The Circulatory The Circulatory SystemSystem

BloodBlood

Anatomy & Physiology IIChapter 13

Circulatory Systemcirculatory system - the heart, blood vessels and

bloodcardiovascular system - the heart and blood vesselshematology – the study of blood functions of circulatory system

◦ transport O2, CO2, nutrients, wastes, hormones

◦ protection limit spread of infection, destroy

microorganisms and cancer cells, and initiates clotting

◦ regulation fluid balance, stabilizes pH of ECF, and

temperature control

Transportation

BloodCarries oxygen to tissuesCarries carbon dioxide from

tissuesTransports nutrients and other

substances to cellsTransports waste products from

cellsCarries hormones to organs

Regulation

Blood

Buffers keep pH of body fluids between 7.35 and 7.45

Substances maintain osmotic pressure to regulate fluid in tissues (fluid balance)

Transports heat generated in muscles to aid in regulation of body temperature

Protection

BloodCarries cells and antibodies of

immune systemCarries factors to protect against

blood loss

Components and General Properties of Blood

adults have 4-6 L of blooda liquid connective tissue

consisting of cells and extracellular matrix◦plasma – matrix of blood a clear, light yellow fluid

◦formed elements - blood cells and cell fragments red blood cells, white blood cells, and

platelets

Components and General Properties of Bloodseven kinds of formed elements

◦erythrocytes - red blood cells (RBCs)◦Platelets - thrombocytes

cell fragments from special cell in bone marrow

◦leukocytes - white blood cells (WBCs) five leukocyte types divided into two

categories:

granulocytes (with granules) neutrophils eosinophils basophils

agranulocytes (without granules) lymphocytes monocytes

Formed Elements of Blood

Neutrophil

Erythrocyte

Eosinophil

Monocyte

Neutrophil

Basophil

Neutrophil

Platelets

Monocyte

Smalllymphocyte

Young (band)neutrophil

Smalllymphocyte

Largelymphocyte

Separating Plasma From Formed Elements of Blood

hematocrit (packed cell vol.)- centrifuge blood to separate components◦erythrocytes are

heaviest and settle first 37% to 52% total volume

(hematocrit)

◦leukocytes and platelets 1% total volume; buffy

coat

◦plasma the remainder of volume 47% - 63%

Centrifuge

Withdrawblood

Plasma(55% of whole blood)

Buffy coat: leukocytesand platelets(<1% of whole blood)

Erythrocytes(45% of whole blood)

Formedelements

Plasma and Plasma Proteins

plasma – liquid portion of blood3 major categories of plasma

proteins◦albumins – smallest and most

abundant◦globulins (antibodies)

provide immune system functions alpha, beta and gamma globulins

◦fibrinogen precursor of fibrin threads that help form

blood clots

Percentages show the relative proportions of the different components of plasma and formed elements.

Composition of Whole BloodComposition of Whole Blood

Blood Plasma

Plasma is 55% of blood

91% water

8% protein

◦ Albumin

◦ Clotting factors

◦ Antibodies

◦ Complement

•1% other materials

–Glucose

–Amino acids

–Lipids

–Electrolytes

–Vitamins

–Hormones

–Wastes

–Drugs

–Dissolved gases

Hemopoiesisadult production of 400 billion platelets, 200

billion RBCs and 10 billion WBCs every dayhemopoiesis – the production of blood,

especially its formed elementshemopoietic tissues produce blood cells

◦yolk sac produces stem cells for first blood cells colonize fetal bone marrow, liver, spleen and

thymus

◦ liver stops producing blood cells at birth

◦spleen remains involved with lymphocyte production

◦ red bone marrow produces all seven formed elements

The Formed ElementsThe Formed Elements

Produced in red bone marrow

Hematopoietic (blood-forming) stem cells can develop into any blood cell

Short-lived tissue cells

Erythrocytes

Red blood cells (RBCs) most numerous

Mature cells anuclearContain hemoglobin

◦Binds to oxygen for transport◦Carries hydrogen ions for buffering◦Carries carbon dioxide for

elimination

Erythrocytes (RBCs)

