing
blood to the skin for heat loss or routing blood deeper to retain heat
in the body.

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Components of Blood

Plasma Composition
A mixture of water, proteins, nutrients,
nitrogenous wastes, hormones and gases.
A dilute solution which by weight is
approximately 92% H2O, 7% protein, and 1%
small dissolved dilutes.
Serum is the fluid that remains when blood
clots and the solids are removed.
Albumin is the smallest and most abundant
plasma protein. It transports various solutes and
buffers the pH of the plasma.

Albumin and Its Relationship to

the Physical Properties of Blood
Albumin influences greatly on the following
properties of blood:
1. Viscosity thickness or stickiness of a
fluid that results from cohesion of its
particles.
2. Osmolarity concentration of particles
that cannot pass through the walls of
blood vessels.

Major Types of Plasma Proteins

PLASMA
PROTEIN

MAJOR
SOURCE

EXAMPLES and FUNCTIONS

Albumin

Liver

Main component of plasma oncotic

pressure; binding of various
substances

-Globulins & Globulins

Liver

Examples include hormone-binding

proteins and the iron carrier protein
transferrin

Coagulation
proteins

Liver

Examples include plasminogen,

prothrombin, antithrombin III, and
fibrinogen

Immunoglobulins
Complement
Proteins

Lymphoid
Tissue

Host defense reactions

Liver

Host defense reactions

Normal Plasma Composition

SUBSTANCE

NORMAL VALUE

NORMAL RANGE

Sodium

140 mM

136-146 mM

Potassium

4.5 mM

3.5-5.5 mM

Chloride

100 mM

96-107 mM

Bicarbonate

24 mM

22-28 mM

Calcium

2.5 mM

2.2-2.8 mM

pH (arterial)

7.40

7.35-7.45

PCO2 (arterial)

40 mmHg

38-42 mmHg

PO2 (arterial)

90 mmHg

80-100 mmHg

Glucose (fasting)

80 mg/dL

70-99 mg/dL

Urea (BUN)

12 mg/dL

9-18 mg/dL

Protein

7 g/dL

6-8 g d/L

Formed (Cellular) Elements of

Blood
1. Red Blood Cells (erythrocytes)
essential for the transport of O2 and CO2
in blood. (approximately 5x10 12 RBC/L of
blood)
2. Platelets (thrombocytes) cellular
fragments that play a key role in
hemostasis by adhering to sites of
damage and through participation in the
blood clotting system. (approximately
300x109 platelets/L of blood)

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Cellular Elements of Blood

3. White Blood Cells (leukocytes) - fully
functional nuceated cells in the blood.
WBCs play a defensive role in destroying
infecting organisms and in the removal of
damaged tissue. (approximately 5x109
cells/L of bloos)

Hematopoiesis
It is the formation of blood cellular
components which primarily occurs in the
bone marrow.
Blood cells are derived from stem cells in
the bone marrow and are produced after
several stages of cell division and
differentiation.

Four Groups of Blood Forming

Cells during Hematopoiesis

General Properties of Blood

CHARACTERISTIC
Mean fraction of body
weight
Volume in adult body
Mean Temperature
pH

TYPICAL VALUES
FOR ADULTS
8%
Female: 4-5L; Male: 5-6 L
38C (100.4F)
7.35-7.45

Four Groups of Blood Forming

Cells during Hematopoiesis
1. Pluripotent hematopoetic stem cells
capable of forming any type of blood
cell.
2. Multipotential progenitor cells can
form a specific but wide range of blood
cells. There are 2 types
a. Lymphoid Cells
b. GEMM (granulocyte erythroid monocyte
megakaryocyte)

Hematopoiesis

3. Committed Progenitor Cells are

capable of self-renewal but are able to
form only one or two cell type.
4. Maturing Cells do not divide again and
are undergoing structural differentiation to
form a specific type of blood cell.

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Erythropoiesis
Erythropoietin (EPO) is
the primary regulator of
erythropoiesis and is
released from the kidney
when O2 tension in the renal
parenchyma is reduced.
The maturation of RBCs in
the bone marrow requires
several factors;
Iron (for the synthesis of
hemoglobin)
Folic Acid
Vit B12

Thrombopoiesis
Thrombopoietin (TPO) is a
cytokine that regulates platelet
formation. TPO is secreted by the
liver and kidneys.
Platelets remove TPO from the
circulation and so high levels of
TPO result when there is low
platelet count
(thrombocytopenia).
Increased TPO concentrations
stimulate megakaryotes to produce
more platelets and thereby restore
a normal platelet count.

