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Chapter 19

Cardiovascular System: The Blood

Hematology

Cells immersed in body fluids: Blood

- Plasma

- Formed elements (cells)

Interstitial fluid

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Functions of Blood

Transportation

Regulation

pH body temp H2O content of cells BP

Protection Blood loss Immunity

http://encarta.msn.com/media_461557603_761578429_-1_1/Lymphocyte.html

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Physical Characteristics of Blood

Avg volume

Consistency

Color

Temperature pH ~7.4

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Blood SamplingPhlebotomy

Venipuncture (mostcommon)

Arterial stick

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Blood SamplingPhlebotomy

Finger or heel stick

Capillary sample

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Components of Blood: Plasma

>90% water ~7% proteins: albumin, fibrinogen, globulins(immunoglobulins)

~2% other solutes: electrolytes, nutrients, gases,hormones, wastes

http://encarta.msn.com/media_461557603_761578429_-1_1/Lymphocy

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Components ofBlood:Formed Elements

RBC (erythrocyte)

WBC (leukocyte)

Granular leukocytes

- neutrophil, eosinophil,basophil

Agranular leukocytes

- lymphocyte = T, B &NK cell, monocyte

Platelet(thrombocyte)

megakaryocyte

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Hematopoiesis (Hemopoiesis)

Embryo

Fetus

Adult

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Stages of Hematopoiesis

Pluripotenthematopoietic stemcell

Myeloid stem cells Progenitor cells (CFU)

Erythroblast reticulocyte RBC

Megakaryocyte thrombocyte

Granulocytes (PMN,basophil, eosinophil)

Monocytemacrophage

Dendritic cell

Lymphoid stem cells T, B & NK cells

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Hemopoietic Growth Factors

Regulatedifferentiation &proliferation

Erythropoietin (EPO)

Thrombopoietin(TPO)

Cytokines

- colony-stimulatingfactor (CSF)

- interleukin (IL)

Recombinant DNAadvances

Growth factor

production

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Red Blood Cells or Erythrocytes

Biconcave disk Increases surface area:volume ratio

Spectrin flexible protein

Anucleate amitotic

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Hemoglobin: Structure & Fxn

Globin protein consists of 4 polypeptides (2a2b) 1 heme attached to each polypeptide heme contains iron

binds 1 oxygen

Oxyhemoglobin

Deoxyhemoglobin

Carbaminohemoglobin

Myoglobin

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HgB: Blood Pressure Regulation?

HgB helps regulate nitric oxide (NO)

When released NO induces vasodilation

NO released from endothelial cells

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Clinical Application: Abnormal HgB

Thalassemia absent orfaulty globin chain in HgB

Sx Tx
http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/radio/images/Large/201B.JPG&template=izoom2http://www.emedicine.com/cgi-bin/foxweb.exe/makezoom@/em/makezoom?picture=/websites/emedicine/radio/images/Large/245I.JPG&template=izoom2

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Clinical Application: Abnormal HgB

Sickle-cell anemia Defective HgB gene (HbS)

RBCs become sickle-shapedin low oxygen situations

Cause anemia, ischemia &infarctionhttp://www.nlm.nih.gov/medlineplus/ency/imagepages/1223.htm

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Erythropoiesis: Production of RBC

Requires protein, lipids, CHO, iron, vB12, folicacid

Three phases in developmental pathway

Reticulocyte Erythrocyte

- Diagnostic test

Copyright 2004 Pearson Education, Inc., publishing as Benjamin Cummings

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Total Erythrocytes (RBC)

