Chapter 19

The BloodThe Blood

The BloodThe Blood The The cardiovascular systemcardiovascular system consists of consists of

three interrelated components: Blood, the three interrelated components: Blood, the heart, and blood vessels. heart, and blood vessels.

Blood contributes to Blood contributes to homeostasishomeostasis by by transportingtransporting respiratory gasses, respiratory gasses,

nutrients, and hormones to and from your nutrients, and hormones to and from your body’s cells. body’s cells.

It helps It helps regulateregulate body pH and body pH and temperature, temperature,

and provides and provides protectionprotection through its through its clotting mechanisms and immune defensesclotting mechanisms and immune defenses

Physical characteristicsPhysical characteristics Blood is denser and more viscous. Blood is denser and more viscous. The temperature is 100.4The temperature is 100.4ooF.F. Alkaline pH ranging from 7.35 to 7.45.Alkaline pH ranging from 7.35 to 7.45. The color of blood varies with its The color of blood varies with its

oxygen content.oxygen content. The blood volume is 5 to 6 liters in an The blood volume is 5 to 6 liters in an

average adult male and 4 to 5 liters average adult male and 4 to 5 liters in female.in female.

Constituents of BloodConstituents of Blood If a tube of anticoagulated blood is If a tube of anticoagulated blood is

allowed to sit for a period of time, the allowed to sit for a period of time, the cellular portioncellular portion will precipitate out of will precipitate out of solution and form a heavier solution and form a heavier sedimentsediment below the strawbelow the strawcolored liquid plasmacolored liquid plasma–We can speed up the We can speed up the

separation process by separation process by

spinning the tube of spinning the tube of

blood in a centrifugeblood in a centrifuge

Constituents of BloodConstituents of Blood

PlasmaPlasma

Formed ElementsFormed Elements Red blood cells Red blood cells (RBCs)(RBCs) make up the make up the

bulk of the blood cells, with many bulk of the blood cells, with many

fewer white blood cells (WBCs) fewer white blood cells (WBCs)

interspersed in among theminterspersed in among them The normal RBC mass is between 40–45% by volume – this is The normal RBC mass is between 40–45% by volume – this is

called the called the hematocrit (Hct), hematocrit (Hct),

and corresponds and corresponds

to 4–6 to 4–6 xx 10 1066/mm/mm33

by number.by number.

Formed ElementsFormed Elements WBCs,WBCs, by number, make up between by number, make up between

5-10 x 105-10 x 1033/mm/mm3 3 – RBCs outnumbered WBCs by about 700:1RBCs outnumbered WBCs by about 700:1– There are 5 different types of WBCs, all There are 5 different types of WBCs, all

with varying functionswith varying functions

MegakaryocytesMegakaryocytes are huge cells are huge cells

that splinter into 2000 to 3000 that splinter into 2000 to 3000

fragments fragments while still in the red while still in the red

bone marrowbone marrow

– Each fragment, enclosed by a piece Each fragment, enclosed by a piece

of the plasma membrane, is a of the plasma membrane, is a plateletplatelet

Formed ElementsFormed Elements

Formed ElementsFormed Elements PlateletsPlatelets are more numerous than are more numerous than

WBCs (150-400 x 103/mm3 ), but they WBCs (150-400 x 103/mm3 ), but they have a short life span (5 to 9 days) have a short life span (5 to 9 days) and they don’t have much mass. They and they don’t have much mass. They appear as little specks interspersed appear as little specks interspersed among the among the many red cellsmany red cells–Their granules Their granules

contain chemicals that, contain chemicals that, once released, promote once released, promote blood clottingblood clotting

HematopoiesisHematopoiesis The process by which the formed elements of blood The process by which the formed elements of blood

develop is called hemopoiesis develop is called hemopoiesis (hematopoiesis).(hematopoiesis).

In adults, blood cells are formed in red bone In adults, blood cells are formed in red bone

marrow from pluripotent stem cells. marrow from pluripotent stem cells.

They mature They mature

in bone marrow or in bone marrow or

lymphoid tissuelymphoid tissue

Bone marrow harvesting for use in a bone marrow transplant.