Types of WBCs

General Features of the Process of

Stem Cell Differentiation (RBCs)
Cells decrease in size.
Hemoglobin is produced, which fills the
cytoplasm and causes the characteristic red
coloration.
The number of organelles decreases until all
eventually disappear from RBCs.
The nucleus gradually condenses and
disappears.
Reticulocytes (final stage) characterized by
presence of organelle remnants.

Leukopoiesis
Colony-Stimulating Factors is a
cytokine responsible for the production of
WBCs.
From a lymphoid progenitor cells in bone
marrow it then develops into:
T lymphocytes (differentiates in the thymus
gland)
B lymphocytes (differentiates in the lymph
nodes)

Leukemia

A general term used to describe a malignancy

characterized by the bone marrow becoming
infiltrated with malignant blast cells or immature
WBCs.

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Leukemia

Leukemia

When blast cells are of myeloid lineage the

condition is called Acute Myeloid Leukemia
(AML).

When blast cells are of lymphoid lineage the

condition is called Acute Lymphoblastic
Leukemia (ALL).

Common Symptoms of
Leukemia

Groups of Leukocytes
1. Granulocytes contain specific
lysosomes.
2. Agranulocytes they lack specific
granules.

Granulocytes
1. Neutrophils
Most abundant WBCs
They are aggressive
antibacterial cells where
they are quickly attracted
to areas of infection or
inflammation.
Uses phagocytosis to
digest bacteria.
Elevated neutrophils may
indicate an infection.

Granulocytes
2. Eosinophils
Represent only 2-4% of WBC total.
Secretes chemicals that weaken or
destroy large parasites such as
hookworms or tapeworms, which
are too large to be destroyed by
WBC.
Increased during parasitic
infections, allergies, and diseases
of the spleen and CNS and
fluctuates between day and night
during the course of the menstrual
cycle.

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Granulocytes

Granulocytes

3. Basophils

3. Basophils
Increased in diabetes,
chickenpox and
various other
diseases.

Rarest of the WBCs comprising only

0.5-1% of WBCs.
Secretes histamine, a vasodilator
that widens blood vessels, speeds
the flow of blood to injured tissue,
and makes the blood vessels more
permeable.
Secretes heparin, an anticoagulant
that inhibits blood clotting and thus
promotes the mobility of other WBCs
in the area.

Agranulocytes
4. Lymphocytes
Second to neutrophils
in abundance at 25%33%.
Increases in diverse
infectious diseases
and immune
responses.

The Leukocyte Life

Cycle
(Leukopoiesis)

Agranulocytes
5. Monocytes
Largest WBCs (in size).
About 3-8% of WBC count.
Transforms into macrophages
which destroys dead or dying
host and foreign cells,
microorganisms and other
foreign material, consuming up
to 25% of their own volume per
hour.
Increases in inflammation and
viral infections.

More Leukocyte Disorders

1. Leukopenia
low WBC count may be due to poisoning from
lead, mercury, or arsenic or to radiation
exposure.
Caused by diseases such as AIDS, measles,
mumps, chickenpox, influenza, and polio.
Certain drugs can also deplete WBC such as
glucocorticoids, anticancer drugs and
immunosuppressant drugs.

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More Leukocyte Disorders

2. Leukocytosis
Excessive number of WBCs.
May be due to infection or allergy, or even
dehydration or emotional disturbances.

Red Blood Cells

Key Cytoplasmic Proteins
1. Hemoglobin major protein present in red
blood cells, and is responsible for the
large O2-carrying capacity of blood.
2. Glycolytic Enzymes needed because
RBCs have no mitochondria and must
synthesize ATP via glycolysis
3. Carbonic Anhydrase for CO2 carriage in
blood

Red Blood Cells

Two Main Functions
1. To pick up oxygen
from the lungs and
transport it to body
tissues.
2. To pick up carbon
dioxide from the
tissues and unload it
in the lungs.

Red Blood Cells

Normal lifespan in the
circulation is
approximately 100-120
days.
Aging RBCs become
progressively more fragile
and are ultimately
removed from the
circulation by scavenging
macrophages (spleen).