Circulatingerythrocytes

# remains constant

Normal RBC count- male 5.4 million/drop

- female 4.8million/drop

Reticulocytes Should be ~1% ofcirculating RBCs

http://www.nlm.nih.gov/medlineplus/ency/imagepages/1491.htm

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Hematocrit

% blood occupied by RBC

female normal range - 38 - 46%

male normal range - 40 - 54%

http://scienceu.fsu.edu/content/virtuallab/hematology/docs/hematocrit.html

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Erythropoietin Mechanism

Reduces O2levels in blood

Erythropoietinstimulates redbone marrowEnhancederythropoiesis

increases RBC

count

Normal blood oxygen levels Stimulus: Hypoxia due todecreased RBC count,decreased availability of O2to blood, or increased

tissue demands for O2

Start

Kidney (and liver to asmaller extent) releaseserythropoietin

IncreasesO2-carryingability of blood

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Erythrocyte Disorders

Polycythemia

Blood doping Induced polycythemia

recEPO or injectingpreviously stored RBCsbefore an athletic event

- more cells available todeliver oxygen to tissues

Dangerous- increases blood viscosity- forces heart to work

harder

- banned by Olympiccommittee

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Anemia: Low O2 -carrying capacity

General signs/Sx

Types of anemia:

Hemorrhagic anemia

Hemolytic anemia

Aplastic anemia

Iron-deficiency anemia

Pernicious anemia

Fig 1. Normal bone marrow. 30-70% of

marrow space consists of hematopoeiticcells w/ remainder being fat.

Fig 2. Patient's bone marrowbiopsy w/ almost noidentifiable hematopoeisis.

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White Blood Cells/ Leukocytes

Complete blood cells

Far less numerous thanRBCs

Usually live a few days

Except for lymphocytes live for months or

years

Leukocytosis

Leukopenia

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Leukocyte Functions:

Inflammation & fightinfection

Emigration

Chemotaxis Diapedesis

- Adhesion molecules(Selectins & integrins)

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Classification of Leukocytes

Granulocytes

neutrophils, eosinophils, basophils,dendritic cells

Agranulocytes monocytes (mf) or lymphocytes

http://encarta.msn.com/media_461557603_761578429_-1_1/Lymphocyte.html

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Neutrophils: Polymorphonuclear leukocytes

Aka: PMN, Segs,Polys

60-70% of circulatingWBCs

Multi-lobed nuclei

Granules = peroxidases,hydrolytic enz &defensins

Band (shift)

Functions

targetbacteria Lysozymes Defensin proteins Strong oxidants Phagocytosis

http://cal.vet.upenn.edu/histo/mammalblood/felbandneutbas.htm

http://www.physioweb.org/blood_cells.html

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Eosinophils (Granulocyte)

~1-4% circulating WBC

Nucleus w/ 2-3 lobes

Large, uniform-sized

granules stain orange-

red w/ acidic dyes

Functions

Release histaminase

Phagocytize Ab-Agcomplexes

Attack parasitic worms

http://greenfield.fortunecity.com/rattler/46/blood.htm


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Basophils (Granulocyte)

< 1% of circulating WBC Large, dark purple, variable-

sized granules

Histamine

Irregular, s-shaped, bilobednuclei

Functions Leave capillaries & enter CT

Release heparin, histamine &serotonin

Intensify the inflammatory &allergy rxn

- Involved with hypersensitivity rxns

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Identify these cells:

Basophil

PMN

Eosinophil

RBC
http://www.nursing.ucla.edu/Userpages/mwoo/cbc/_vti_bin/shtml.exe/smear.htm/map

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Monocyte (Agranulocyte)

3-8% of circulating WBCs

Physical features

U or kidney shaped nucleus

Migratory

Differentiate into macrophage (mf)

- Fixed mf

- Free (wandering) mf

Phagocytes

Antigen presenting cell (APC) viaMHC (major histocompatibilitycomplex)


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Lymphocyte (Agranulocyte)

General features ~25% of circulating

WBCs

Dark, oval to roundnucleus

Types of lymphocytes NK cells (Innate)

- Viral infected & tumorcells

B cells (plasma)

- Make antibody toantigens

T cells- virus, fungi, cancer,

some bacteria,transplants

http://greenfield.fortunecity.com/rattler/46/blood.htm

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Clinical Application: Leukemia

Acute leukemia

uncontrolledproduction ofimmature leukocytes

Chronic leukemia

accumulation of

mature WBC inbloodstream becausethey do not die

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Bone Marrow Transplant

Procedure donor match (MHC)

destroy sick bone marrow

IV transfer of healthy bone

marrow Risky business!

