Chapter 19: The Cardiovascular System: The Bloodcpha.tu.edu.iq/images/lec_5_blood.pdf · 1 Red blood cell Platelet Collagen fibers and damaged endothelium 1 Platelet adhesion 2 Liberated

Copyright 2009, John Wiley & Sons, Inc.

Chapter 19: The Cardiovascular

System: The Blood


Blood

Liquid connective tissue

3 general functions

1. Transportation

Gases, nutrients, hormones, waste products

2. Regulation

pH, body temperature, osmotic pressure

3. Protection

Clotting, white blood cells, proteins


Components of Blood

Blood plasma – water liquid extracellular matrix

91.5% water, 8.5% solutes (primarily proteins)

Hepatocytes synthesize most plasma proteins

Albumins, fibrinogen, antibodies

Other solutes include electrolytes, nutrients, enzymes,

hormones, gases and waste products

Formed elements – cells and cell fragments

Red blood cells (RBCs)

White blood cells (WBCs)

Platelets



Formed Elements of Blood


Formation of Blood Cells

Negative feedback systems regulate the total

number of RBCs and platelets in circulation

Abundance of WBC types based of response

to invading pathogens or foreign antigens

Hemopoiesis or hemotopoiesis

Red bone marrow primary site

Pluripotent stem cells have the ability to

develop into many different types of cells




Stem cells in bone marrow

Reproduce themselves

Proliferate and differentiate

Cells enter blood stream through sinusoids

Formed elements do not divide once they

leave red bone marrow

Exception is lymphocytes



Pluripotent stem cells produce

Myeloid stem cells

Give rise to red blood cells, platelets, monocytes, neutrophils,

eosinophils and basophils

Lymphoid stem cells give rise to

Lymphocytes

Hemopoietic growth factors regulate differentiation

and proliferation

Erythropoietin – RBCs

Thrombopoietin – platelets

Colony-stimulating factors (CSFs) and interleukins – WBCs


Red Blood Cells/ Erythrocytes

Contain oxygen-carrying protein hemoglobin

Production = destruction with at least 2 million new RBCs per second

Biconcave disc – increases surface area

Strong, flexible plasma membrane

Glycolipids in plasma membrane responsible for ABO and Rh blood groups

Lack nucleus and other organelles No mitochondria – doesn’t use oxygen


Hemoglobin

Globin – 4 polypeptide chains

Heme in each of 4 chains

Iron ion can combine reversibly with one oxygen molecule

Also transports 23% of total carbon dioxide

Combines with amino acids of globin

Nitric oxide (NO) binds to hemoglobin

Releases NO causing vasodilation to improve blood flow

and oxygen delivery


Shapes of RBC and Hemoglobin


Red Blood Cells

RBC life cycle

Live only about 120 days

Cannot synthesize new components – no nucleus

Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen and liver

Breakdown products recycled Globin’s amino acids reused

Iron reused

Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces


Formation and Destruction of RBC’s

Red blood cell

death and

phagocytosis

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

1

Globin

Red blood cell

death and

phagocytosis

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Heme 2

1

Amino

acids

Reused for

protein synthesis Globin

Red blood cell

death and

phagocytosis

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Heme

3

2

1

Amino

acids

Reused for


Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Heme

4

3

2

1

Amino

acids

Reused for


Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Liver

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme

5 4

3

2

1

Amino

acids

Reused for


Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme

6 5 4

3

2

1

Amino

acids

Reused for


Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme Fe3+

7

6 5 4

3

2

1

Amino

acids

Reused for


Circulation for about

120 days

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme Fe3+

8

7

6 5 4

3

2

1

Amino

acids

Reused for



120 days

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme

Biliverdin Bilirubin

Fe3+

9

8

7

6 5 4

3

2

1

Amino

acids

Reused for



120 days

Bilirubin

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme


Fe3+

10

9

8

7

6 5 4

3

2

1

Amino

acids

Reused for


Stercobilin

Bilirubin

Urobilinogen

Feces

Small

intestine


120 days

Bacteria

Bilirubin

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Macrophage in

spleen, liver, or

red bone marrow

Ferritin Heme


Fe3+

12

11 10

9

8

7

6 5 4

3

2

1

Amino

acids

Reused for


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Small

intestine


120 days

Bacteria

Bilirubin

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Kidney

Macrophage in

spleen, liver, or

red bone marrow

Ferritin

Urobilin

Heme


Fe3+

13 12

11 10

9

8

7

6 5 4

3

2

1

Amino

acids

Reused for


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Large

intestine

Small

intestine


120 days

Bacteria

Bilirubin

Red blood cell

death and

phagocytosis

Transferrin

Fe3+

Fe3+ Transferrin

Liver

+ Globin

+ Vitamin B12

+ Erythopoietin

Key:

