copyright © john wiley & sons, inc. all rights reserved. chapter 19 the blood

Copyright © John Wiley & Sons, Inc. All rights reserved.

Chapter 19

The Blood


The Blood

The cardiovascular system consists of

three components:

Blood

Heart

Blood vessels


Functions of Blood Blood transports:

• oxygen & CO2 between lungs & tissues

• nutrients from the digestive tract

• metabolic wastes- from body to kidneys for elimination

• hormones from endocrine glands to target organs Blood regulates: • body temperature • pH using buffer systems

Blood protects• against blood loss by initiating hemostasis & coagulation• against infection – antibodies, complement proteins,

WBCs


Physical Characteristics of Blood• It is viscous (thick) and more dense than water

• temperature slightly warmer than core body

temperature (T = 38o C)

• slightly alkaline pH (7.35-7.45)

• oxygenated blood bright red,

poorly oxygenated blood dark red

• makes up 8% of body mass

• Blood volume: 5–6 L for males, and 4–5 L for

females


Constituents of Blood Blood is 5 liters of a specialized fluid connective

tissue composed of formed elements (45%)

suspended in a solution called plasma (55%)

If a sample of blood is centrifuged cellular portion

will precipitate out of solution and form a heavier

sediment below the straw colored liquid plasma

The normal RBC mass is almost

45% by volume – this is called the

hematocrit (Hct)


Constituents of Blood


Blood Plasma

Plasma is 92% water, with dissolved solutes: Plasma proteins – produced by the liver• albumin, globulins, fibrinogen

Nitrogenous wastes• urea, uric acid, creatinine

Nutrients –• glucose, fatty acids, amino acids

Electrolytes • sodium, potassium, calcium, chloride, bicarbonate

Respiratory gases • oxygen and carbon dioxide

Hormones Clotting factors If plasma is allowed to coagulate it is called serum -

serum is just plasma without the clotting factors-

used or blood testing


Plasma Proteins Albumin contributes significantly to colloidal osmotic pressure

of blood It also plays an important role as a carrier molecule for

lipid soluble substances e.g. hormones

globulins, of which there are several types:

α-globulins and β- globulins are carrier proteins

δ-globulins are immunoglobulins (antibodies) made

by activated B lymphocytes called plasma cells

Fibrinogen- clotting factor –forms the blood clot


Formed Elements The formed elements of blood include: Erythrocytes ( RBCs)- highest count Leukocytes( WBCs) Platelets Are continuously formed in the bone marrow


Hematopoiesis

The process by which the formed elements of

blood develop is called hemopoiesis

(hematopoiesis).

blood cells are formed in red bone marrow

from pluripotent stem cells.

Red bone marrow:

In adults : bones of axial skeleton, pectoral &

pelvic girdles, heads of humerus & femur

In newborns- all bone marrow is red


Hematopoiesis


Hematopoiesis Blood cells are formed from pluripotent stem cells. The pluripotent stem cells (hemopoietic stem cells)

produce the myeloid stem cell and lymphoid stem cell myeloid stem cell gives rise to: RBCs, platelets,

monocytes, neutrophils, eosinophils, and basophils lymphoid stem cell gives rise to: T lymphocytes, B

lymphocytes, NK cells Regulation of hematopoiesis: Erythropoietin (EPO) regulates RBC formation Thrombopoietin regulates platelet formation Colony stimulating factors & interleukins stimulate WBC

formation


Clinical connection

•Bone marrow examination by bone marrow aspiration or bone marrow biopsy

•For diagnosis of leukemias, anemias

•Site: usually iliac crest of hip bone, sternum


Red Blood Cells

About 5 million RBCs/mm3 of blood Red blood cells are bi-concave discs-

increases the cell surface area- gives them a

high oxygen carrying capacity Mature RBCs don't have a nucleus or any

protein making machinery -die in about 120

days.

specific purpose – to carry O2

to the tissues of the body-

also carry 23 % CO2

• Their shape also allows them to

deform and fit in small capillary beds


Each RBC contains 280 million molecules of Hb

Hemoglobin (Hb) is a protein molecule

adapted to carry O2 (and CO2 as well) A Hgb molecule consists of globin protein

(2 alpha and 2 beta polypeptide chains), each embedding an iron-containing heme group