HematopoiesisHematopoiesis The pluripotent stem cell at the top of this chart is The pluripotent stem cell at the top of this chart is

the progenitor of all the other red bone marrow the progenitor of all the other red bone marrow

cellscells

ErythropoiesisErythropoiesis ErythropoiesisErythropoiesis is the part of is the part of

hematopoiesis that deals with the hematopoiesis that deals with the production of RBCs. Erythropoiesis production of RBCs. Erythropoiesis increases when states of hypoxia (Oincreases when states of hypoxia (O2 2

deficiency) stimulates the kidneys to deficiency) stimulates the kidneys to release the hormone release the hormone erythropoietin erythropoietin (EPO)(EPO)–EPO circulates to the red EPO circulates to the red

marrow and speeds up the marrow and speeds up the maturation and release of maturation and release of immature red cellsimmature red cells

ReticulocytesReticulocytes The rate of erythropoiesis is measured The rate of erythropoiesis is measured

by the number of immature RBCs by the number of immature RBCs (called (called reticulocytesreticulocytes or “retics”) in or “retics”) in the peripheral circulationthe peripheral circulation

– A low retic count (<.5%) indicates a A low retic count (<.5%) indicates a low rate of erythropoiesis while an low rate of erythropoiesis while an elevated rate (>2%) indicates a high elevated rate (>2%) indicates a high rate of erythropoiesisrate of erythropoiesis

Red Blood CellsRed Blood Cells Red blood cells are bi-concave discs. Red blood cells are bi-concave discs.

Mature Mature RBCsRBCs don't have a nucleus or don't have a nucleus or any protein making machinery and are any protein making machinery and are destined to die in about 120 days. In a destined to die in about 120 days. In a sense they are not really cells, but sense they are not really cells, but remnants of cells with a very specific remnants of cells with a very specific purpose – to purpose – to carry Ocarry O22 to the tissues of to the tissues of the body.the body.

Red Blood CellsRed Blood Cells The characteristic RBC shape The characteristic RBC shape

increases the cell surface area and increases the cell surface area and gives them a high oxygen carrying gives them a high oxygen carrying capacity; because they lack capacity; because they lack mitochondria, they don’t use any of mitochondria, they don’t use any of the oxygen they carrythe oxygen they carry– Their shape also allows them to deform Their shape also allows them to deform

and fit in small capillary beds and fit in small capillary beds

ReticulocytesReticulocytes As cells mature in the bone marrow, they become smaller, As cells mature in the bone marrow, they become smaller,

the nucleus disappears, and the amount of Hgb increasesthe nucleus disappears, and the amount of Hgb increases

Hemoglobin Hemoglobin (Hgb)(Hgb) is a protein is a protein

molecule adapted to carry Omolecule adapted to carry O22 (and CO (and CO22

as well), and each RBC contains 280 as well), and each RBC contains 280

million molecules of Hgb.million molecules of Hgb.

HemoglobinHemoglobin

Abnormalities of Abnormalities of ErythropoiesisErythropoiesis

AnemiaAnemia is a condition of insufficient is a condition of insufficient RBC’s or hemoglobin (quality or RBC’s or hemoglobin (quality or quantity)quantity)

It is most often the result of low iron intake, It is most often the result of low iron intake, hemolysis, autoimmune disease, blood loss, or hemolysis, autoimmune disease, blood loss, or lack of production in the bone marrow lack of production in the bone marrow

PolycythemiaPolycythemia is a condition of excess is a condition of excess number of RBCsnumber of RBCs

It occurs in response to hypoxia (natural “blood It occurs in response to hypoxia (natural “blood doping” is training at high altitude), shots of EPO doping” is training at high altitude), shots of EPO (illegal “doping”), smoking (COPD), or dehydration(illegal “doping”), smoking (COPD), or dehydration

AnemiasAnemias Iron deficiency anemiaIron deficiency anemia is the most is the most

common anemia in the U.S., and common anemia in the U.S., and affects primarily menstruating womenaffects primarily menstruating women– In the United States, 20% of all women of In the United States, 20% of all women of

childbearing age have iron deficiency childbearing age have iron deficiency anemia, compared with only 2% of adult anemia, compared with only 2% of adult menmen

Hemorrhagic anemiaHemorrhagic anemia is the result of is the result of precipitous blood loss, and results in an precipitous blood loss, and results in an equal decrease in Hct, Hgb content, equal decrease in Hct, Hgb content, and RBC countand RBC count

