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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
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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
http://www.physioweb.org/blood_cells.html
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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
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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)
http://www.physioweb.org/blood_cells.html
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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
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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
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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)
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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
Collagen fibersand damaged
endothelium
Liberated ADP,serotonin, andthromboxane A2
Platelet adhesion1
Platelet release reaction2
1
2
3
Platelet
Collagen fibersand damaged
endothelium
Liberated ADP,serotonin, andthromboxane A2
Platelet plug
Platelet adhesion1
Platelet release reaction2
Platelet aggregation3
PlateletPlugFormation
(a) Extrinsic pathway (b) Intrinsic pathway
(a) Extrinsic pathway (b) Intrinsic pathway
(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
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
Activated X
Activatedplatelets
Activated X
PROTHROMBINASECa2+
V
Ca2+V
1
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+
V
Ca2+
Prothrombin(II)
Ca2+
THROMBIN
(c) Commonpathway
V
1
2
+
+
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+
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
Damagedendothelial cellsexpose collagenfibers
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
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
Damagedendothelial cellsexpose collagenfibers
(a) Extrinsic pathway (b) Intrinsic pathway
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
Activated X
Activatedplatelets
Activated X
PROTHROMBINASECa2+
V
Ca2+V
1
(a) Extrinsic pathway (b) Intrinsic pathway
(a) Extrinsic pathway (b) Intrinsic pathway
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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
Damagedendothelial cellsexpose collagenfibers
y ( ) p y
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
Activated X
Activatedplatelets
Activated X
PROTHROMBINASECa2+
V
Ca2+V
1
Tissue trauma
Tissuefactor(TF)
Blood trauma
Damagedendothelial cellsexpose collagenfibers
y ( ) p y
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
Activated X
Activatedplatelets
Activated X
PROTHROMBINASECa2+
V
Ca2+
Prothrombin(II)
Ca2+
THROMBIN
(c) Commonpathway
V
1
2
+
+
(a) Extrinsic pathway (b) Intrinsic pathway
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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
Damagedendothelial cellsexpose collagenfibers
Activated XII
Ca2+
Damagedplatelets
Ca2+
Plateletphospholipids
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
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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