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Blood

The only fluid tissue

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Figure 17.10

Blood Composition

Blood: a fluid connective tissue composed of

Plasma

Formed elements

Erythrocytes (red blood cells, or RBCs)

Leukocytes (white blood cells, or WBCs)

Platelets

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Blood Composition

Hematocrit

Percent of blood volume that is RBCs

47% 5% for males

42% 5% for females

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Components of Whole Blood

Plasma expanders restore blood volume, not O2


Packed cells restore O2, maybe not volume
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Figure 17.1

Physical Characteristics and Volume

Blood is a sticky, opaque fluid with a metallic taste

Color varies from scarlet (> O2) to dark red (<O2)

The pH of blood is 7.357.45

Temperature is 38C

Blood accounts for approximately 8% of body


weight

Average volume: 56 L for males, and 45 L for


females

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Functions of Blood

Delivers Oxygen to tissues- from lungs

Picks up Carbon dioxide from the tissues- to


lungs

Distribution

Regulation

Protection

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Functions of Blood
1. Distribution of :

O2 and nutrients to body cells

Metabolic wastes to the lungs and kidneys for


elimination

Hormones from endocrine organs to target organs

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Functions of Blood
Regulation of

2.

Body temperature by absorbing and distributing


heat

Normal pH using buffers

Adequate fluid volume in the circulatory system

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Protection

Hemostasis

Activating plasma proteins & platelets

Clot formation when a vessel is broken

Immune functions

Antibodies- B cells

Activating complement proteins

Activating WBCs to defend the body against


foreign invaders - Tcells

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Blood Plasma

Nitrogenous by-products of metabolismlactic


acid, urea, creatinine

Nutrientsglucose, carbohydrates, amino acids

ElectrolytesNa+, K+, Ca2+, Cl, HCO3

Respiratory gasesO2 and CO2

Hormones

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Blood Plasma

90% water

Proteins are mostly produced by the liver

60% albumin

36% globulins

4% fibrinogen

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Formed Elements

Erythrocytes, leukocytes, and platelets make up the


formed elements

WBCs - cells

RBCs - no nuclei, few organelles; a sack of hgb

platelets - cell fragments; thrombocytes

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Megakaryocyte

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Components of Whole Blood

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Figure 17.2

Erythrocytes (RBCs)

No nucleus

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Figure 17.3

Erythrocytes

Structural characteristics contribute to gas transport

Biconcave shapehuge surface area relative to


volume

> 97% hemoglobin (not counting water)

No mitochondria; ATP production is anaerobic; no


O2 is used in generation of ATP

A superb example of complementarity of structure


and function!

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Structure of Hemoglobin

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Figure 17.4

Hemoglobin (Hb)

Oxyhemoglobin oxygen bound to Hgb (or Hb)

Deoxyhemoglobin - oxygen dissociates from hgb


& diffuses into tissues (reduced Hgb)

Carbaminohemoglobin carbon dioxide bound


Hgb

PLAY

InterActive Physiology :
Respiratory System: Gas Transport, pages 313

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Erythrocyte Function

RBCs are dedicated to respiratory gas transport

Hemoglobin binds reversibly with oxygen

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Hematopoiesis

Hematopoiesis

Red bone marrow of the:

Axial skeleton (sternum) and girdles (iliac crest)

Epiphyses of the humerus and femur

Hemocytoblasts give rise to all formed elements

Pluripotent cell or stem cell

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Production of Erythrocytes: Erythropoiesis


Peripheral Circulation

Bone marrow

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Figure 17.5

Regulation of Erythropoiesis

Normal RBC: 4.2-6.1 x 106/ ul whole blood

< RBCs = tissue hypoxia

> RBCs = > blood viscosity

Erythropoietin (kidneys) stimulates RBC production


RBC production Requires:

iron

amino acids

B vitamins

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Erythropoietin Mechanism
Im b
ala
n

ce

Start
Homeostasis: Normal blood oxygen levels
Im b
ala
n

ce

Stimulus: Hypoxia due to


decreased RBC count,
decreased amount of
hemoglobin, or decreased
availability of O2

Increases
O2-carrying
ability of blood

Reduces O2 levels
in blood

Enhanced
erythropoiesis
increases
RBC count

Erythropoietin
stimulates red
bone marrow

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Kidney (and liver to a smaller


extent) releases erythropoietin

Figure 17.6

1 Low O2 levels in blood stimulate


kidneys to produce erythropoietin.
2 Erythropoietin levels
rise in blood.