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

anemia, is an autosomal recessive disorder. A anemia, is an autosomal recessive disorder. A

genetic defect in the primary DNA sequence leads genetic defect in the primary DNA sequence leads

to production of a faulty Hgb to production of a faulty Hgb ββ chain, and RBCs chain, and RBCs

that take on a rigid, sickle-shape that take on a rigid, sickle-shape

– Sickling decreases the cells' flexibility and results in a Sickling decreases the cells' flexibility and results in a

variety of complications; life expectancy is shortenedvariety of complications; life expectancy is shortened

RBC Life CycleRBC Life Cycle RBCs live only about 120 days. To RBCs live only about 120 days. To

maintain normal numbers, new mature maintain normal numbers, new mature cells must enter the circulation at the cells must enter the circulation at the astonishing rate of at least 2 astonishing rate of at least 2 million/second, a pace that balances million/second, a pace that balances the equally high rate of RBC the equally high rate of RBC destructiondestruction– Ruptured RBCs are removed from Ruptured RBCs are removed from

circulation and destroyed by fixed circulation and destroyed by fixed phagocytic macrophages in the spleen and phagocytic macrophages in the spleen and liver—the breakdown products are recycled liver—the breakdown products are recycled and used in numerous metabolic processes, and used in numerous metabolic processes, including the formation of new RBCsincluding the formation of new RBCs

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

Breakdown of RBC

LeukocytesLeukocytes Unlike RBCs, white blood cells Unlike RBCs, white blood cells (WBCs)(WBCs) or or

leukocytesleukocytes have nuclei and a full complement of have nuclei and a full complement of

other organelles - but they do not contain the other organelles - but they do not contain the

protein Hgb.protein Hgb.

LeukocytesLeukocytes Leukocytes are divided into Leukocytes are divided into two groupstwo groups depending on depending on

whether they contain conspicuous chemical-filled whether they contain conspicuous chemical-filled

cytoplasmic granules (when stained)cytoplasmic granules (when stained)

– GranulocytesGranulocytes include the neutrophils, eosinophils, include the neutrophils, eosinophils,

and basophilsand basophils

– AgranulocytesAgranulocytes are the monocytes and lymphocytes are the monocytes and lymphocytes

LeukocytesLeukocytes The most numerous WBC in normal blood (60-The most numerous WBC in normal blood (60-

70% of circulating white cells) is the 70% of circulating white cells) is the neutrophil,neutrophil, or polymorphonucleocyte (PMN) or polymorphonucleocyte (PMN)

– PMNs are granulocytes with a pinkish PMNs are granulocytes with a pinkish cytoplasm, and they are one of the two major cytoplasm, and they are one of the two major

phagocytesphagocytes in the body in the bodytheir principal role is to fight their principal role is to fight

bacterial infectionsbacterial infections

LeukocytesLeukocytes Chemicals released by microbes and Chemicals released by microbes and

inflamed tissues attract phagocytes, a inflamed tissues attract phagocytes, a phenomenon called chemotaxis.phenomenon called chemotaxis.– This graphic shows a PMN phagocytizing a This graphic shows a PMN phagocytizing a

microbe for internal microbe for internal digestion and digestion and

destructiondestruction

LeukocytesLeukocytes EosinophilsEosinophils are characterized by their are characterized by their

large red granules large red granules – They are much less numerous than They are much less numerous than

neutrophils (2-4% of circulating WBCs), but neutrophils (2-4% of circulating WBCs), but their numbers increase slightly with their numbers increase slightly with parasitic parasitic infectioninfection they have also been they have also been

associated with the associated with the

development of development of allergiesallergies

LeukocytesLeukocytes BasophilsBasophils are the third type of are the third type of

granulocyte; they contain large, dark granulocyte; they contain large, dark blue, histamine containing granules blue, histamine containing granules – Normally, they are the lowest number of circulating Normally, they are the lowest number of circulating

WBCs (only 0-1%), but they WBCs (only 0-1%), but they have an important have an important role to role to play in the play in the inflammatory responsesinflammatory responses

LeukocytesLeukocytes While While monocytesmonocytes are not granulocytes, they are not granulocytes, they

come from the same immediate precursor cell come from the same immediate precursor cell

as the 3 granulocytes as the 3 granulocytes (the myeloid stem cell)(the myeloid stem cell)

– Along with neutrophils, monocytes are the other major group of Along with neutrophils, monocytes are the other major group of

phagocytic cells. Even though they constitute only 3-8% of the phagocytic cells. Even though they constitute only 3-8% of the

circulating WBCs, they are much morecirculating WBCs, they are much more

numerous in the peripheral, tissues where they numerous in the peripheral, tissues where they

act as act as “fixed” phagocytes.“fixed” phagocytes.