Erythrocytes (RBCs)Erythrocytes are an example of the

complementarity of structure and function

Structural characteristics contribute to its gas transport function◦Biconcave shape has a huge surface area

relative to volume◦Erythrocytes are more than 97% hemoglobin◦ATP is generated anaerobically, so the

erythrocytes do not consume the oxygen

they transport

Erythrocyte FunctionRBCs are dedicated to respiratory gas

transport

Hb reversibly binds with oxygen and most oxygen in the blood is bound to Hb

Hb is composed of the protein globin, made up of two alpha and two beta chains, each bound to a heme group

Each heme group bears an atom of iron, which can bind to one oxygen molecule

Each Hb molecule can transport four molecules of oxygen

Hemoglobin (Hb) StructureHemoglobin (Hb) Structureeach Hb molecule consists

of:◦ four protein chains – globins ◦ four heme groups

heme groups◦ nonprotein component that

binds O2 to ferrous ion (Fe2+) at its center

◦ Fe is the symbol for ironglobins - four protein chains

◦ two alpha and two beta chains◦ 5% CO2 in blood is bound to

globin moietyadult vs. fetal hemoglobin

(a)

(b)

C

CH3

C

C

C

CC

C

C

CC

CC

N

N

NN

CH

CH

CH

CH

CH2

COOH

CH3 CH3

CH2

CH2

CH2

COOH

CH2 CH3

HC

C

C C

CHC

Fe2+

CH2

Beta

Alpha

Alpha

Beta

Hemegroups

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Erythrocytes and Erythrocytes and HemoglobinHemoglobin

RBC count and hemoglobin concentration indicate amount of O2 blood can carry

◦ hematocrit (packed cell volume) – percentage of whole blood volume composed of red blood cells men 42- 52% cells; women 37- 48% cells

◦ hemoglobin concentration of whole blood higher in men

◦ RBC count higher in men

Why values are lower in women

◦ androgens stimulate RBC production

◦ women have periodic menstrual losses

◦ hematocrit is inversely proportional to percentage of body fat

Hemoglobin (Hb)

Oxyhemoglobin – Hb bound to oxygen◦Oxygen loading takes place in the lungs

Deoxyhemoglobin – Hb after oxygen diffuses into tissues (reduced Hb)

Carbaminohemoglobin – Hb bound to carbon dioxide

◦Carbon dioxide loading takes place in the tissues

Production of ErythrocytesHematopoiesis – blood cell

formationHematopoiesis occurs in the red

bone marrow of the:◦Axial skeleton and girdles

◦Epiphyses of the humerus and femur

Hemocytoblasts give rise to all formed elements

Production of Erythrocytes: Erythropoiesis

Regulation and Requirements for ErythropoiesisCirculating erythrocytes – the number

remains constant and reflects a balance between RBC production and destruction◦Too few RBCs leads to tissue hypoxia

◦Too many RBCs causes undesirable blood viscosity

Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins

Hormonal Control of ErythropoiesisErythropoietin (EPO) release by the

kidneys is triggered by:◦Hypoxia due to decreased RBCs

◦Decreased oxygen availability

◦Increased tissue demand for oxygen

Enhanced erythropoiesis increases the: ◦RBC count in circulating blood

◦Oxygen carrying ability of the blood

Homeostasis: Normal blood oxygen levels

IncreasesO2-carryingability of blood

Erythropoietinstimulates redbone marrow

Reduces O2 levelsin blood

Kidney (and liver to a smallerextent) releases erythropoietin

Enhancederythropoiesisincreases RBC count

Stimulus: Hypoxia due todecreased RBC count,decreased amount of hemoglobin, or decreased availability of O2

Start

Imbalance

Imbalance

Erythropoietin Mechanism

Erythrocyte HomeostasisErythrocyte Homeostasisnegative feedback control

◦ drop in RBC count causes kidney hypoxia

◦ kidney production of EPO stimulates bone marrow

◦ RBC count increases in 3 - 4 days

stimuli for increasing erythropoiesis◦ low levels O2 (hypoxemia)

◦ high altitude◦ increase in exercise◦ loss of lung tissue in

emphysema

leaves

Hypoxemia(inadequate O2 transport)

Sensed by liver and kidneys

Secretion oferythropoietin

Acceleratederythropoiesis

IncreasedRBC count

IncreasedO2 transport

Stimulation ofred bone marrow

Erythrocytes Death and Erythrocytes Death and DisposalDisposalRBCs lyse in narrow channels in spleenmacrophages in spleen

◦digest membrane bits◦separate heme from globin

globins hydrolyzed into amino acids iron removed from heme

heme pigment converted to biliverdin then to bilirubin (yellow)

bilirubin released into blood plasma (kidneys - yellow urine)

liver removes bilirubin and secretes into bile- concentrated in gall bladder: released into small

intestine; bacteria create urobilinogen (brown feces)

Erythrocytes Erythrocytes Recycle/DisposalRecycle/Disposal

Small intestine

GlobinHeme

IronBiliverdin

Bilirubin

Bile

Feces

Storage Reuse Loss bymenstruation,

injury, etc.

