Introduction to the Cardiovascular System

A circulating transport system

A pump (the heart)

A conducting system (blood vessels)
A fluid medium (blood)

Is specialized fluid of connective tissue

Contains cells suspended in a fluid matrix

To transport materials to and from cells

Oxygen and carbon dioxide

Nutrients
Hormones
Immune system components
Waste products

Functions of Blood

Transport of dissolved substances

Regulation of pH and ions
Restriction of fluid losses at injury sites
Defense against toxins and pathogens
Stabilization of body temperature

Physical Characteristics of Blood

Whole Blood

Plasma

Fluid consisting of:

water
dissolved plasma proteins
other solutes

Formed elements

All cells and solids

Three Types of Formed Elements

Red blood cells (RBCs) or erythrocytes

Transport oxygen

White blood cells (WBCs) or leukocytes

Part of the immune system

Platelets

Cell fragments involved in clotting

Hemopoiesis

Process of producing formed elements

By myeloid and lymphoid stem cells

Fractionation

Process of separating whole blood for clinical analysis

Into plasma and formed elements

Three General Characteristics of Blood

38C (100.4F) is normal temperature

High viscosity
Slightly alkaline pH (7.357.45)

Blood volume (liters) = 7% of body weight (kilograms)

Adult male: 5 to 6 liters

Adult female: 4 to 5 liters

Plasma

Makes up 5060% of blood volume

More than 90% of plasma is water
Extracellular fluids

Interstitial fluid (IF) and plasma

Materials plasma and IF exchange across capillary walls

Water
Ions
Small solutes

Differences between Plasma and IF

Levels of O2 and CO2

Concentrations and types of dissolved proteins

Plasma proteins do not pass through capillary walls

Plasma Proteins

Albumins (60%)

Transport substances such as fatty acids, thyroid hormones, and steroid hormones

Globulins (35%)

Antibodies, also called immunoglobulins

Transport globulins (small molecules): hormone-binding proteins, metalloproteins,

apolipoproteins (lipoproteins), and steroid-binding proteins

Fibrinogen (4%)

Molecules that form clots and produce long, insoluble strands of fibrin

Serum

Liquid part of a blood sample

In which dissolved fibrinogen has converted to solid fibrin

Other Plasma Proteins

1% of plasma

Changing quantities of specialized plasma proteins

Enzymes, hormones, and prohormones

Origins of Plasma Proteins

90% + made in liver

Antibodies made by plasma cells
Peptide hormones made by endocrine organs

Red Blood Cells

Red blood cells (RBCs) make up 99.9% of bloods formed
elements
Hemoglobin

The red pigment that gives whole blood its color

Binds and transports oxygen and carbon dioxide

Abundance of RBCs

Red blood cell count: the number of RBCs in 1 microliter of whole blood

Male: 4.56.3 million

Female: 4.25.5 million

Hematocrit (packed cell volume, PCV): percentage of RBCs in

centrifuged whole blood

Male: 4054
Female: 3747

Structure of RBCs

Small and highly specialized discs

Thin in middle and thicker at edge

Importance of RBC Shape and Size

High surface-to-volume ratio

Quickly absorbs and releases oxygen

Discs form stacks called rouleaux

Smooth the flow through narrow blood vessels

Discs bend and flex entering small capillaries:

7.8 m RBC passes through 4 m capillary

Lifespan of RBCs

Lack nuclei, mitochondria, and ribosomes

Means no repair and anaerobic metabolism

Live about 120 days

Hemoglobin (Hb)

Protein molecule, that transports respiratory gases

Normal hemoglobin (adult male)

1418 g/dL whole blood

Normal hemoglobin (adult female)

1216 g/dL, whole blood

Hemoglobin Structure

Complex quaternary structure

Four globular protein subunits:

Each with one molecule of heme

Each heme contains one iron ion

Iron ions

Associate easily with oxygen (oxyhemoglobin)

OR

Dissociate easily from oxygen (deoxyhemoglobin)

Fetal Hemoglobin

Strong form of hemoglobin found in embryos

Takes oxygen from mothers hemoglobin

Hemoglobin Function

Carries oxygen
With low oxygen (peripheral capillaries)

Hemoglobin releases oxygen

Binds carbon dioxide and carries it to lungs

Forms carbaminohemoglobin

RBC Formation and Turnover

1% of circulating RBCs wear out per day

About 3 million RBCs per second

Macrophages of liver, spleen, and bone marrow

Monitor RBCs
Engulf RBCs before membranes rupture (hemolyze)

Hemoglobin Conversion and Recycling

Phagocytes break hemoglobin into components

Globular proteins to amino acids

Heme to biliverdin
Iron

Hemoglobinuria

Hemoglobin breakdown products in urine due to excess hemolysis in bloodstream

Hematuria

Whole red blood cells in urine due to kidney or tissue damage

Iron Recycling

Iron removed from heme leaving biliverdin

To transport proteins (transferrin)
To storage proteins (ferritin and hemosiderin)