LeukocytesLeukocytes LymphocytesLymphocytes are the last of the 5 are the last of the 5

types of WBCs, and in many ways they types of WBCs, and in many ways they

are quite differentare quite different– Lymphocytes don’t have granules or phagocytize; their Lymphocytes don’t have granules or phagocytize; their

cytoplasm is sparse compared to their very large nucleus, cytoplasm is sparse compared to their very large nucleus,

and they develop from a different precursor stem celland they develop from a different precursor stem cell

– Also, rather than acting as non-Also, rather than acting as non-

specific defenders, lymphocytes specific defenders, lymphocytes

develop as responders to develop as responders to very very

specific foreign antigensspecific foreign antigens

LeukocytesLeukocytes Approximately 20-30% of circulating white cells Approximately 20-30% of circulating white cells

are lymphocytes: an increase above this number are lymphocytes: an increase above this number

is called a lymphocytosis and often represents an is called a lymphocytosis and often represents an

acute viral infection.acute viral infection.

Most lymphocytes continually move among Most lymphocytes continually move among

lymphoid tissues, lymph, and blood, spending lymphoid tissues, lymph, and blood, spending

only a few hours at a time in bloodonly a few hours at a time in blood

–Lymphocytes are the cornerstone Lymphocytes are the cornerstone

of the specific immune responseof the specific immune response

WBC IndicesWBC Indices For diagnostic purposes, physicians For diagnostic purposes, physicians

measure the measure the total numbertotal number of circulating of circulating WBCsWBCs

– A A leukocytosisleukocytosis is any WBC count > is any WBC count > 10,000/mm10,000/mm33, and usually indicate an infectious , and usually indicate an infectious process or a cancer.process or a cancer.

– A A leukopenialeukopenia is any WBC count < 5,000/mmis any WBC count < 5,000/mm33, , and usually indicates a severe disease (AIDS, and usually indicates a severe disease (AIDS, bone marrow failure, severe malnutrition, or bone marrow failure, severe malnutrition, or chemotherapy).chemotherapy).

WBC IndicesWBC Indices To enhance the diagnostic value of a WBC To enhance the diagnostic value of a WBC

count, the percentages of each of the 5 types count, the percentages of each of the 5 types

of WBCs is determined by using a machine to of WBCs is determined by using a machine to

do a statistical analysis of the blood sample. do a statistical analysis of the blood sample.

This is called the This is called the WBC differentialWBC differential

WBC IndicesWBC Indices Shifts in the normal percentagesShifts in the normal percentages of of

circulating WBCs will often point towards a circulating WBCs will often point towards a bacterial infection (elevated percentage of bacterial infection (elevated percentage of neutrophils) or a viral infection (elevated neutrophils) or a viral infection (elevated percentage of lymphocytespercentage of lymphocytes– In this peripheral blood smear In this peripheral blood smear

a patient with lymphocytic a patient with lymphocytic

leukemialeukemia has a WBC >150,000 has a WBC >150,000

and 90% of the WBCs areand 90% of the WBCs are

cancerous lymphocytes!cancerous lymphocytes!

Lymphocytic leukemia.

PlasmaPlasma is the fluid component of the blood is the fluid component of the blood and contains everything in blood except the and contains everything in blood except the formed elements, which, for collection formed elements, which, for collection purposes, have been centrifuged outpurposes, have been centrifuged out– Plasma contains mostly Plasma contains mostly waterwater,, with with electrolyteselectrolytes,,

hormones, proteins, dissolved gasses, and glucose and hormones, proteins, dissolved gasses, and glucose and other nutrientsother nutrients

PlasmaPlasma

Plasma ProteinsPlasma Proteins The major protein in plasma is The major protein in plasma is albuminalbumin; it ; it

also has many clotting proteins, antibodies, also has many clotting proteins, antibodies, and enzymes.and enzymes.