Tx used for leukemia,sickle-cell, breast, ovarianor testicular cancer,

lymphoma or aplasticanemia

- Regimen-related toxicities

- Infection

- Graft versus host
http://en.wikipedia.org/wiki/Image:Bone_marrow_biopsy.jpg

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Another option?

Cord blood transplant

More Tolerant Matching

More Quickly Available

Less Graft-Versus-HostDisease

Stem cells taken from

umbilical cord & frozen -painless
http://en.wikipedia.org/wiki/Image:Umbilicalcord.jpg

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Platelet (Thrombocyte) Anatomy

Cell fragment (anucleate) Formed in bone marrow Myeloid stem cell

megakaryoblastmegakaryocyte fragments = platelets

Thrombopoietin

Short life span Old cells removed by fixed mf in

liver & spleen

Function in hemostasis Blood clotting (plug)
http://en.wikipedia.org/wiki/Image:SEM_blood_cells.jpg

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Total platelet count

Normal count 150-400K platelets

in each cc blood

Thrombocytopenia

Purpuric spots

- petechiae

- ecchymoses

Thrombocythemia(Thrombocytosis)

http://www.emedicine.com/med/topic987.htm

http://www.healthsystem.virginia.edu/internet/hematology/hessidb/Platelet-Disorders.c

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Hemostasis

Quick stoppage of bleedingin localized area

Prevents hemorrhage

Rapid sequence of events:

1. Vascular spasm

(Vasoconstriction)

2. Platelet plug formation

(Primary hemostasis)

3. Coagulation (Secondary

hemostasis)

Red blood cell

Red blood cell

Red blood cell

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1

Platelet

Collagen fibersand damaged

endothelium

Platelet adhesion11

2

Platelet


endothelium

Liberated ADP,serotonin, andthromboxane A2

Platelet adhesion1

Platelet release reaction2

1

2

3

Platelet


endothelium

Liberated ADP,serotonin, andthromboxane A2

Platelet plug

Platelet adhesion1

Platelet release reaction2

Platelet aggregation3

PlateletPlugFormation

(a) Extrinsic pathway (b) Intrinsic pathway



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Stages of Clotting:

Clot = Fibrin + trapped RBC Clotting factors

Involves three stages:

1. Formation of prothrombinase2. Convert prothrombin thrombin

3. Convert fibrinogen fibrin

Two Pathways:

Contact Activation pathway(formerly Intrinsic Pathway)

Tissue Factor pathway (formerlyExtrinsic pathway)

Tissue trauma

Tissuefactor(TF)

Blood trauma

Damagedendothelial cellsexpose collagenfibers


Activated XII

Ca2+

Damagedplatelets

Ca2+

Plateletphospholipids

Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+V

1

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+

Prothrombin(II)

Ca2+

THROMBIN

(c) Commonpathway

V

1

2

+

+

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+

Prothrombin(II)

Ca2+

THROMBIN

Ca2+

Loose fibrinthreads

STRENGTHENEDFIBRIN THREADS

Activated XIII

Fibrinogen(I)

XIII

(c) Commonpathway

V

1

2

3

+

+

Extrinsic Pathway

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Extrinsic Pathway(Tissue Factor Pathway)

Formation of

prothrombinase

Damaged tissue leaks

tissue factor(thromboplastin)

Add in Ca2+ + Factor V/X

Produce prothrombinase

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+V

1

Intrinsic Pathway

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Intrinsic Pathway(Contact Activation)

Activation (endothelium

damaged)

Platelets bind collagen

Activated platelets release

phospholipids

Ca+2 + factors XII

activation of factors X & V prothrombinase

Tissue trauma

Tissuefactor(TF)

