Chapter 19

Cardiovascular System: The Blood

Hematology Cells immersed in body fluids:

Blood
Plasma Formed elements (cells)

Interstitial fluid

Functions of Blood

Transportation Regulation

pH body temp H2O content of cells BP

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

Protection

Blood loss Immunity

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Physical Characteristics of Blood

Avg volume Consistency Color Temperature pH ~7.4

http://www.phototakeusa.com/results.asp?txtkeys=Dennis+Kunkel

Blood Sampling Phlebotomy

Venipuncture (most common)

Arterial stick

Blood Sampling Phlebotomy

Finger or heel stick

Capillary sample

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/Lymphocyt

Components of Blood: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

Stages of Hematopoiesis

Pluripotent hematopoietic stem cell Myeloid stem cells

Lymphoid stem cells

Progenitor cells (CFU) Erythroblast reticulocyte RBC Megakaryocyte thrombocyte Granulocytes (PMN, basophil, eosinophil) Monocyte macrophage Dendritic cell T, B & NK cells

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

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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 or faulty globin chain in HgB

Sx Tx

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Clinical Application: Abnormal HgB

Sickle-cell anemia

Defective HgB gene (HbS) RBCs become sickle-shaped in low oxygen situations Cause anemia, ischemia & infarction
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1223.htm

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Formation and Destruction of RBCs: Recycling of HgB

Circulation for about 120 days

3
Amino acids Reused for protein synthesis Fe3+ Fe3+ Transferrin

Globin

4 2 Heme
Transferrin

6
Ferritin Fe3+ + Globin + Vitamin B12 + Erythopoietin

9 1 Red blood cell

death and phagocytosis Kidney Biliverdin Bilirubin

Bilirubin

10
Bilirubin

11

Liver

Small intestine

13
Macrophage in spleen, liver, or red bone marrow Urine Urobilin

8 Erythropoiesis in
red bone marrow

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Urobilinogen Stercobilin Feces

Bacteria

Key:
in blood in bile

Large 14 intestine

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Erythropoiesis: Production of RBC

Requires protein, lipids, CHO, iron, vB12, folic acid 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)

Circulating erythrocytes

# remains constant Normal RBC count

male 5.4 million/drop female 4.8 million/drop
http://www.nlm.nih.gov/medlineplus/ency/imagepages/1491.htm

Reticulocytes

Should be ~1% of circulating RBCs

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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
Start Normal blood oxygen levels Stimulus: Hypoxia due to decreased RBC count, decreased availability of O2 to blood, or increased tissue demands for O2

Increases O2-carrying ability of blood Reduces O2 levels in blood

Enhanced erythropoiesis increases RBC count

Erythropoietin stimulates red bone marrow

Kidney (and liver to a smaller extent) releases erythropoietin

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Erythrocyte Disorders

Polycythemia Blood doping

Induced polycythemia recEPO or injecting previously stored RBCs before an athletic event
more cells available to deliver oxygen to tissues

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:

Fig 1. Normal bone marrow. 30-70% of marrow space consists of hematopoeitic cells w/ remainder being fat.

Hemorrhagic anemia Hemolytic anemia Aplastic anemia

Iron-deficiency anemia
Pernicious anemia
Fig 2. Patient's bone marrow biopsy w/ almost no identifiable hematopoeisis. 22

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 (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 circulating WBCs Multi-lobed nuclei Granules = peroxidases, hydrolytic enz & defensins Band (shift)

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

Functions target bacteria

Lysozymes Defensin proteins Strong oxidants Phagocytosis

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

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Eosinophils (Granulocyte)
http://greenfield.fortunecity.com/rattler/46/blood.htm

~1-4% circulating WBC

Nucleus w/ 2-3 lobes

Large, uniform-sized granules stain orangered w/ acidic dyes

Functions

Release histaminase Phagocytize Ab-Ag complexes Attack parasitic worms

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

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Basophils (Granulocyte)

< 1% of circulating WBC

Large, dark purple, variablesized 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:

RBC Eosinophil

PMN

Basophil
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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

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

Phagocytes

Antigen presenting cell (APC) via MHC (major histocompatibility complex)

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

B cells (plasma)
Make antibody to antigens

T cells
virus, fungi, cancer, some bacteria, transplants

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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

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Platelet (Thrombocyte) Anatomy

Cell fragment (anucleate)

Formed in bone marrow Myeloid stem cell megakaryoblast megakaryocyte 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

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

Purpuric spots
petechiae ecchymoses

Thrombocythemia (Thrombocytosis)
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http://www.healthsystem.virginia.edu/internet/hematology/hessidb/Platelet-Disorders.cf

Hemostasis

Quick stoppage of bleeding in localized area

Prevents hemorrhage

Rapid sequence of events:

1. 2. 3.