RBC life cycle(recycle 80-120 days)

3 Erythropoietin and necessary


raw materials in blood promote
erythropoiesis in red bone marrow.
4 New erythrocytes
enter bloodstream;
function about
120 days.

5 Aged and damaged red


blood cells are engulfed by
macrophages of liver, spleen,
and bone marrow; the hemoglobin
is broken down.
Hemoglobin

Heme

Globin

Bilirubin
Amino
acids

Iron stored
as ferritin,
hemosiderin

Iron is bound to
transferrin and released
to blood from liver
as needed for
erythropoiesis
Bilirubin is picked up from
blood by liver, secreted into
intestine in bile, metabolized
to stercobilin by bacteria
and excreted in feces

Circulation

Food nutrients,
including amino
acids, Fe, B12,
and folic acid
are absorbed
from intestine
and enter blood

6 Raw materials are


made available in
blood for erythrocyte
synthesis.

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Figure 17.7

Erythrocyte Disorders Types of Anemia

Anemias - < RBC (normocytic)

Hemorrhagic anemia

Hemolytic anemia

Aplastic anemia

Signs/symptoms include fatigue, paleness,


shortness of breath, and chills

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Types of Anemia : Decreased Hemoglobin Content

Iron-deficiency anemia : (microcytic)

(from hemorrhagic anemia)

< dietary iron

Impaired iron absorption

Pernicious anemia : (macrocytic)

Deficiency of vitamin B12

Lack of intrinsic factor needed for absorption of B12

Treatment is intramuscular injection of B12;


application of Nascobal

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Types of Anemia: Abnormal Hemoglobin

Thalassemias

defective globin chain gene(s)

Many forms

Mediterranean decent

Sickle-cell anemia

defective globin chain gene with a single aa


substitution

This defect causes RBCs to become sickle-shaped


in < oxygen & > oxygen demand situations

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(a) Normal erythrocyte has normal


hemoglobin amino acid sequence
in the beta chain.

146

(b) Sickled erythrocyte results from


a single amino acid change in the
beta chain of hemoglobin.

146

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Figure 17.8

Polycythemia

Polycythemia excess RBCs that increase blood


viscosity

Three main polycythemias are:

Polycythemia vera

Secondary polycythemia test pilots

Blood doping atheletes

RX: phlebotomies

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Leukocytes (WBCs)

Normal WBC: 5-10,000/ ul whole blood

< WBC - leukopenia

from bone marrow suppression

leads to infection

never normal

> WBC leukocytosis; > 11,000/ul

From: infection, exercise, stress, leukemia

Diapedesis- leaks from blood into tissues

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Percentages of Leukocytes

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Figure 17.9

Granulocytes

All have granules, segmented nuclei, and are


phagocytic

Neutrophils segs; first ones to site of


inflammation

Eosinophils

Basophils

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(a) Neutrophil;
multilobed
nucleus

(b) Eosinophil;
bilobed nucleus,
red cytoplasmic
granules

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(c) Basophil;
bilobed nucleus,
purplish-black
cytoplasmic
granules

Figure 17.10 (a-c)

Neutrophils

50-70% total WBC

> Neutrophils bacterial infections

Very active in inflammation

diapedesis

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Eosinophils

14% of WBCs

Red-orange granules (acidophilic)

> : allergies, parasitic infections

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Basophils

0.5% of WBCs

purplish-black (basophilic) granules;

Histamine

Called mast cells in tissues

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(d) Small
lymphocyte;
large spherical
nucleus

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(e) Monocyte;
kidney-shaped
nucleus

Figure 17.10d, e

Lymphocytes

25-45% WBCs

> in viral infections

Large, dark-purple, circular nuclei with a thin rim


of blue cytoplasm

Are found mostly enmeshed in lymphoid tissue


(some circulate in the blood)

T cells and B cells

T cells function in cell mediated immune response

B cells produce antibodies in humoral immune


response

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Monocytes

48% WBC

largest leukocytes

Macrophages in tissue

Phagocytosis, antigen processing or presentation,


inflammation

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Leukocytes

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Figure 17.10

Production of Leukocytes

Leukopoiesis- interleukins & (CSFs)

Interleukins are numbered (e.g., IL-1, IL-2),


whereas CSFs are named for the WBCs they
stimulate (e.g., granulocyte-CSF stimulates
granulocytes)