Oxygen binds to the heme group ( one Hb binds 4 oxygen molecules)CO2 binds to globin proteins

RBCs and Hemoglobin


RBCs RBCs and CO2:

Red blood cells contain the enzyme carbonic

anhydrase

Carbon dioxide diffuses fron tissues into RBCs

It combines with water to form carbonic acid-

H2CO3 which quickly dissociates into hydrogen

ions and bicarbonate ions

70 % of CO2 is transported in blood as

bicarbonate ions which is an important blood

buffer


RBCs Life Cycle Erythropoiesis is the part of hematopoiesis

that deals with the production of RBCs.

Control is by negative feedback

Erythropoiesis increases when states of

hypoxia (O2 deficiency)- stimulates the kidneys

to release the hormone erythropoietin (EPO)

•EPO circulates to the red

marrow and speeds up the

maturation and release of

immature red cells


Some stimulus disrupts

homeostasis by

Oxygen delivery to kid-neys (and other

tissues)

Receptors

Kidney cellsdetect lowoxygen level

Control center

Proerythroblasts inred bone marrowmature more quicklyinto reticulocytes

EffectorsLarger numberof RBCs incirculation

Increased oxygendelivery to tissues

Return to homeostasiswhen oxygen deliveryto kidneys increases tonormal

Increased erythropoietinsecreted into blood

Input

Increased erythropoietinsecreted into blood

Output

Decreasing

Negative feedback

regulation of Erythropoiesis


RBCs Life Cycle As cells mature in the

bone marrow, they

become smaller

• the nucleus is lost

•Most organelles lost

•the amount of Hb

increases

At reticulocyte

stage RBCs are sent

out into the blood

stream


ReticulocytesReticulocytes:

At this stage the RBCs are sent out into the

blood stream

Normally 1-2% of the RBCs in the peripheral

circulation are reticulocytesThe rate of erythropoiesis is measured by the

number of immature RBCs (called reticulocytes or

“retics”) in the peripheral circulation

•A low retic count (<.5%) indicates a low rate of

erythropoiesis while an elevated rate (>2%)

indicates a high rate of erythropoiesis


RBC Life Cycle RBCs live only about 120 days- are destroyed

mainly in spleen

To maintain normal numbers, new cells must enter

the circulation at 2 million/s to balance high rate of

RBC destruction

• Ruptured RBCs are destroyed by macrophages in

the spleen and liver Heme and globin are separated Globin is metabolized into amino acids- released

into the circulation Iron of the heme is salvaged for re-use Heme is degraded to bilirubin


Red blood celldeath andphagocytosis

Key:

in blood

in bile

Macrophage inspleen, liver, orred bone marrow

1

Globin


Key:

in blood

in bile


Heme2

1

Aminoacids

Reused forprotein synthesisGlobin


Key:

in blood

in bile


Heme

3

2

1

Aminoacids



Transferrin

Fe3+

Key:

in blood

in bile


Heme

4

3

2

1

Aminoacids



Transferrin

Fe3+

Liver

Key:

in blood

in bile


FerritinHeme

54

3

2

1

Aminoacids



Transferrin

Fe3+

Fe3+ Transferrin

Liver

Key:

in blood

in bile


FerritinHeme

654

3

2

1

Aminoacids



Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


FerritinHeme Fe3+

7

654

3

2

1

Aminoacids


Circulation for about120 days


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile

Erythropoiesis inred bone marrow


FerritinHeme Fe3+

8

7

654

3

2

1

Aminoacids




Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme

Biliverdin Bilirubin

Fe3+

9

8

7

654

3

2

1

Aminoacids



Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme


Fe3+

10

9

8

7

654

3

2

1

Aminoacids


Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile



FerritinHeme


Fe3+

12

1110

9

8

7

654

3

2

1

Aminoacids


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


Kidney


Ferritin

Urobilin

Heme


Fe3+

13 12

1110

9

8

7

654

3

2

1

Aminoacids


Urine

Stercobilin

Bilirubin

Urobilinogen

Feces

Largeintestine

Smallintestine


Bacteria

Bilirubin


Transferrin

Fe3+

Fe3+ Transferrin

Liver

+Globin

+Vitamin B12

+Erythopoietin

Key:

in blood

in bile


Kidney


Ferritin

Urobilin

Heme


Fe3+

14

13 12

1110

9

8

7

654

3

2

1

RBC Life Cycle


Clinical connections Anemia is a condition of insufficient RBC’s or

hemoglobin (quality or quantity)