Breakdown of Biliverdin

Biliverdin (green) is converted to bilirubin (yellow)

Bilirubin is:

excreted by liver (bile)

jaundice is caused by bilirubin buildup
converted by intestinal bacteria to urobilins and stercobilins

RBC Production

Erythropoiesis

Occurs only in myeloid tissue (red bone marrow) in adults

Stem cells mature to become RBCs

Hemocytoblasts

Stem cells in myeloid tissue divide to produce

Myeloid stem cells: become RBCs, some WBCs

Lymphoid stem cells: become lymphocytes

Stages of RBC Maturation

Myeloid stem cell

Proerythroblast
Erythroblasts
Reticulocyte
Mature RBC
Regulation of Erythropoiesis

Building red blood cells requires

Amino acids
Iron
Vitamins B12, B6, and folic acid:
pernicious anemia

low RBC production

due to unavailability of vitamin B12

Stimulating Hormones

Erythropoietin (EPO)

Also called erythropoiesis-stimulating hormone

Secreted when oxygen in peripheral tissues is low (hypoxia)
Due to disease or high altitude

Blood Typing

Are cell surface proteins that identify cells to immune system

Normal cells are ignored and foreign cells attacked
Blood types

Are genetically determined

By presence or absence of RBC surface antigens A, B, Rh (or D)

Four Basic Blood Types

A (surface antigen A)
B (surface antigen B)

AB (antigens A and B)
O (neither A nor B)

Agglutinogens

Antigens on surface of RBCs

Screened by immune system

Plasma antibodies attack and agglutinate (clump) foreign

antigens

Blood Plasma Antibodies

Type A

Type B antibodies

Type B

Type A antibodies

Type O

Both A and B antibodies

Type AB

Neither A nor B antibodies

The Rh Factor

Also called D antigen

Either Rh positive (Rh+) or Rh negative (Rh-)

Only sensitized Rh- blood has anti-Rh antibodies

Cross-Reactions in Transfusions

Also called transfusion reaction

Plasma antibody meets its specific surface antigen
Blood will agglutinate and hemolyze
Occur if donor and recipient blood types not compatible

Cross-Match Testing for Transfusion Compatibility

Performed on donor and recipient blood for compatibility

Without cross-match, type O- is universal donor

White Blood Cells

Also called leukocytes

Do not have hemoglobin
Have nuclei and other organelles
WBC functions

Defend against pathogens

Remove toxins and wastes

Attack abnormal cells

WBC Circulation and Movement

Most WBCs in

Connective tissue proper

Lymphoid system organs

Small numbers in blood

5000 to 10,000 per microliter

Characteristics of circulating WBCs

Can migrate out of bloodstream

Have amoeboid movement
Attracted to chemical stimuli (positive chemotaxis)
Some are phagocytic:

neutrophils, eosinophils, and monocytes

Types of WBCs

Neutrophils
Eosinophils
Basophils
Monocytes
Lymphocytes

Neutrophils

Also called polymorphonuclear leukocytes

5070% of circulating WBCs
Pale cytoplasm granules with

Lysosomal enzymes
Bactericides (hydrogen peroxide and superoxide)

Neutrophil Action

Very active, first to attack bacteria

Engulf pathogens
Digest pathogens

Degranulation:

removing granules from cytoplasm

defensins (peptides from lysosomes) attack pathogen membranes

Release prostaglandins and leukotrienes

Form pus

Eosinophils

Also called acidophils

24% of circulating WBCs
Attack large parasites
Excrete toxic compounds

Nitric oxide

Cytotoxic enzymes

Are sensitive to allergens

Control inflammation with enzymes that counteract inflammatory effects of

neutrophils and mast cells

Basophils

Are less than 1% of circulating WBCs

Are small
Accumulate in damaged tissue
Release histamine

Dilates blood vessels

Release heparin

Prevents blood clotting

Monocytes

28% of circulating WBCs

Are large and spherical

Enter peripheral tissues and become macrophages

Engulf large particles and pathogens

Secrete substances that attract immune system cells and fibrocytes to

injured area

Lymphocytes

2030% of circulating WBCs

Are larger than RBCs
Migrate in and out of blood
Mostly in connective tissues and lymphoid organs
Are part of the bodys specific defense system

Three Classes of Lymphocytes

T cells

Cell-mediated immunity
Attack foreign cells directly

B cells

Humoral immunity
Differentiate into plasma cells
Synthesize antibodies

Natural killer (NK) cells

Detect and destroy abnormal tissue cells (cancers)