Amino acidsIronFolic acidVitamin B12

Nutrientabsorption

Erythrocytescirculate for

120 days

Expired erythrocytesbreak up in liver and spleen

Cell fragmentsphagocytized

Erythropoiesis inred bone marrow

Hemoglobindegraded

Hydrolyzed to freeamino acids

ErythrocyteErythrocyte Disorders Disorderspolycythemia - an excess of RBCs

◦primary polycythemia (polycythemia vera) cancer of erythropoietic cell line in red bone

marrow RBC count as high as 11 million/L; hematocrit 80%

◦secondary polycythemia from dehydration, emphysema, high altitude, or

physical conditioning RBC count up to 8 million/L

dangers of polycythemia◦increased blood volume, pressure, viscosity

can lead to embolism, stroke or heart failure

AnemiaAnemiacauses of anemia fall into three

categories:◦inadequate erythropoiesis or

hemoglobin synthesis kidney failure and insufficient erythropoietin iron-deficiency anemia inadequate vitamin B12 from poor nutrition or

lack of intrinsic factor (pernicious anemia) hypoplastic anemia – slowing of

erythropoiesis aplastic anemia - complete cessation of

erythropoiesis

◦hemorrhagic anemias from bleeding◦hemolytic anemias from RBC destruction

AnemiaAnemiaanemia has three potential

consequences:◦tissue hypoxia and necrosis

patient is lethargic shortness of breath upon exertion life threatening necrosis of brain, heart, or

kidney

◦blood osmolarity is reduced producing tissue edema

◦blood viscosity is low heart races and pressure drops cardiac failure may ensue

Sickle-Cell DiseaseSickle-Cell Diseasehereditary hemoglobin defects

that occur mostly among people of African descent

caused by a recessive allele that modifies the structure of the hemoglobin molecule (HbS)◦ differs only on the sixth amino

acid of the beta chain◦ HbS does not bind oxygen well◦ RBCs become rigid, sticky, pointed

at ends◦ clump together and block small

blood vessels causing intense pain◦ can lead to kidney or heart failure,

stroke, rheumatism or paralysis

7 µm

Blood TypesBlood Typesblood types and transfusion

compatibility are a matter of interactions between plasma proteins and erythrocytes

blood types are based on interactions between antigens and antibodies

Blood Antigens and Blood Antigens and AntibodiesAntibodies

antigens◦complex molecules on surface of cell

membrane that are unique to the individual used to distinguish self from foreign foreign antigens generate an immune

response agglutinogens – antigens on the

surface of the RBC that is the basis for blood typing

Blood Antigens and Blood Antigens and AntibodiesAntibodies

antibodies◦proteins (gamma globulins) secreted by

plasma cells part of immune response to foreign

matter bind to antigens and mark them for

destruction forms antigen-antibody complexes agglutinins – antibodies in the plasma

that bring about transfusion mismatch

Blood TypesBlood Types

RBC antigens called agglutinogens◦called antigen A and

B◦determined by

carbohydrate components found on RBC surface

antibodies called agglutinins◦found in plasma◦anti-A and anti-B

leaves

Type O Type B

Type A Type AB

Galactose

Fucose

N-acetylgalactosamine

Key

ABO GroupABO Group

your ABO blood type is determined by presence or absence of antigens (agglutinogens) on RBCs◦blood type A person has A antigens

