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Chapter 18 Cardiovascular System: Blood
Hematology
Cells immersed in body fluids:• Blood
- Plasma - Formed elements (cells)
• Interstitial fluid
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Functions of Blood
Transportation
Regulation• Body pH• body temp• Fluid balance
- 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
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Components of Blood
Centrifuge
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Com
pone
nts
of B
lood
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Components of Blood: Plasma
>90% water ~7% proteins: albumin,
fibrinogen, globulins (immunoglobulins)
~2% other solutes: electrolytes, nutrients, gases, hormones, wastes
Common Electrolytes in Plasma
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Common Nutrients in Plasma
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Components of Blood: Formed Elements
RBC (erythrocyte) WBC (leukocyte)
• Granular leukocytes- neutrophil,
eosinophil, basophil
• Agranular leukocytes - lymphocyte = T, B
& NK cell, monocyte
Platelet (thrombocyte)
• megakaryocyteBlood Smear
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Stages of Hematopoiesis--Pluripotent hematopoietic stem cell=hemocytoblast
--Myeloid stem cells-Erythroblast reticulocyte RBC
-Megakaryoblast megakaryocyte proplatelet platelet
-Granulocytes (PMN, basophil, eosinophil)
-Monocyte macrophage
--Lymphoid stem cells-T, B & NK cells
Thrombopoiesis
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Hemopoietic Growth Factors
Regulate differentiation & proliferation
• Erythropoietin (EPO)• Thrombopoietin
(TPO)• Cytokines
- colony-stimulating factor (CSF)
- interleukin (IL)
Recombinant DNA advances
• Growth factor production
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Red Blood Cells or Erythrocytes Biconcave disk
• Increases surface area:volume ratio• Spectrin flexible protein
Anucleate amitotic
Shape of a RBC
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Hemoglobin: Structure & Fxn
Globin protein consists of 4 polypeptides (22)• 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
Sickle-cell anemia –• Defective HgB gene (HbS)• RBC’s become sickle-shaped
in low oxygen situations• Cause anemia, ischemia &
infarctionhttp://www.nlm.nih.gov/medlineplus/ency/imagepages/1223.htm
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Red blood celldeath andphagocytosis
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
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Globin
Red blood celldeath andphagocytosis
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
Heme2
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Aminoacids
Reused forprotein synthesisGlobin
Red blood celldeath andphagocytosis
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
Heme
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
Heme
4
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Liver
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
FerritinHeme
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3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
FerritinHeme
654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Macrophage inspleen, liver, orred bone marrow
FerritinHeme Fe3+
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654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Circulation for about120 days
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Macrophage inspleen, liver, orred bone marrow
FerritinHeme Fe3+
8
7
654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Circulation for about120 days
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Macrophage inspleen, liver, orred bone marrow
FerritinHeme
Biliverdin Bilirubin
Fe3+
9
8
7
654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Circulation for about120 days
Bilirubin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Macrophage inspleen, liver, orred bone marrow
FerritinHeme
Biliverdin Bilirubin
Fe3+
10
9
8
7
654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Stercobilin
Bilirubin
Urobilinogen
Feces
Smallintestine
Circulation for about120 days
Bacteria
Bilirubin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Macrophage inspleen, liver, orred bone marrow
FerritinHeme
Biliverdin Bilirubin
Fe3+
12
1110
9
8
7
654
3
2
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Aminoacids
Reused forprotein synthesisGlobin
Urine
Stercobilin
Bilirubin
Urobilinogen
Feces
Smallintestine
Circulation for about120 days
Bacteria
Bilirubin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Kidney