It is most often the result of low iron intake,

hemolysis, blood loss, or lack of production

in the bone marrow

Polycythemia is a condition of excess

number of RBCs

It occurs in response to hypoxia, shots of

EPO (illegal “doping”), COPD


Anemias

Iron deficiency anemia is the most common

anemia in the U.S., and affects primarily

menstruating women

• Chronic blood loss is a cause

Hemorrhagic anemia is the result of

precipitous blood loss, and results in an equal

decrease in Hct, Hb content, and RBC count


Anemias Sickle-cell disease (SCD), also called sickle-

cell anemia, is an autosomal recessive

disorder. A genetic defect in the primary DNA

sequence leads to production of a faulty Hb β

chain, and RBCs that take on a rigid, sickle-

shape

• Sickling decreases the cells' flexibility and

results in a variety of complications; life

expectancy is shortened


White Blood Cells WBCs number- between 5000-10,000 cells/mm3

There are 5 different types of WBCs

(WBCs) or leukocytes have nuclei and other

organelles


Leukocytes Leukocytes are divided into two groups

depending on whether they contain

conspicuous cytoplasmic granules (when

stained)

• Granulocytes include the neutrophils,

eosinophils, and basophils

• Agranulocytes are the monocytes and

lymphocytes


Neutrophils The most numerous WBC in normal blood (60-

70% )is the neutrophil, or

polymorphonucleocyte (PMN)

• PMNs are granulocytes lilac granules and nuclei

have 2-5 lobes

• They are phagocytes - their principal role is to

fight bacterial infectionsPMN phagocytizing

a microbe


Eosinophils Eosinophils are characterized by their large

red granules and bilobed nuclei

They are (2-4% of circulating WBCs), but their

numbers increase slightly with allergic

reactions & parasitic infections

they have also been associated with

the development of allergies


Basophils Basophils are the granulocytes that contain

large, dark blue, histamine containing granules

Normally, they are the lowest number of

circulating WBCs (only 0-1%),

May have a role to play in the

inflammatory responses


Monocytes While monocytes are not granulocytes, they

come from the same immediate precursor cell

as the 3 granulocytes (the myeloid stem

cell)

3-8% of the circulating WBCs

• Along with neutrophils, monocytes are the

other major group of phagocytic cells.

• they are more numerous in

the peripheral, tissues where they

act as “fixed” phagocytes


Lymphocytes Approximately 20-30% of circulating WBCs

are lymphocytes

increase in number in acute viral

infections

Most lymphocytes continually move between

lymphoid tissues, lymph, and blood, spending

only a few hours in blood

Lymphocytes are the cornerstone of the

specific immune response There are two types of lymphocytes: T cells

and B cells•T cells control immune responses •B cells give rise to plasma cells, which produce antibodies


Functions of Leukocytes To get rid of pathogens the WBCs have to leave the

blood stream and collect at sites of infection or injury

WBCs leave the bllod vessels by the process called

emigration :

Rolling along the endothelium & then sticking- by

complementary adhesion molecules on endothelium

(selectins) and on leucocytes (integrins )

Squeeze out between endothelial cells -diapedesis

Chemicals released by microbes and inflamed

tissues attract phagocytes, a phenomenon called

chemotaxis


Functions of Leukocytes Neutrophils are the first to emigrate in bacterial

infections

Reach by chemotaxis & engulf pathogen by phagocytosis

Release strong oxidants & defensins to destroy engulfed

bacteria

Neutrophils are followed by monocytes- which get

transformed into phagocytic tissue macrophages

Lymphocytes take part in immune responses

B cells- antobody mediated humoral immunity

T cells – immune regulation & destruction of viral infected

and cancer cells


Interstitial fluid

Neutrophil

Endothelial cell

Rolling

Sticking

Squeezing betweenendothelial cells

Key:Selectins onendothelial cells

Integrins onneutrophil

Blood flowBlood flow

Emigrationof neutrophils


From Wikimedia Commons

Diapedesis

Chemotaxis & phagocytosis


WBC Indices For diagnostic purposes, physicians measure the total leucocyte count