Erythrocyte Life Cycle

Role of
Erythropoietin in
Regulation of
Erythropoiesis

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Red Blood Cells

Summary of Hb Breakdown

The end product of

hemoglobin breakdown in
macrophages is bilirubin,
which is conjugated in
the liver and excreted in
the bile.

Summary of Hb Breakdown

Red Blood Indices

INDEX

UNITS /
CALCULATION

Hemoglobin
Concentration (Hb)

g/dL

Adult man: 14-18 g/dL

Adult woman: 11-15 g/dL

Hematocrit (Hct)

Adult man: 40-54%

Adult woman: 34-46%

Red Blood Cell (RBC)

1012/L

Adult man: 4.5-6.5

Adult woman: 3.9-5.6

Mean Cell Volume

(MCV)

(% Hct 100) /
RBC (fL)

82-98 fL

Mean Cell Hemoglobin (Hb x 10)/ RBC

(MCH)
(pg)

27-33 pg

Mean Cell Hemoglobin (100 x MCH) /

Concentration (MCHC) MCV (g/dL)

30-35 g/dL

Red Blood Cell Indices

Red Blood Cell Indices

The size of the total RBC mass.

The size of an RBC

1. Hemoglobin concentration (Hb) is the

amount of hemoglobin in a volume of blood.
2. Hematocrit (Hct) or packed cell volume
(PCV) is the ratio of the volume of RBCs to
the volume of whole blood.
3. Red blood cell count (RBC) is the number
of RBCs per L of blood.

NORMAL RANGE

Mean Cell Volume (MCV) is a measure of

the average volume of a red blood cell
expressed in femtoliters (fL = 10-15 L).
MCV < 80 fL indicates that RBCs are small
(microcytosis)
MCV > 100 fL indicates that RBCs are large
(macrocytosis)

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Red Blood Cell Indices

Example:

The adequacy of hemoglobin synthesis:

A 42 y/o woman visits her family

doctor complaining of recent heavy
menses and a constant feeling of
fatigue. A CBC reveals Hb of 8 g/dL,
Hct of 24%, and RBC of 2.6 x 1012/L.
Calculate the MCV, MCH and MCHC.

1. Mean Cell Hemoglobin (MCH) is the

average amount of hemoglobin in the
average RBC, expressed in picograms (pg =
10-12 g)
2. Mean Cell Hemoglobin Concentration
(MCHC) is the average concentration of
hemoglobin in red cells.

Mean Cell Volume (MCV)

Mean Cell Hemoglobin (MCH)

MCV = (% Hct 100 ) (L)

= 24 100 / 2.6 x 1012 L
= 92 x 10-15 L = 92 fL

MCH = (Hb x 10)/RBC g

= 8 x 10/2.6 x 1012 g
= 30.8 x 10-12 g
= 30.8 pg

Normal range: 82 - 98
Normal range: 27-33

Mean Cell Hemoglobin

Concentration (MCHC)
MCHC = (100 x MCH)/MCV g/dL
=(100 x 30.8)/92 g/dL
=33.5 g/dL
Normal range: 30-35

Complementary RBC Indices

1. Blood smear to investigate variations
in cell size and cell shape which indicate
errors in RBC maturation.
2. Reticulocyte Count to assess rate of
RBC production.

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Anemia

General Causes of Anemia

Is a condition wherein there is reduction of

RBCs in the circulating blood. Often
recognized when laboratory tests are
abnormal.

ANEMIA
Hb, Hct

Count

High Reticulocyte
Count

Decreased RBC
Production

Accelerated RBC
Loss

Low Reticulocyte

Normal Cell Morphology

Examples:
Marrow Damage
Renal Failure ( EPO)

Laboratory Results for Types

of Anemia
FOLATE
CONTENT

RBC SIZE
(VOLUME)

Vit B12
Content

Normal

Low to
Normal

Low to
Normal

High

Normal to
slightly
High

Normal

Perniciou
s Anemia

Normal

Low

Low

High

High

Low

Hb

Hct

Fe
Content

Hemorrhagic Anemia
Acute
Blood Loss

Normal

Low to
Normal

Low to
Normal

Normal

Slightly
Low

Normal

Chronic
Blood Loss

Normal

Low

Low

Low

Low to
Normal

Normal

IDA

Normal

Low

Low

Low

Low

Normal

Hemolyti Normal
c Anemia

Low

Low

Normal to Normal to
High
High

Types of Anemia
Aplastic Anemia
Characterized by
abnormally low RBC
counts and
destruction of bone
marrow.