in blood

in bile

Erythropoiesis in

red bone marrow

Kidney

Macrophage in

spleen, liver, or

red bone marrow

Ferritin

Urobilin

Heme


Fe3+

14

13 12

11 10

9

8

7

6 5 4

3

2

1


Erythropoiesis

Starts in red bone marrow

with proerythroblast

Cell near the end of development ejects nucleus and becomes a reticulocyte

Develop into mature RBC within 1-2 days

Negative feedback balances production with destruction

Controlled condition is amount of oxygen delivery to tissues

Hypoxia stimulates release of erythropoietin


White Blood Cells/ Leukocytes

Have nuclei

Do not contain hemoglobin

Granular or agranular based on staining

highlighting large conspicuous granules

Granular leukocytes

Neutrophils, eosinophils, basophils

Agranular leukocytes

Lymphocytes and monocytes


Types of White Blood Cells


Functions of WBCs

Usually live a few days

Except for lymphocytes – live for months or years

Far less numerous than RBCs

Leukocytosis is a normal protective response to

invaders, strenuous exercise, anesthesia and

surgery

Leukopenia is never beneficial

General function to combat invaders by phagocytosis or immune responses


Emigration of WBCs

Many WBCs leave the bloodstream

Emigration (formerly

diapedesis)

Roll along endothelium

Stick to and then squeeze between

endothelial cells

Precise signals vary for different types of WBCs


WBCs

Neutrophils and macrophages are active

phagocytes

Attracted by chemotaxis

Neutrophils respond most quickly to tissue

damage by bacteria

Uses lysozymes, strong oxidants, defensins

Monocytes take longer to arrive but arrive in

larger numbers and destroy more microbes

Enlarge and differentiate into macrophages


WBCs

Basophila leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation Intensify inflammatory reaction

Involved in hypersensitivity reactions (allergies)

Eosinophils leave capillaries and enter tissue fluid

Release histaminase, phagocytize antigen-antibody complexes and effective against certain parasitic worms


Lymphocytes

Lymphocytes are the major soldiers of the

immune system

B cells – destroying bacteria and inactivating their

toxins

T cells – attack viruses, fungi, transplanted cells, cancer cells and some bacteria

Natural Killer (NK) cells – attack a wide variety of

infectious microbes and certain tumor cells


Platelets/ Thrombocytes

Myeloid stem cells develop eventually into a megakaryocyte

Splinters into 2000-3000 fragments

Each fragment enclosed in a piece of plasma

membrane

Disc-shaped with many vesicles but no nucleus

Help stop blood loss by forming platelet plug

Granules contain blood clot promoting chemicals

Short life span – 5-9 days


Stem cell transplants

Bone marrow transplant

Recipient's red bone marrow replaced entirely by healthy,

noncancerous cells to establish normal blood cell counts

Takes 2-3 weeks to begin producing enough WBCs to fight

off infections

Graft-versus-host-disease – transplanted red bone marrow

may produce T cells that attack host tissues

Cord-blood transplant

Stem cells obtained from umbilical cord shortly before birth

Easily collected and can be stored indefinitely

Less likely to cause graft-versus-host-disease


Hemostasis

Sequence of responses that stops bleeding

3 mechanisms reduce blood loss

1. Vascular spasm

Smooth muscle in artery or arteriole walls contracts

2. Platelet plug formation

Platelets stick to parts of damaged blood vessel, become activated and accumulate large numbers