Macrophage inspleen, liver, orred bone marrow
Ferritin
Urobilin
Heme
Biliverdin Bilirubin
Fe3+
13 12
1110
9
8
7
654
3
2
1
Aminoacids
Reused forprotein synthesisGlobin
Urine
Stercobilin
Bilirubin
Urobilinogen
Feces
Largeintestine
Smallintestine
Circulation for about120 days
Bacteria
Bilirubin
Red blood celldeath andphagocytosis
Transferrin
Fe3+
Fe3+ Transferrin
Liver
+Globin
+Vitamin B12
+Erythopoietin
Key:
in blood
in bile
Erythropoiesis inred bone marrow
Kidney
Macrophage inspleen, liver, orred bone marrow
Ferritin
Urobilin
Heme
Biliverdin Bilirubin
Fe3+
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13 12
1110
9
8
7
654
3
2
1
Formation and Destruction of RBC’s: Recycling of HgB
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Formation and Destruction of RBC’s: Recycling of HgB
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Erythropoiesis: Production of RBC
Requires protein, lipids, CHO, iron, vB12, folic acid Three phases in developmental pathway
• Reticulocyte Erythrocyte- Reticulocyte count = Diagnostic test
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Total Erythrocytes (RBC)
Circulating erythrocytes
• # remains constant• Normal RBC count
- male 5.4 million/drop - female 4.8
million/drop
Reticulocytes• Should be ~1% of
circulating RBC’s
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%
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Erythropoietin Mechanism
Reduces O2
levels in blood
Erythropoietin stimulates red bone marrow
Enhanced erythropoiesis increases RBC count
Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2
to blood, or increased tissue demands for O2
Start
Kidney (and liver to a smaller extent) releases erythropoietin
Increases O2-carrying ability of blood
Erythropoietin Mechanism
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Erythrocyte Disorders
Polycythemia• Compensatory – smokers• Relative – dehydration• Erythrocytosis – EPO high• Induced polycythemia
- Blood dopingi. recEPO or injecting previously stored RBC’s before an
athletic event more cells available to deliver oxygen to tissues
ii. Dangerous increases blood viscosity forces heart to work harder banned by Olympic committee
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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
• Sickle-cell anemia
Fig 1. Normal bone marrow. 30-70% of marrow space consists of hematopoeitic cells w/ remainder being fat.
Fig 2. Patient's bone marrow biopsy w/ almost no identifiable hematopoeisis.
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White Blood Cells/ Leukocytes
“Complete” blood cells • Far less numerous than
RBCs
Usually live a few days• Except for lymphocytes
– live for months or years
Leukocytosis Leukopenia
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Leukocyte Functions:
Inflammation & fight infection
• Emigration• Chemotaxis • Diapedesis
- Adhesion molecules (Selectins & integrins)
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Classification of Leukocytes
Granulocytes • neutrophils, eosinophils, basophils,
dendritic cells
Agranulocytes • monocytes (m) 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 circulating WBCs
• Multi-lobed nuclei• Granules = peroxidases,
hydrolytic enz & defensins
• Band (shift)
Functions target bacteria
• 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-Ag complexes
• 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, bilobed
nuclei 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 WBC’s Physical features
• U or kidney shaped nucleus
Migratory• Differentiate into macrophage (m)
- Fixed m- Free (wandering) m
Phagocytes• Antigen presenting cell (APC) via
MHC (major histocompatibility complex)
http://www.physioweb.org/blood_cells.html
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Lymphocyte (Agranulocyte)
General features• ~25% of circulating
WBCs• Dark, oval to round
nucleus
Types of lymphocytes• NK cells (Innate)
- Viral infected & tumor cells
• B cells (plasma)- Make antibody to
antigens• T cells
- virus, fungi, cancer, some bacteria, transplants
http://greenfield.fortunecity.com/rattler/46/blood.htm
http://www.phototakeusa.com/results.asp?txtkeys=Dennis+Kunkel
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Clinical Application: Leukemia
Acute leukemia• uncontrolled
production of immature leukocytes
Chronic leukemia• accumulation of
mature WBC in bloodstream because they 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, ovarian or testicular cancer, lymphoma or aplastic anemia
- 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-Host
Disease• Stem cells taken from
umbilical cord & frozen -painless