Examples:
Hemorrhage
Hemolysis

Types of Anemia

Aplastic
Anemia

ANEMIA

Abnormal Cell Morphology

Examples:
Folate deficiency/Vit.
B12 deficiency

Hemorrhagic Anemia
Caused by an actual
decrease in the
number of circulating
RBCs lost because of
hemorrhage or
bleeding.

Normal

Types of Anemia
Deficiency Anemia
1. Pernicious Anemia results from a
dietary deficiency of Vit B12.
2. Folate Deficiency Anemia results from
a dietary deficiency in Folic Acid.
3. Iron Deficiency Anemia results from a
deficiency in Iron.

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Types of Anemia
Hemolytic Anemias
1. Hemolytic Anemia is condition
characterized by a decrease in RBC life
span caused by an increased rate of
destruction of RBCs.
2. Sickle Cell Anemia is genetic disease
that results in the formation of limited
amounts of abnormal type of Hemoglobin

Types of Anemia

Sickle Cell Anemia

NORMAL

ABNORMAL

Common Symptoms of Anemia

Hemolytic Anemias
3. Thalassemia is a blood disorder passed
down through families (inherited) in which
the body makes an abnormal form
of hemoglobin, the protein in red blood
cells that carries oxygen. The disorder
results in excessive destruction of red
blood cells, which leads to anemia.

General Causes of Decreased

RBC Survival

Requirements for normal red

cell production

1. Hemorrhage causes immediate loss of

RBC.
2. Hemolytic Anemia is a form
of anemia due to hemolysis, the abnormal
breakdown of. red blood cells (RBCs)

1. Functional bone marrow

hypoproliferation of RBCs may result if the
bone marrow is damaged.
2. Erythropoietin secretion of EPO is
needed to stimulate the bone marrow.
3. Adequate nutrient supply for hemoglobin
synthesis such as iron deficiency.

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Polycythemia

Blood Types

It is an abnormally high level of circulating

red blood cells.
Caused primarily by increased levels of
EPO.
RBC mass causes viscosity of blood
and therefore risk for thrombosis

Blood types are based on interactions

between large molecules called antigens
and antibodies.
Antigens occur on the surface of cells and
enable the body distinguish its own cells
from foreign maater.
Antibodies are proteins produced by
certain white blood cells.

Blood Types

Blood Types

Agglutination is method of an antibody

action in which antibody molecules bind to
antigen molecules and stick them together.

ABO System of Typing:

1. Type A
2. Type B
3. Type AB
4. Type O

Blood Types

Blood Types

ABO System of Typing:

Rh System
Discovered in rhesus monkey in the year
1940.
Rh+ means individual have Rh antigen on
their RBCs.
Rh- means individual lacks Rh antigen on
their RBCs.

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Blood Types

erythroblastosis fetalis

Hemolytic disease of the newborn

(erythroblastosis fetalis)
The hemolytic condition occurs when there is an
incompatibility between the blood types of the
mother and the fetus.
Rhogam is the drug of choice. Stops the
mothers body from forming anti-Rh antibodies
and thus prevents the possibility of harm to the
next Rh+ baby.
In severe cases an exchange transfusion may be
indicated to replace the infants blood Rh Type.

Rh-positive blood cells enter the mother's

bloodstream during delivery of an Rh-positive
baby. If not treated, the mother's body will
produce anti-Rh antibodies.

erythroblastosis fetalis

erythroblastosis fetalis

A later pregnancy involving an Rh-negative

baby is normal because there are no Rh
antigens in the baby's blood.

A later pregnancy involving an Rh-positive

baby may result in erythroblastosis fetalis.
Anti-Rh antibodies enter the baby's blood
supply and cause agglutination of RBCs with
the Rh antigen.

Platelets
Platelets are small
circulating fragments
of bone marrow cells
called megakaryotes
and serve various
roles in blood clotting.
2nd most abundant
formed element.
Smaller than RBCs.

Platelets
Functions of Platelets
1. They secrete vasoconstrictors, chemicals that cause
spasmodic constriction of broken vessels and thus help
reduce blood loss.
2. They stick together to form temporary platelet plugs to
seal small breaks in injured blood vessels.
3. They secrete clotting factors that promote blood clotting.
4. They initiate the formation of clot-dissolving enzyme that
dissolves blood clots that have outlasted their
usefulness.
5. They secrete growth factors that stimulate mitosis in
fibroblasts and smooth muscle and thus help maintain
and repair blood vessels.