Macrophages and T cells are the most important


sources of cytokines cytotoxic factors

Many hematopoietic hormones are used clinically


to stimulate bone marrow

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Stem cells

Hemocytoblast

Myeloid stem cell

Committed
Myeloblast
cells

Myeloblast

Lymphoid stem cell

Myeloblast

DevelopPromyelocyte Promyelocyte Promyelocyte


mental
pathway

Eosinophilic
myelocyte

Basophilic
myelocyte

Neutrophilic
myelocyte

Eosinophilic
band cells

Basophilic
band cells

Neutrophilic
band cells

Eosinophils
Basophils Neutrophils
(a)
(b)
(c)

Lymphoblast

Promonocyte

Prolymphocyte

Monocytes

Lymphocytes
(e)

(d)

Agranular leukocytes
Granular leukocytes

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Some become
Macrophages (tissues)

Some
become

Plasma cells

Figure 17.11

Leukocytes Disorders: Leukemias

Leukemias- WBC cancers

Myelocytic leukemia myeloblasts

Lymphocytic leukemia lymphocytes

Acute leukemia- blast-type cells; children

Chronic leukemia more mature cells; adults

Childhood leukemia has high cure rate

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Megakaryocyte

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Genesis of Platelets

The stem cell for platelets is the hemocytoblast

The sequential developmental pathway is as


shown.
Bone marrow
Stem cell

Hemocytoblast

Developmental pathway

Megakaryoblast

Promegakaryocyte

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Megakaryocyte

Platelets

Figure 17.12

Hemostasis

blood stop 3 Phases Involved

1. Vascular spasms immediate vasoconstriction in


response to injury
2. Platelet plug formation
3. Coagulation cascade of rxns ending in fibrin
clot

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Platelet Plug Formation

Platelets do not stick to each other or to blood vessels

Upon damage to blood vessel endothelium platelets:

With the help of von Willebrand factor (VWF) adhere to


collagen

Are stimulated by thromboxane A2

Stick to exposed collagen fibers and form a platelet plug

Release serotonin and ADP, which attract still more


platelets

The platelet plug is limited to the immediate area of injury


by prostacyclin

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Coagulation

A set of reactions in which blood is transformed from a


liquid to a gel

Coagulation follows intrinsic and extrinsic pathways

The final three steps of this series of reactions are:

Prothrombin activator is formed

Prothrombin is converted into thrombin

Thrombin catalyzes the joining of fibrinogen


into a fibrin mesh

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Coagulation

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Figure 17.13a

Detailed Events of Coagulation

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Figure 17.13b

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Figure 17.15

Clot Retraction and Repair

Clot retracts within 30-60

Proteins in platelets squeeze serum from clot

Repair

Platelet-derived growth factor (PDGF) repairs


vessel wall

Fibroblasts form a connective tissue patch

Stimulated by vascular endothelial growth factor


(VEGF), endothelial cells multiply and restore the
endothelial lining

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Fibrinolysis & Control of Clot Formation


As soon as clot is formed, a fibrinolytic process
begins to:
1. inhibit growth of clot
2. to break down the clot (within 2 days)

tPA- tissue plasminogen activator = clot buster

Two mechanisms prevent clot growth

Swift removal of clotting factors

Inhibition of activated clotting factors


Hemostasis vs Fibrinolysis

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Factors Preventing Undesirable Clotting

Unnecessary clotting is prevented by endothelial


lining the blood vessels

Platelet adhesion is prevented by:

The smooth endothelial lining of blood vessels- no


plaques, rough spots

Heparin and PGI2 secreted by endothelial cells

Vitamin E quinone, a potent anticoagulant

INFLAMMATION may lead to > clots

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Hemostasis Disorders:
Thromboembolytic Conditions

Thrombus a clot that develops and persists in an


unbroken blood vessel

Thrombi can block circulation, resulting in tissue


death

Coronary thrombosis thrombus in blood vessel of


the heart

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Hemostasis Disorders:
Thromboembolytic Conditions

Embolus a clot on the move (in blood)

Can be fat, cancer cells, etc.