Albumin is synthesized in the liver and Albumin is synthesized in the liver and contributes significantly to the blood contributes significantly to the blood viscosity and the body’s ability to maintain viscosity and the body’s ability to maintain blood pressure.blood pressure.

It also plays an important role as a carrier It also plays an important role as a carrier molecule.molecule.

Plasma ProteinsPlasma Proteins GlobulinsGlobulins, of which there are several , of which there are several

types: types: αα (alpha), (alpha), ββ (beta), and (beta), and δδ (gamma). Globulins control blood (gamma). Globulins control blood osmotic pressure and act as carrier osmotic pressure and act as carrier moleculesmolecules– αα-globulins-globulins carry bilirubin and steroids carry bilirubin and steroids – ββ-- globulinsglobulins carry copper and iron carry copper and iron – δδ-globulins-globulins are immunoglobulins are immunoglobulins

(antibodies) made by activated B (antibodies) made by activated B lymphocytes called plasma cells lymphocytes called plasma cells

HemostasisHemostasis HemostasisHemostasis is a sequence of is a sequence of

responses that stops bleedingresponses that stops bleeding– When blood vessels are damaged or When blood vessels are damaged or

ruptured, the hemostatic response must be ruptured, the hemostatic response must be quick, localized to the region of damage, quick, localized to the region of damage, and carefully controlled in order to be and carefully controlled in order to be effectiveeffective

– Three mechanismsThree mechanisms reduce blood lossreduce blood loss1.1. Vascular spasm Vascular spasm

2.2. Formation of a platelet plug Formation of a platelet plug

3.3. Blood clotting (coagulation)Blood clotting (coagulation)

HemostasisHemostasis1.1. Vascular spasmVascular spasm occurs as damaged blood occurs as damaged blood

vessels constrictvessels constrict

2.2. Platelets adhere to damaged Platelets adhere to damaged

endothelium to form a endothelium to form a

platelet plug.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

Platelet Plug Formation

HemostasisHemostasis3.3. Clotting Clotting (coagulation)(coagulation) is possible is possible

because of the presence of several clotting because of the presence of several clotting

proteins normally dissolved (soluble) in proteins normally dissolved (soluble) in

the blood. There are the blood. There are 2 pathways to 2 pathways to

activate the systemactivate the system

HemostasisHemostasis

The The extrinsic pathwayextrinsic pathway has few has few steps and occurs rapidly, often steps and occurs rapidly, often within seconds, once the protein within seconds, once the protein “tissue factor” “tissue factor” (TF)(TF) leaks into the leaks into the bloodblood

The The intrinsic pathwayintrinsic pathway is more is more complex and occurs more slowly in complex and occurs more slowly in response to damage to response to damage to endothelial cellsendothelial cells or phospholipids or phospholipids released by released by activated platelets.activated platelets.

Both the extrinsic and intrinsic clotting Both the extrinsic and intrinsic clotting pathways converge at a pathways converge at a common common point (pathway) point (pathway) where factor X where factor X becomes activated (Xa)becomes activated (Xa)– In this In this second stage second stage of of

blood clotting prothrombin blood clotting prothrombin

is converted to thrombin is converted to thrombin

which in turn converts which in turn converts

soluble fibrinogen to soluble fibrinogen to

insoluble fibrin threadsinsoluble fibrin threads


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

+

+

Stages of Clotting

The mineral The mineral CaCa22++ plays an important role plays an important role

throughout the clotting system, and many steps throughout the clotting system, and many steps

have positive or negative feedback on various other have positive or negative feedback on various other

steps to propagate the process, yet maintain controlsteps to propagate the process, yet maintain control