Blood trauma



Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+V

1



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Common Pathway

Prothrombinase + Ca+2 Converts prothrombin

thrombin

Thrombin + Ca+2 + XIIIaconverts fibrinogen toinsoluble fibrin

Positive feedbackmechanism

Accelerates formation ofprothrombinase

Activates platelets torelease phospholipids

Tissue trauma

Tissuefactor(TF)

Blood trauma


y ( ) p y

Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+V

1

Tissue trauma

Tissuefactor(TF)

Blood trauma


y ( ) p y

Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+

Prothrombin(II)

Ca2+

THROMBIN

(c) Commonpathway

V

1

2

+

+


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Blood Clotting

Serum blood plasma

w/o clottingproteins

Clotting

series ofchemical rxns formation offibrin threads

Clotting factors Ca+2, inactive

enzymes, &variousmoleculesassociated w/platelets orreleased bydamaged

tissues

Tissue trauma

Tissuefactor(TF)

Blood trauma


Activated XII

Ca2+

Damagedplatelets

Ca2+


Activated X

Activatedplatelets

Activated X

PROTHROMBINASECa2+

V

Ca2+

Prothrombin(II)

Ca2+

THROMBIN

Ca2+

Loose fibrinthreads

STRENGTHENEDFIBRIN THREADS

Activated XIII

Fibrinogen(I)

XIII

(c) Commonpathway

V

1

2

3

+

+

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Clot retraction Fibrinolysis

Inactive plasminogen

plasmin Activation requires factor XI, XII & thrombin Plasmin digests fibrin threads

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Intravascular Clotting

Thrombosis (thrombus) Blockage of vessel ischemia &

necrosis

Embolus http://www-medlib.med.utah.edu/WebPath/ATHH

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Anticoagulants

Oral anticoagulantsantagonize effects of Vit K

- Warfarin (Coumadin)

Heparin blocks thrombin

formation- In vivo & in vitro

Low dose aspirin (anti-prostaglandin)

- Blocks synthesis ofthromboxane A2- Inhibits vasoconstriction &

platelet aggregation

- 75 or 81mg Baby aspirin

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Thrombolytic agents

Thrombolyticagents

Dissolve clots

Common drugs

tPA tissue

plasminogenactivator

streptokinase

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Clinical Application: Hemophilia

Inherited deficiencyof clotting factors

bleedingspontaneously orafter minor trauma

Treatment

Transfusions Clotting factors

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Blood Groups and Blood Types

Geneticallydetermined

Categorized intoblood groups based

on presence/absence of antigens

Major blood groups =ABO & Rh groups

Other blood groupsinclude Lewis, Kell,Kidd & Duffysystems

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RH blood groups

Discovered inRhesus monkeyblood

Rh+

vs Rh-

Normal plasmacontains no anti-RhAb

Transfusion rxnupon 2nd exposure hemolysis ofRBCs

http://www.biologymad.com/master.html?http://www.biologymad.com/Immunology/Immunology.htm

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ABO Blood System

Plasma containsisoantibodies

(agglutinins) to

A, B or Rh Ag not

found in yourblood

Transfusion

reactions http://www.biologymad.com/master.html?http://www.biologymad.com/Immunology/Immunology.htm

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Transfusion & Transfusion Reactions

Transfusion

Incompatible bloodtransfusions

Incompatibilitybetween donor &recipient

Causes:

- Agglutinationi. Ag-Ab complexes

- Donated RBCs lysis

- Renal failure

http://www.nobel.se/medicine/educational/landsteiner/readmore.html
http://www.kumc.edu/instruction/medicine/pathology/ed/ch_20a/c20a_s45.jpg

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Hemolytic Disease of Newborn

Rh- mom &Rh+ fetus

First

pregnancy =sensitization

Subsequent

pregnancy =

reaction

RhoGAM

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Typing and Cross-Matching Blood

Blood typing

Agglutination (Ab

+ Ag)

Cross-matching

Screening

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Universal Donors and Recipients

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