Vascular spasm (Vasoconstriction) Platelet plug formation (Primary hemostasis) Coagulation (Secondary hemostasis)

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Red blood cell

Platelet

Platelet Plug Formation

Collagen fibers and damaged endothelium

1 1 Platelet adhesion

Liberated ADP, serotonin, and thromboxane A2 22

Platelet release reaction

Platelet plug

3 3

Platelet aggregation

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(a) Extrinsic pathway

(b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers

Stages of Clotting:

Tissue trauma

Clot = Fibrin + trapped RBC

Tissue factor (TF)

Clotting factors

Damaged platelets

Activated XII

Involves three stages:

1. 2. 3. Formation of prothrombinase Convert prothrombin thrombin Convert fibrinogen fibrin
1

Ca2+

Ca2+

Activated platelets

+
Platelet phospholipids

Activated X Activated X V Ca2+ (c) Common pathway Ca2+ Prothrombin (II) Ca2+ V +

PROTHROMBINASE

Two Pathways:

Contact Activation pathway (formerly Intrinsic Pathway) Tissue Factor pathway (formerly Extrinsic pathway)

THROMBIN
Ca2+
Fibrinogen (I) Loose fibrin threads XIII

Activated XIII

STRENGTHENED FIBRIN THREADS

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Extrinsic Pathway (Tissue Factor Pathway)

Formation of prothrombinase

(a) Extrinsic pathway Tissue trauma

(b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers

Damaged tissue leaks tissue factor (thromboplastin) Add in Ca2+ + Factor V/X Produce prothrombinase
Ca2+

Tissue factor (TF)

Damaged platelets

Activated XII Ca2+ Activated platelets

Platelet phospholipids

Activated X Activated X V V Ca2+ Ca2+

PROTHROMBINASE

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Intrinsic Pathway (Contact Activation)

Activation (endothelium damaged)

(a) Extrinsic pathway Tissue trauma

(b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers

Platelets bind collagen Activated platelets release phospholipids Ca+2 + factors XII activation of factors X & V prothrombinase
1
Ca2+

Tissue factor (TF)

Damaged platelets

Activated XII Ca2+ Activated platelets

Platelet phospholipids

Activated X Activated X V Ca2+ Ca2+ V

PROTHROMBINASE

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(a) Extrinsic pathway

(b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers

Common Pathway

Tissue trauma

Prothrombinase + Ca+2

Tissue factor (TF)

Converts prothrombin thrombin Thrombin + Ca+2 + XIIIa converts fibrinogen to insoluble fibrin

Damaged platelets

Activated XII Ca2+ Ca2+ Activated platelets

+
Platelet phospholipids

Activated X Activated X

Positive feedback mechanism

Ca2+ (c) Common pathway

Ca2+

V +

PROTHROMBINASE

Accelerates formation of prothrombinase Activates platelets to release phospholipids

Ca2+ Prothrombin (II)

THROMBIN

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(a) Extrinsic pathway

(b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers

Blood Clotting

Tissue trauma

Serum

Tissue factor (TF)

Clotting

blood plasma w/o clotting proteins

Ca2+

Damaged platelets

Activated XII Ca2+ Activated platelets

Clotting factors

series of chemical rxns formation of fibrin threads

1

+
Platelet phospholipids

Activated X Activated X V Ca2+ (c) Common pathway Ca2+ Prothrombin (II) Ca2+ V +

PROTHROMBINASE

Ca+2,

inactive enzymes, & various molecules associated w/ platelets or released by damaged tissues

THROMBIN
Ca2+ Fibrinogen (I) Loose fibrin threads XIII

Activated XIII

STRENGTHENED FIBRIN THREADS

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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/ATHHT

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Anticoagulants

Oral anticoagulants antagonize effects of Vit K

Warfarin (Coumadin)

Heparin blocks thrombin formation

In vivo & in vitro

Low dose aspirin (antiprostaglandin)

Blocks synthesis of thromboxane A2 Inhibits vasoconstriction & platelet aggregation 75 or 81mg Baby aspirin
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Thrombolytic agents

Thrombolytic agents

Dissolve clots

Common drugs

tPA tissue plasminogen activator streptokinase

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Clinical Application: Hemophilia

Inherited deficiency of clotting factors

bleeding spontaneously or after minor trauma

Treatment

Transfusions Clotting factors

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Blood Groups and Blood Types

Genetically determined Categorized into blood groups based on presence/ absence of antigens Major blood groups = ABO & Rh groups

Other blood groups include Lewis, Kell, Kidd & Duffy systems

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RH blood groups

Discovered in Rhesus monkey blood Rh+ vs Rh

Normal plasma contains no anti-Rh Ab Transfusion rxn upon 2nd exposure hemolysis of RBCs
http://www.biologymad.com/master.html?http://www.biologymad.com/Immunology/Immunology.htm

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ABO Blood System

Plasma contains isoantibodies (agglutinins) to A, B or Rh Ag not found in your blood Transfusion reactions

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

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Transfusion & Transfusion Reactions

Transfusion Incompatible blood transfusions

Incompatibility between donor & recipient Causes:

Agglutination
i.

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

http://www.nobel.se/medicine/educational/landsteiner/readmore.html

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