• A leukocytosis is any WBC count > 10,000/mm3, and usually indicate an

infectious process or inflammation

• A leukopenia is any WBC count < 5,000/mm3, and usually indicates a severe

disease (AIDS, bone marrow failure, severe malnutrition, or chemotherapy)

• Differential leucocyte count : percentages of each of the 5 types of WBCs


WBC Indices

Shifts in the normal percentages of circulating

WBCs will often point towards a bacterial infection

(elevated neutrophils) or a viral infection (elevated

lymphocytes)

• In this peripheral blood smear

a patient with lymphocytic

leukemia has a WBC >150,000

and 90% of the WBCs are

cancerous lymphocytes! Lymphocytic leukemia.


Platelets Platelets (thrombocytes) are about 150,000-

400,000 cells/mm3 , they have a short life span (5

to 9 days)

Their granules contain chemicals

(serotonin, Ca2+, ADP) that,

once released, promote

blood clotting

Also release PDGF-

promotes growth & healing

of damaged vessels


Megakaryocytes (immediate precursors of

platelets) are huge cells that splinter into

2000 to 3000 fragments while still in the

red bone marrow

• Each disc shaped fragment is a platelet

• Platelets leave the red bone marrow

and enter the circulation

Platelets


Hemostasis

Hemostasis is a sequence of responses that

stops bleeding when blood vessels are

damaged or ruptured

• Three mechanisms reduce blood loss

1. Vascular spasm

2. Formation of a platelet plug

3. Blood clotting (coagulation)


Hemostasis1. Vascular spasm occurs as damaged blood

vessels constrict- (by neural & chemical stimuli)

2. Platelets adhere to damaged

endothelium to form a

platelet plug


1

Red blood cell

Platelet

Collagen fibersand damagedendothelium

Platelet adhesion11

2

Red blood cell

Platelet


Liberated ADP,serotonin, andthromboxane A2

Platelet adhesion1

Platelet release reaction2

1

2

3

Red blood cell

Platelet


Liberated ADP,serotonin, andthromboxane A2

Platelet plug

Platelet adhesion1

Platelet release reaction2

Platelet aggregation3

2.Platelet Plug Formation


Hemostasis3. Clotting (coagulation) is possible because of the

presence of several clotting proteins normally

dissolved in the blood in inactive state

Coagulation occurs in a cascade whereby one

activated clotting protein triggers the next step in

the process, which triggers the next

• There are 2 pathways to

activate the clotting cascade:

extrinsic & intrinsic


Tissue trauma

Tissuefactor(TF)

Blood trauma

Damagedendothelial cellsexpose collagenfibers

(a) Extrinsic pathway (b) Intrinsic pathway

Activated XII

Ca2+

Damagedplatelets

Ca2+

Plateletphospholipids

Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

VCa2+

V

1

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

VCa2+

Prothrombin(II)

Ca2+

THROMBIN

(c) Common pathway

V

1

2

+

+

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

VCa2+

Prothrombin(II)

Ca2+

THROMBIN

Ca2+

Loose fibrinthreads

STRENGTHENEDFIBRIN THREADS

Activated XIIIFibrinogen(I)

XIII

(c) Common pathway

V

1

2

3

+

+

Blood clotting cascade


Hemostasis The extrinsic pathway has few

steps, occurs within seconds,

once the protein “tissue factor”

(TF) or tissue thromboplastin

leaks into the blood from cells

The intrinsic pathway is more

complex, & slower in response

blood contact with collagen under

endothelial cells- activates

factor XII


Both the extrinsic and intrinsic clotting

pathways converge at a common

point (pathway) where factor X

becomes activated (Xa), combines with

factor V to form:

• Prothrombin

activator(prothombokinase)

• Prothrombin is converted into

thrombin

• Thrombin converts soluble fibrinogen

into insoluble fibrin threads,

Hemostasis


Ca2+ plays an important role throughout the

clotting system

Clot retraction is the consolidation of the fibrin

clot.