The Differential Count and Changes in WBC Profiles

Detects changes in WBC populations

Infections, inflammation, and allergic reactions

WBC Disorders

Leukopenia

Abnormally low WBC count

Leukocytosis

Abnormally high WBC count

Leukemia

Extremely high WBC count

WBC Production

All blood cells originate from hemocytoblasts

Which produce myeloid stem cells and lymphoid stem cells

Myeloid Stem Cells

Differentiate into progenitor cells, which produce all WBCs except lymphocytes

Lymphoid Stem Cells

Lymphopoiesis: the production of lymphocytes

WBC Development

WBCs, except monocytes

Develop fully in bone marrow

Monocytes

Develop into macrophages in peripheral tissues

Regulation of WBC Production

Colony-stimulating factors = CSFs

Hormones that regulate blood cell populations:

1. M-CSF stimulates monocyte production

2. G-CSF stimulates granulocyte (neutrophils, eosinophils, and basophils) production
3. GM-CSF stimulates granulocyte and monocyte production
4. Multi-CSF accelerates production of granulocytes, monocytes, platelets, and RBCs

Platelets

Cell fragments involved in human clotting system

Nonmammalian vertebrates have thrombocytes (nucleated cells)

Circulate for 912 days

Are removed by spleen
2/3 are reserved for emergencies

Platelet Counts

150,000 to 500,000 per microliter

Thrombocytopenia

Abnormally low platelet count

Thrombocytosis

Abnormally high platelet count

Three Functions of Platelets:

1.
2.
3.

Release important clotting chemicals

Temporarily patch damaged vessel walls
Actively contract tissue after clot formation
Platelet Production

Also called thrombocytopoiesis

Occurs in bone marrow

Megakaryocytes

Giant cells in bone marrow

Manufacture platelets from cytoplasm

Platelet Production

Hormonal controls

Thrombopoietin (TPO)
Interleukin-6 (IL-6)
Multi-CSF

Hemostasis

Hemostasis is the cessation of bleeding

Consists of three phases

Vascular phase
Platelet phase
Coagulation phase
The Vascular Phase

A cut triggers vascular spasm that lasts 30 minutes

Three steps of the vascular phase

Endothelial cells contract:

expose basal lamina to bloodstream

Endothelial cells release:

chemical factors: ADP, tissue factor, and prostacyclin

local hormones: endothelins
stimulate smooth muscle contraction and cell division

Endothelial plasma membranes become sticky:

seal off blood flow

The Platelet Phase

Begins within 15 seconds after injury

Platelet adhesion (attachment)

To sticky endothelial surfaces

To basal laminae
To exposed collagen fibers

Platelet aggregation (stick together)

Forms platelet plug

Closes small breaks

Platelet Phase

Activated platelets release clotting compounds

Adenosine diphosphate (ADP)

Thromboxane A2 and serotonin
Clotting factors
Platelet-derived growth factor (PDGF)
Calcium ions

Factors that limit the growth of the platelet plug

Prostacyclin, released by endothelial cells, inhibits platelet aggregation

Inhibitory compounds released by other white blood cells
Circulating enzymes break down ADP
Negative (inhibitory) feedback: from serotonin
Development of blood clot isolates area

The Coagulation Phase

Begins 30 seconds or more after the injury

Blood clotting (coagulation)

Cascade reactions:

chain reactions of enzymes and proenzymes

form three pathways
convert circulating fibrinogen into insoluble fibrin

Clotting Factors

Also called procoagulants

Proteins or ions in plasma
Required for normal clotting
Three Coagulation Pathways

Extrinsic pathway

Begins in the vessel wall

Outside bloodstream

Intrinsic pathway

Begins with circulating proenzymes

Within bloodstream

Common pathway

Where intrinsic and extrinsic pathways converge

The Extrinsic Pathway

Damaged cells release tissue factor (TF)

TF + other compounds = enzyme complex
Activates Factor X

The Intrinsic Pathway

Activation of enzymes by collagen

Platelets release factors (e.g., PF3)

Series of reactions activates Factor X

The Common Pathway

Forms enzyme prothrombinase

Converts prothrombin to thrombin
Thrombin converts fibrinogen to fibrin

Stimulates formation of tissue factor

Stimulates release of PF-3

Forms positive feedback loop (intrinsic and extrinsic)

Accelerates clotting

Clotting: Area Restriction

Anticoagulants (plasma proteins)

Antithrombin-III
Alpha-2-macroglobulin

Heparin
Protein C (activated by thrombomodulin)
Prostacyclin

Calcium Ions, Vitamin K, and Blood Clotting

Calcium ions (Ca2+) and vitamin K are both essential to the

clotting process

Clot Retraction

After clot has formed

Platelets contract and pull torn area together

Takes 3060 minutes

Fibrinolysis

Slow process of dissolving clot

Thrombin and tissue plasminogen activator (t-PA):

activate plasminogen

Plasminogen produces plasmin

Digests fibrin strands