Thromboembolus- blood clot on the move

Pulmonary emboli can impair the ability of the


body to obtain oxygen

Cerebral emboli can cause strokes

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Prevention of Undesirable Clots

Substances used to prevent undesirable clots:

Aspirin inhibits prostaglandin - thromboxane A2

Heparin an anticoagulant used clinically for preand postoperative cardiac care

Warfarin used for those prone to atrial fibrillation

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Hemostasis Disorders

Disseminated Intravascular Coagulation (DIC): widespread


clotting in intact blood vessels

Poor prognosis

Residual blood cannot clot- thrombin tied up in clot

Blockage of blood flow and severe bleeding follows

Most common in:

Septic shock

A complication of pregnancy

Incompatible blood transfusions

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Hemostasis Disorders: Bleeding Disorders

Thrombocytopenia platelets < 50,000/ul

Petechiae

Caused by suppression or destruction of bone


marrow (e.g., malignancy, radiation)

Treated with whole blood transfusions, plasma


exchanges

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Hemostasis Disorders: Bleeding Disorders

Liver disease

Cant make procoagulants

Cant make vitamin K

Gene defects in genes for clotting factors:

Hemophilia A - factor VIII

Hemophilia B factor IX

Hemophilia C factor XI (mild)

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Blood Transfusions

Whole blood transfusions are used:

When blood loss is substantial

In treating thrombocytopenia

Packed red cells (cells with plasma removed) are


used to treat anemia

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Human Blood Groups

RBC membranes have glycoprotein antigens on


their external surfaces

These antigens are:

Unique to the individual

Recognized as foreign if transfused into another


individual

Promoters of agglutination and are referred to as


agglutinogens

Presence or absence of these antigens is used to


classify blood groups

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Blood Groups

Humans have 30 varieties of naturally occurring


RBC antigens

ABO and Rh antigens are Landsteiner group

Other blood groups (M, N, Dufy, Kell, and Lewis)

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ABO Blood Groups

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Table 17.4

Rh Blood Groups

There are eight different Rh agglutinogens, three of


which (C, D, and E) are common

Presence of the Rh agglutinogens on RBCs is


indicated as Rh+

Anti-Rh antibodies are not spontaneously formed


in Rh individuals

However, if an Rh individual receives Rh+ blood,


anti-Rh antibodies form

A second exposure to Rh+ blood will result in a


typical transfusion reaction

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Hemolytic Disease of the Newborn

Erythroblastosis fetalis or HDN: Rh+ antibodies


of a sensitized Rh mother cross the placenta and
attack and destroy the RBCs of an Rh+ baby

Usually first birth ok

RhoGAM blocks antibodies against Rh+ fetus

RX- pre-birth transfusions; exchange transfusions


after birth

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Transfusion Reactions

Life threatening- mismatched blood is infused

Antigens (cells) & antibodies (plasma) agglutinate:

Diminished oxygen-carrying capacity

Clumped cells that impede blood flow

Ruptured RBCs- release hgb

Hgb ppts in kidneys- renal failure

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Blood Typing
Unknown cells
Blood type being tested

Known antisera
RBC agglutinogens

Serum Reaction
Anti-A

Anti-B

AB

A and B

None

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Blood being tested

Anti-A

Type AB (contains
agglutinogens A and B;
agglutinates with both
sera)

Serum

Anti-B

RBCs

Type A (contains
agglutinogen A;
agglutinates with anti-A)
Type B (contains
agglutinogen B;
agglutinates with anti-B)
Type O (contains no
agglutinogens; does not
agglutinate with either
serum)
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Figure 17.16

Restoring Fluid Volume

Hypovolemic shock

Restore fluid volume-Plasma, plasma expanders

Dextran, plasminate, human serum albumin

OR the following may be better

Normal saline

Electrolyte solution Ringers

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Diagnostic Blood Tests

CBC

# RBCs, WBCs, Hgb, Hct, MCV, MCHC

Differential

Microscopic examination reveals variations in


size and shape of RBCs, indications of anemias

Hct

Serum chemistry analysis can provide a


comprehensive picture of ones general health
status in relation to normal values; i.e. blood
glucose

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Diagnostic Blood Tests

Differential WBC count

Prothrombin time and platelet counts assess


hemostasis

SMAC, a blood chemistry profile

Complete blood count (CBC)

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Developmental Aspects- Hematopoiesis

Fetal blood cells formed in yolk sac, liver, spleen

By 7th month- in red bone marrow

Fetus HbF; > affinity for oxygen than adult


hemoglobin

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Developmental Aspects

Age-related blood problems result from disorders


of the heart, blood vessels, and the immune system

Increased leukemias are thought to be due to the


waning deficiency of the immune system

Abnormal thrombus and embolus formation


reflects the progress of atherosclerosis

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