3. Blood clotting (coagulation)


Platelet Plug Formation

1

Red blood cell

Platelet

Collagen fibers

and damaged

endothelium

Platelet adhesion 1 1

2

Red blood cell

Platelet

Collagen fibers

and damaged

endothelium

Liberated ADP,

serotonin, and

thromboxane A2

Platelet adhesion 1

Platelet release reaction 2

1

2

3

Red blood cell

Platelet

Collagen fibers

and damaged

endothelium

Liberated ADP,

serotonin, and

thromboxane A2

Platelet plug

Platelet adhesion 1

Platelet release reaction 2

Platelet aggregation 3


Blood Clotting

3. Blood clotting

Serum is blood plasma

minus clotting proteins

Clotting – series of

chemical reactions

culminating in formation of

fibrin threads

Clotting (coagulation)

factors – Ca2+, several

inactive enzymes, various

molecules associated with

platelets or released by

damaged tissues


3 Stages of Clotting

1. Extrinsic or intrinsic pathways lead to formation

of prothrombinase

2. Prothrombinase converts prothrombin into thrombin

3. Thrombin converts fibrinogen (soluble) into fibrin

(insoluble) forming the threads of the clot

Tissue trauma

Tissue

factor

(TF)

Blood trauma

Damaged

endothelial cells

expose collagen

fibers

(a) Extrinsic pathway (b) Intrinsic pathway

Activated XII

Ca2+

Damaged

platelets

Ca2+

Platelet

phospholipids

Activated X

Activated

platelets

Activated X

PROTHROMBINASE

Ca2+

V

Ca2+

V

1

Tissue trauma

Tissue

factor

(TF)

Blood trauma

Damaged

endothelial cells

expose collagen

fibers


Activated XII

Ca2+

Damaged

platelets

Ca2+

Platelet

phospholipids

Activated X

Activated

platelets

Activated X

PROTHROMBINASE

Ca2+

V

Ca2+

Prothrombin

(II)

Ca2+

THROMBIN

(c) Common

pathway

V

1

2

+

+

Tissue trauma

Tissue

factor

(TF)

Blood trauma

Damaged

endothelial cells

expose collagen

fibers


Activated XII

Ca2+

Damaged

platelets

Ca2+

Platelet

phospholipids

Activated X

Activated

platelets

Activated X

PROTHROMBINASE

Ca2+

V

Ca2+

Prothrombin

(II)

Ca2+

THROMBIN

Ca2+

Loose fibrin

threads STRENGTHENED

FIBRIN THREADS

Activated XIII

Fibrinogen

(I)

XIII

(c) Common

pathway

V

1

2

3

+

+


Blood Clotting

Extrinsic pathway

Fewer steps then intrinsic and occurs rapidly

Tissue factor (TF) or thromboplastin leaks into the blood

from cells outside (extrinsic to) blood vessels and initiates

formation of prothrombinase

Intrinsic pathway

More complex and slower than extrinsic

Activators are either in direct contact with blood or

contained within (intrinsic to) the blood

Outside tissue damage not needed

Also forms prothrombinase


Blood Clotting: Common pathway

Marked by formation of prothrombinase

Prothrombinase with Ca2+ catalyzes conversion of prothrombin to thrombin

Thrombin with Ca2+ converts soluble fibrinogen

into insoluble fibrin

Thrombin has 2 positive feedback effects

Accelerates formation of prothrombinase

Thrombin activates platelets

Clot formation remains localized because fibrin absorbs

thrombin and clotting factor concentrations are low


Blood Groups and Blood Types

Agglutinogens – surface of RBCs contain

genetically determined assortment of

antigens

Blood group – based on presence or absence

of various antigens

At least 24 blood groups and more than 100

antigens

ABO and Rh


ABO Blood Group

Based on A and B antigens

Type A blood has only antigen A

Type B blood has only antigen B

Type AB blood has antigens A and B

Universal recipients – neither anti-A or anti-B antibodies

Type O blood has neither antigen

Universal donor

Reason for antibodies presence not clear


Antigens and Antibodies of ABO Blood

Types


Hemolytic Disease

Rh blood group

People whose RBCs have the Rh antigen are Rh+

People who lack the Rh antigen are Rh-

Normally, blood plasma does not contain anti-RH antibodies

Hemolytic disease of the newborn (HDN) – if blood from Rh+ fetus contacts Rh-

mother during birth, anti-Rh antibodies made

Affect is on second Rh+ baby


Typing Blood

Single drops of blood are

mixed with different

antisera

Agglutination with an

antisera indicates the

presence of that antigen

on the RBC


End of Chapter 19

Copyright 2009 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein.

Documents

Chapter 19: The Cardiovascular System: The Bloodcpha.tu.edu.iq/images/lec_5_blood.pdf · 1 Red blood cell Platelet Collagen fibers and damaged endothelium 1 Platelet adhesion 2 Liberated