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Platelet Production

Role of Platelets in Blood

Clotting

Physiologic Mechanisms of
Hemostasis

Physiologic Mechanisms of
Hemostasis
1. Vascular Spasm
The prompt constriction of a broken vessel.
This narrows the opening and reduces
blood loss.
It is triggered in part by serotonin, a
vasoconstrictor secreted by the platelets.

Physiologic Mechanisms of
Hemostasis
2. Platelet Plug
A sticky mass of
platelets that acts as a
stopper to close small
breaks in a vessel.
(Primary
Hemostasis)

Physiologic Mechanisms of
Hemostasis
BLOOD CLOT FORMATION

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Physiologic Mechanisms of
Hemostasis

Phases of Primary Hemostasis

1. Platelet Adhesion to the exposed
subendothelial extracellular matrix which occurs
at the site of injury.
Adhesion is mediated by a variety of platelet receptors:
a) Integrin for binding to extracellular matrix proteins
(collagen)
b) Von Willebrand factor (vWF) promotes platelet
adhesions, forms crosslinks between platelets and
with collagen
c) Thromboxane A2 and thrombin further promotes
platelet adhesion and activation.

Von Willebrands Disease

(vWD)
Is the most common inherited bleeding
disorder and is characterized by either a
deficiency or a functional defect in vWF.

Phases of Primary Hemostasis

2. Platelet Activation
Several intracellular signaling pathways are
activated when ligands bind to platelet receptors.
Activated platelets then release many factors that
promote hemostasis:
a) ADP a potent activator for other platelets
b) Serotonin and Thromboxane A2 assists hemostasis as
vasoconstrictors.
c) vWF augments platelet adhesion and aggregation
d) Ca2+ and the clotting factors fibrinogen and factor V facilitate
coagulation.
e) Platelet-derived growth factor promotes wound healing and by
stimulating growth and migration of fibroblasts and smooth muscle cells
at the site of the injury.

Phases of Primary Hemostasis

3. Platelet aggregation completes the formation
of a platelet plug.
The signaling molecules released during platelet
activation amplify the platelet adhesion and
activation responses and recruit more platelets to
the site of injury.
Prostacyclin and nitric oxide prevents the
extension of a platelet plug from the injury site.

Physiologic Mechanisms of
Hemostasis
3. Coagulation (Clotting)
Occurs in which a fibrin mesh forms
together with platelets and other trapped
blood cells. (Secondary Hemostasis)

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Blood Coagulation Factors

FACTOR

NAME

FUNCTION OR PATHWAY

Fibrinogen

Converted to fibrin strands

II

Prothrombin

Converted to thrombin

III

Thromboplastin

Catalyzes conversion of
thrombin

IV

Calcium ions

Needed for all steps of

coagulation

Proaccelerin

Extrinsic/intrinsic pathways

VII

Serum prothrombin conversion

accelerator

Extrinsic Pathway

VIII

Antihemophilic factor

Intrinsic Pathway

IX

Plasma prothrombin component

Intrinsic Pathway

Stuart Factor

Extrinsic/Intrinsic Pathway

XI

Plasma Prothrombin antecedent

Intrinsic Pathway

XII

Hageman factor

Intinsic Pathway

XIII

Fibrin stabilizing factor

Cross-links fibrin strands to form

insoluble clot

Fibrinolysis
It is a normal body
process that keeps
naturally occurring blood
clots from growing and
causing problems.

Coagulation Cascade
INTRINSIC PATHWAY

EXTRINSIC PATHWAY
Damaged endothelial cells

Damaged endothelial cells

Activated factor XII

Factor III (Tissue Factor)

active XIa

Inactive XI
Inactive VIII

active VIIa

Inactive VII

active VIIIa
Inactive IX

Inactive IX

active IXa

Inactive X

Inactive X

active Xa

Prothrombin

Thrombin

Fibronogen

FIBRIN

Fibrinolysis

Tissue plasminogen activator

Urokinase-type plasminogen
activator

PLASMIN
2-antiplasmin

PLASMINOGEN

PLASMIN

Bleeding Disorders

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