Fibrin threads contract as platelets pull on them

As the clot retracts, it pulls the edges of

the damaged vessel closer together,

decreasing the risk of further

damage – new endothelial cells can

then repair the vessel lining

Hemostasis


Fibrinolysis

Because blood clotting involves positive

feedback cycles, a clot has a tendency to

enlarge, this is checked by:

• The fibrinolytic system - dissolves clots

• Vessel endothelial cells release tissue

plasminogen activator ( tPA) that can

activate plasminogen an inactive plasma

enzyme to become plasmin, (the enzyme

that actively dissolves clots)


Intravascular Clotting Inappropriate clotting in an unbroken blood vessel is

called thrombosis; the clot itself, called a thrombus

• Such clots may be initiated by:

• endothelial injury resulting from atherosclerosis,

trauma, or infection

• Stasis of blood- allowing clotting factors to

accumulate locally and initiate the coagulation

cascade


Intravascular Clotting A thrombus may become dislodged and be

swept away in the blood

blood clot transported

by the bloodstream is

called an embolusemboli can obstruct a

blood vessel and cause ischemia to

the tissue beds e.g. pulmonary embolism,

stroke


Blood Groups

Red cells have antigens or agglutinogens

on their surface These antigens are:• Unique to the individual • Recognized as foreign if transfused into

another individual Presence or absence of these antigens is used

to classify blood groups Major blood group antigens are A and B

antigens & Rh antigen The major blood groups are ABO & Rh blood

groups


In transfusion medicine the presence or absence of the

A and B red cell antigens forms the basis of the ABO

blood group system

Blood Groups

Another major red cell antigen is the Rh

antigen, which 85% of the population have,

and comprises the other important blood

grouping


Blood Groups For reason that are not totally clear, serum

contains anti-ABO antibodies of a type opposite to the ABO antigen on the red cell surface• For instance, those with A antigens on their

red cells have anti-B antibodies in their serum


Blood Groups

By knowing the status of the A antigen, B antigen, and

Rh antigen, most of the major blood incompatibility

issues can be avoided

• Type AB individuals are “universal recipients”

because they has neither anti-A nor anti-B antibodies

in their serum that would destroy transfused RBCs

• Type O individuals are “universal donors” because

their RBCs have no antigens on the cell surface that

can potentially react with the recipients serum


Rh Incompatibility

Individuals whose RBCs have the Rh antigen are

said to be Rh+ while those who lack the Rh

antigen are Rh-

Unlike ABO blood groups, anti-Rh antibodies are

not spontaneously formed in Rh– individuals

If an Rh– individual is exposed to Rh+ blood, anti-

Rh antibodies form( e.g. receiving Rh+

transfusion)

A second exposure to Rh+ blood will result in a

transfusion reaction


Hemolytic Disease of the Newborn

Rh– mother carries a Rh+ fetus At the time of birth she gets

exposed to Rh+ blood- anti RH antibodies are formed

In a subsequent pregnancy, these Rh+ antibodies cross the placenta and attack the RBCs of a Rh+ baby

Results in hemolyis of babys RBCs- baby is born with severe anemia

Prevention- RhoGAM given to Rh– mother ( during pregnancy & at birth)

RhoGAM destroys any Rh+ cells before the mother’s immune system can produce

anti-Rh antibody


Blood Typing & Cross Matching Blood typing for ABO status is done

using single drops of blood mixed with

different antisera:

Anti-A serum contains anti-A antibodies

Anti-B serum contains anti-B antibodies

Agglutination with an antisera

indicates the presence of that antigen

on the RBC

Rh typing: a drop of blood mixed with

antiserum containing anti- Rh

antibodies

Cross matching: RBCs of donors blood

of same type mixed with recipients

serum- checked for agglutination


Transfusion Reactions

Mismatched transfusions cause transfusion reactions

Donor’s cells are attacked by the recipient’s plasma

antibodies causing agglutination & hemolysis :

• Clumped cells block small blood vessels & hemolyse

• Ruptured RBCs release free hemoglobin into the

bloodstream

• Free hemoglobin can block kidneys tubules and

cause acute renal failure

• Person can go into shock

•

copyright © john wiley & sons, inc. all rights reserved. chapter 19 the blood

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