Clot retractionClot retraction is the consolidation of the fibrin is the consolidation of the fibrin

clot. As the clot retracts, it pulls the edges of clot. As the clot retracts, it pulls the edges of the the

damaged vessel closer together, damaged vessel closer together,

decreasing the risk of further decreasing the risk of further

damage – new endothelial cells can damage – new endothelial cells can

then repair the vessel liningthen repair the vessel lining


FibrinolysisFibrinolysis Because blood clotting involves amplification and Because blood clotting involves amplification and

positive feedback cycles, a clot has a tendency to positive feedback cycles, a clot has a tendency to

enlarge, creating the potential for impairment of enlarge, creating the potential for impairment of

blood flow through undamaged vessels blood flow through undamaged vessels – The The fibrinolytic systemfibrinolytic system dissolves small, inappropriate clots; it dissolves small, inappropriate clots; it

also dissolves clots at a site of damage once the damage is also dissolves clots at a site of damage once the damage is

repairedrepaired

both body tissues and blood contain substances that can both body tissues and blood contain substances that can

activate plasminogen to become activate plasminogen to become plasmin,plasmin, (the enzyme that (the enzyme that

actively dissolves clots)actively dissolves clots)

Intravascular ClottingIntravascular Clotting Blood clots sometimes form unexpectedly Blood clots sometimes form unexpectedly

within the cardiovascular system. Clotting within the cardiovascular system. Clotting in an unbroken blood vessel (usually a in an unbroken blood vessel (usually a vein) is called vein) is called thrombosis;thrombosis; the clot itself, the clot itself, called a called a thrombusthrombus– Such clots may be initiated by roughened Such clots may be initiated by roughened

endothelial surfaces of a blood vessel resulting endothelial surfaces of a blood vessel resulting from atherosclerosis, trauma, or infectionfrom atherosclerosis, trauma, or infection

Intravascular ClottingIntravascular Clotting Intravascular clots may also form when Intravascular clots may also form when

blood flows too slowly (stasis), allowing blood flows too slowly (stasis), allowing clotting factors to accumulate locally clotting factors to accumulate locally and initiate the coagulation cascadeand initiate the coagulation cascade

Having an undamaged blood vessels Having an undamaged blood vessels with smooth surfaces, good circulation, with smooth surfaces, good circulation, and non-sticky platelets are important and non-sticky platelets are important factors that factors that inhibit thrombosisinhibit thrombosis– administration of anticoagulants and platelet administration of anticoagulants and platelet

inhibiting drugs (aspirin-like drugs) can also hinder inhibiting drugs (aspirin-like drugs) can also hinder thrombus formation or reverse a thrombus that has thrombus formation or reverse a thrombus that has formedformed

Intravascular Intravascular ClottingClotting

A thrombus may become dislodged and be swept A thrombus may become dislodged and be swept

away in the blood. When a blood clot, air bubble, away in the blood. When a blood clot, air bubble,

piece of fat or other debris is transported by the piece of fat or other debris is transported by the

bloodstream, it is called an bloodstream, it is called an embolus.embolus.

Blood ComponentsBlood Components Blood transfusionBlood transfusion is the process of is the process of

transferring blood or blood products transferring blood or blood products from one person to anotherfrom one person to another

Almost all donated blood in the U.S. is Almost all donated blood in the U.S. is separated into its various components separated into its various components to make better use of itto make better use of it– Whole blood is Whole blood is fractionatedfractionated into units of into units of

packed red blood cells (PRBCs), fresh packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and WBCsfrozen plasma (FFP), platelets, and WBCs

– Albumin, coagulation factors, and Albumin, coagulation factors, and antibodies can be individually collectedantibodies can be individually collected

Plasma vs. SerumPlasma vs. Serum

If the liquid part of blood is allowed If the liquid part of blood is allowed to to coagulate it is called coagulate it is called serum -serum - serum is serum is just plasma without the clotting factorsjust plasma without the clotting factors–Serum is stable at room temperature Serum is stable at room temperature

and can be stored on a shelfand can be stored on a shelfit is also used for it is also used for diagnostic testingdiagnostic testing because because it won’t coagulate in the machine it won’t coagulate in the machine

and mess it up!and mess it up!