◦blood type B person has B antigens

◦blood type AB has both A and B antigens

◦blood type O person has neither antigen most common - type O

rarest - type AB

Plasma AntibodiesPlasma Antibodiesantibodies (agglutinins); anti-A and anti-

Bappear 2-8 months after birth; at

maximum concentration at 10 yr.◦ antibody-A and/or antibody-B (both or none)

are found in plasma you do not form antibodies against your antigens

agglutination ◦ each antibody can attach to several foreign

antigens on several different RBCs at the same time

responsible for mismatched transfusion reaction◦ agglutinated RBCs block small blood vessels,

hemolyze, and release their hemoglobin over the next few hours or days

◦ Hb blocks kidney tubules and causes acute renal failure

Agglutination of Agglutination of ErythrocytesErythrocytes

Antibodies(agglutinins)

Transfusion ReactionTransfusion Reaction

leaves

Blood fromtype A donor

Agglutinated RBCsblock small vessels

Donor RBCsagglutinated byrecipient plasma

Type B(anti-A)recipient

Universal Donors and Universal Donors and RecipientsRecipientsSafest transfusion is same blood typeuniversal donor

◦Type O – most common blood type◦lacks RBC antigens◦donor’s plasma may have both

antibodies against recipient’s RBCs (anti-A and anti-B) may give packed cells (minimal plasma)

universal recipient ◦Type AB – rarest blood type◦lacks plasma antibodies; no anti- A or B

Testing for Blood TypeBlood sera containing antibodies

to A or B antigens (antisera) prepared

Sera added to blood sample

Corresponding red cells clump (agglutination)

Labels on the bottles denote the kind of antiserum (antibodies) added to the blood samples.

Anti-A serum agglutinates (causes to clump) red cells in type A blood, but anti-B serum does not.

Anti-B serum agglutinates red cells in type B blood, but anti-A serum does not. Both sera agglutinate type AB blood cells, and neither serum agglutinates type O blood.

ZOOMING IN • Can you tell from these

reactions whether these cells are Rh positive or Rh negative?

Blood TypingBlood Typing

Type A

Type B

Type AB

Type O

The Rh FactorRed cell antigen group Rh (D antigen)

◦Rh-positive blood has antigen

◦Rh-negative blood lacks antigen

Rh incompatibility can lead to hemolytic disease of newborn (HDN)

Anti-D agglutinins not normally present◦form in Rh- individuals exposed to Rh+ blood

Rh- woman with an Rh+ fetus or transfusion of Rh+ blood

no problems with first transfusion or pregnancy

Hemolytic Disease of Hemolytic Disease of NewbornNewbornoccurs if Rh- mother has formed

antibodies and is pregnant with second Rh+ child◦Anti-D antibodies can cross placenta

prevention◦RhoGAM given to pregnant Rh- women

binds fetal agglutinogens in her blood so she will not form Anti-D antibodies

Hemolytic Disease of Hemolytic Disease of NewbornNewborn

Rh antibodies attack fetal blood causing severe anemia and toxic brain syndrome

leaves

Uterus

Placenta

Rh mother

(a) First pregnancy (b) Between pregnancies (c) Second pregnancy

Rhantigen

Rh+ fetus

Amniotic sacand chorion

Anti-Dantibody

SecondRh+ fetus

LeukocytesLeukocytesWhite blood cells (WBCs) colorless,

round◦Granulocytes

Neutrophils (polymorphs) Eosinophils Basophils

◦Agranulocytes Lymphocytes Monocytes

Prominent nuclei Clear body of foreign material, cellular

debris, pathogens

(A) A phagocytic leukocyte (white blood cell) squeezes through a capillary wall in the region of an infection and engulfs a bacterium.

(B) The bacterium is enclosed in a vesicle and digested by a lysosome.

ZOOMING IN • What type of epithelium makes up the capillary wall?

Phagocytosis Phagocytosis

Components of Whole Blood

Platelets

Platelets (thrombocytes)Smallest formed elementNot cells—no nuclei or DNAFragments release from

megakaryocytesEssential for blood coagulation

(clotting)

HemostasisHemostasisPrevents blood loss when blood

vessel rupturesContraction of smooth muscles in

blood vessel wall (vasoconstriction)

Formation of platelet plugFormation of blood clot

Blood ClottingProcoagulants: compounds that

promote clottingAnticoagulant: compounds that

prevent clottingFinal steps in clotting:

◦Damaged tissues release substances that form prothrombinase

◦Prothrombinase converts prothrombin to thrombin

◦Thrombin converts fibrinogen to fibrin◦Fibrin forms network of threads to

form clot

Blood Clotting (cont’d)Serum: fluid left over after

clotting takes placePlasma = serum + clotting

factors

Coagulation DisordersCoagulation Disordersthrombosis - abnormal clotting in

unbroken vessel

◦thrombus - clot most likely to occur in leg veins of inactive

people

◦ pulmonary embolism - clot may break free, travel from veins to lungs

embolus – anything that can travel in the blood and block blood vessels

infarction (tissue death) may occur if clot blocks blood supply to an organ (MI or stroke)◦ 650,000 Americans die annually of

thromboembolism – traveling blood clots

Properties of Bloodviscosity - resistance of a fluid to flow

◦ whole blood 4.5 - 5.5 times as viscous as water

◦ plasma is 2.0 times as viscous as water important in circulatory function

osmolarity of blood - the total molarity of those dissolved particles that cannot pass through the blood vessel wall◦ if too high, blood absorbs too much water,

increasing the blood pressure◦ if too low, too much water stays in tissue,

blood pressure drops and edema occurs◦ optimum osmolarity is achieved by bodies

regulation of sodium ions, proteins, and red blood cells.

Uses of Blood and Blood Uses of Blood and Blood ComponentsComponentsBlood stored in blood banks up to

35 days

◦Anti-clotting solution added

◦Expiration date added

Blood donated before elective surgery (autologous blood)

Whole Blood Transfusions

Used for loss of large volume of blood

Massive hemorrhage from serious injuries

During internal bleeding

During or after an operation

Blood replacement in treatment of HDN

Use of Blood Components

Centrifuge separates plasma from formed elements

Hemapheresis—keep desired elements and return remainder to donor

Plasmapheresis—keep plasma and return formed elements to donor

Use of PlasmaReplace blood volume

Treat circulatory failure (shock)

Treat plasma protein deficiency

Replace clotting factors

Provide needed antibodies

Blood DisordersBlood Disorders

Blood abnormalitiesAnemia (low level of hemoglobin

or red cells)Leukemia (increase in white cells)Clotting disorders (abnormal

tendency to bleed)

AnemiaAnemia causesExcessive loss or destruction of red

cells◦Hemorrhagic anemia◦Hemolytic anemia◦Sickle cell anemia

Impaired production of red cells or hemoglobin◦Deficiency anemia◦Thalassemia◦Bone marrow suppression

LeukemiaLeukemia is characterized by

enormous increase in white cellsMyelogenous leukemia from bone

marrowLymphocytic leukemia from

lymphoid tissueBone marrow transplants

sometimes successful in restoring blood-producing stem cells lost after leukemia treatment

Clotting Disorders

Abnormal bleeding through disruption of coagulation process

HemophiliaVon Willebrand diseaseThrombocytopeniaDisseminated intravascular

coagulation (DIC)

Blood StudiesBlood StudiesSome blood tests are standard

part of routine physical examination

Machines can perform several tests simultaneously

The HematocritPacked cell volume (% of RBC in

whole blood)

Performed in centrifuge

Adult range for men 42%–54%

Adult range women 36%–46%

Hemoglobin Tests

Mass (in grams) of hemoglobin per 100 mL of whole blood

Performed by electrophoresis

Adult range for men 14–17 g

Adult range for women 12–15 g

Blood Cell CountsRed cell counts

◦Range 4.5–5.5 million cells per microliter (μL)

White cell counts

◦Range 5,000–10,000 cells per microliter (μL)

Platelet counts

◦Range 150,000–450,000 per microliter (μL)

The Blood Slide (Smear)

Complete blood count (CBC) performed on drop stained blood slide

Red cells examined

Platelets examined

Parasites may be found

Differential white count performed

Blood Chemistry TestsBatteries of blood serum tests often

done by machineElectrolytesBlood glucoseNitrogenous waste productsCreatineEnzymesLipidsPlasma proteinsHormonesVitaminsAntibodiesDrug levels

Coagulation StudiesPerformed before surgery and

during treatment of certain diseases

Amounts of clotting factors

Bleeding time

Clotting time

Capillary strength

Platelet function

Bone Marrow BiopsySample of red marrow through

needle from sternum, sacrum, or iliac crest

Used in diagnosing bone marrow disorders

◦Leukemia

◦Some types of anemia

End of Presentation