In transfusion medicine the presence In transfusion medicine the presence or absence of the or absence of the A and B red cell antigens forms the basis of A and B red cell antigens forms the basis of the the ABO blood group systemABO blood group system

Blood GroupsBlood Groups

Another major red cell antigen is the Rh antigen, which 85%

of the population have, and comprises another important

blood grouping

Blood GroupsBlood Groups For reason that are not totally clear, serum For reason that are not totally clear, serum

contains anti-ABO antibodies of a type opposite to contains anti-ABO antibodies of a type opposite to

the ABO antigen on the red cell surfacethe ABO antigen on the red cell surface

– For instance, those with A antigens on their red For instance, those with A antigens on their red

cells have anti-B antibodies in their serumcells have anti-B antibodies in their serum

Blood GroupsBlood Groups By knowing the status of the A antigen, B By knowing the status of the A antigen, B

antigen, and Rh antigen, most of the major antigen, and Rh antigen, most of the major blood incompatibility issues can be avoidedblood incompatibility issues can be avoided

– Type AB individuals are Type AB individuals are “universal “universal recipients”recipients” because they has neither anti-because they has neither anti-A nor anti-B antibodies in their serum that A nor anti-B antibodies in their serum that would destroy transfused RBCswould destroy transfused RBCs

– Type O individuals are Type O individuals are “universal “universal donors”donors” because their RBCs have no because their RBCs have no antigens on the cell surface that can antigens on the cell surface that can potentially react with the recipients serumpotentially react with the recipients serum

Blood GroupsBlood Groups

Blood typingBlood typing for for ABO status is done ABO status is done using single drops using single drops of blood mixed with of blood mixed with different antiseradifferent antisera– AgglutinationAgglutination with with

an antisera indicates an antisera indicates the presence of that the presence of that antigen on the RBCantigen on the RBC

Rh IncompatibilityRh Incompatibility Normally, blood plasma does not contain Normally, blood plasma does not contain

anti-Rh antibodies; individuals whose RBCs anti-Rh antibodies; individuals whose RBCs

have the Rh antigen are said to be have the Rh antigen are said to be RhRh++ while while

those who lack the Rh antigen are those who lack the Rh antigen are RhRh-- – Rh incompatibilityRh incompatibility can cause problems with any can cause problems with any

blood transfusion, so it is screened just as carefully as the blood transfusion, so it is screened just as carefully as the

ABO groupABO group

perhaps the biggest problem with Rh incompatibility, perhaps the biggest problem with Rh incompatibility,

however, involves mother and child in pregnancyhowever, involves mother and child in pregnancy

Rh IncompatibilityRh Incompatibility If blood from an RhIf blood from an Rh++ fetus sensitizes an fetus sensitizes an

RhRh-- mother during birth, anti-Rh mother during birth, anti-Rh antibodies will form in the blood of that antibodies will form in the blood of that woman. During her next pregnancy woman. During her next pregnancy those antibodies can cross the placenta those antibodies can cross the placenta to affect the next babyto affect the next baby– Hemolytic disease of the Hemolytic disease of the

newborn newborn (HDN)(HDN) resultsresults

when an Rhwhen an Rh+ + fetus fetus

develops in the womb develops in the womb

of an Rhof an Rh- - womanwoman

Rh IncompatibilityRh Incompatibility To prevent HDN, mothers who are RhTo prevent HDN, mothers who are Rh--

are given a injection of are given a injection of RhoGAM RhoGAM -- a a commercially produced anti-Rh antibody commercially produced anti-Rh antibody – at various points in her pregnancy– at various points in her pregnancy– The administered RhoGAM destroys any RhThe administered RhoGAM destroys any Rh++

cells from the baby before the mother’s cells from the baby before the mother’s immune system can become sensitized to immune system can become sensitized to them and produce her own anti-Rh antibody. them and produce her own anti-Rh antibody. For this same reason, RhoGAM is given to For this same reason, RhoGAM is given to RhRh-- patients who have abortions or patients who have abortions or miscarriagesmiscarriages

Transfusion ReactionsTransfusion Reactions

In a blood transfusion, if the recipient In a blood transfusion, if the recipient receives the wrong blood type, receives the wrong blood type, antigen-antibody reactions will cause antigen-antibody reactions will cause a rapid destruction a rapid destruction (hemolysis)(hemolysis) of of the donor red blood cellsthe donor red blood cells– Giving the wrong type blood can cause Giving the wrong type blood can cause

the patient to develop a fever, develop the patient to develop a fever, develop serious renal failure, or go into shock. The serious renal failure, or go into shock. The most common cause is most common cause is clerical errorclerical error (i.e. (i.e. the wrong unit of blood being given to the the wrong unit of blood being given to the patient) patient)

Science

Chapter 19