Transcript Noise Paper - Damien Rutkoski

Chapter 18
Blood
Overview of blood circulation

•

•
Oxygen (O2) and nutrients diffuse across
capillary walls and enter tissues

•
Carbon dioxide (CO2) and wastes move from
tissues into the blood

•
Oxygen-deficient blood leaves the capillaries
and flows in veins to the heart

•
This blood flows to the lungs where it
releases CO2 and picks up O2

Blood leaves the heart via arteries that branch
repeatedly until they become capillaries
•
The oxygen-rich blood returns to the heart
Composition of Blood

•

•
It is composed of liquid plasma and formed
elements

•
Blood is the body’s only fluid tissue
Formed elements include:
• Erythrocytes, or red blood cells (RBCs)

• Leukocytes, or white blood cells (WBCs)

• Platelets
•
Hematocrit – the percentage of RBCs out of the
total blood volume


Erythrocytes
Leukocytes
Platelets
Physical Characteristics and Volume

•
Blood is a sticky, opaque fluid with a metallic
taste

•
Color varies from scarlet (oxygen-rich) to dark
red (oxygen-poor)

•

•
Temperature is 38C, slightly higher than
“normal” body temperature

•
Blood accounts for approximately 8% of body
weight

•
Average volume of blood is 5–6 L for males,
and 4–5 L for females
The pH of blood is 7.35–7.45
Functions of Blood

•
Blood performs a number of functions dealing
with:



• Substance distribution
• Regulation of blood levels of particular
substances
• Body protection
Distribution

•
Blood transports:



• Oxygen from the lungs and nutrients from
the digestive tract
• Metabolic wastes from cells to the lungs
and kidneys for elimination
• Hormones from endocrine glands to target
organs
Regulation

•
Blood maintains:



• Appropriate body temperature by
absorbing and distributing heat
• Normal pH in body tissues using buffer
systems
• Adequate fluid volume in the circulatory
system
Protection

•
Blood prevents blood loss by:
• Activating plasma proteins and platelets

• Initiating clot formation when a vessel is
broken
Blood prevents infection by:


•



• Synthesizing and utilizing antibodies
• Activating complement proteins
• Activating WBCs to defend the body
against foreign invaders
Blood Plasma

•
Blood plasma contains over 100 solutes,
including:





• Proteins – albumin, globulins, clotting
proteins, and others
• Nonprotein nitrogenous substances – lactic
acid, urea, creatinine
• Organic nutrients – glucose,
carbohydrates, amino acids
• Electrolytes – sodium, potassium, calcium,
chloride, bicarbonate
• Respiratory gases – oxygen and carbon
dioxide
Formed Elements

•
Erythrocytes, leukocytes, and platelets make up
the formed elements
• Only WBCs are complete cells

• RBCs have no nuclei or organelles, and
platelets are just cell fragments
•
Most formed elements survive in the
bloodstream for only a few days



•
Most blood cells do not divide but are renewed
by cells in bone marrow
Erythrocytes(RBC's)

•
Biconcave discs, anucleate, essentially no
organelles

•
Filled with hemoglobin (Hb), a protein that
functions in gas transport

•
Contain the plasma membrane protein spectrin
that:
• Gives erythrocytes their flexibility

• Allows them to change shape as necessary
•
Erythrocytes are an example of the
complementarity of structure and function


Structural characteristics that contribute to its gas transport function
are:



• Biconcave shape that has a huge surface
area to volume ratio
• Discounting water content, erythrocytes
are 97% hemoglobin
• ATP is generated anaerobically, so the
erythrocytes do not consume the oxygen they
transport
Erythrocycte Function
•
Erythrocytes are dedicated to respiratory gas transport

•
Hemoglobin reversibly binds with oxygen and
most oxygen in the blood is bound to hemoglobin

•
Hemoglobin is composed of:



• The protein globin, made up of two alpha
and two beta chains, each bound to a heme
group
• Each heme group bears an atom of iron,
which can bind one to oxygen molecule
•
Each hemoglobin molecule can transport four
molecules of oxygen
Hemoglobin(Hb)
•
Oxyhemoglobin – hemoglobin bound to oxygen
• Oxygen loading takes place in the lungs
•
Deoxyhemoglobin – hemoglobin after oxygen
diffuses into tissues (reduced Hb)



•
Carbaminohemoglobin – hemoglobin bound to
carbon dioxide

• Carbon dioxide loading takes place in the
tissues
Structure of hemoglobin
Production of Blood Cells
•
Hematopoiesis – blood cell formation

•
Hemopoiesis occurs in the red bone marrow of
the:
• Axial skeleton and girdles

• Epiphyses of the humerus and femur
Hemocytoblasts give rise to all formed elements


•
Production of
Erythrocytes:Erythropoiesis
•
A hemocytoblast is transformed into a committed cell called
the proerythroblast

•

•
The developmental pathway consists of three
phases
Proerythroblasts develop into early erythroblasts



• Phase 1 – ribosome synthesis in early
erythroblasts
• Phase 2 – hemoglobin accumulation in late
erythroblasts and normoblasts
• Phase 3 – ejection of the nucleus from
normoblasts and formation of reticulocytes
Reticulocytes then become mature erythrocytes

•
Circulating erythrocytes – the number remains
constant and reflects a balance between RBC
production and destruction
• Too few red blood cells leads to tissue
hypoxia

• Too many red blood cells causes
undesirable blood viscosity
•
Erythropoiesis is hormonally controlled and
depends on adequate supplies of iron, amino acids,
and B vitamins


Hormonal Control of Erythropoiesis
•
Erythropoietin (EPO) release by the kidneys is triggered by:
• Hypoxia due to decreased RBCs

• Decreased oxygen availability

• Increased tissue demand for oxygen
Enhanced erythropoiesis increases the:


•


• RBC count in circulating blood
• Oxygen carrying ability of the blood
increases
Erythropoiesis: Nutrient
Requirements
•
Erythropoiesis requires:
• Proteins, lipids, and carbohydrates

• Iron, vitamin B12, and folic acid
•
The body stores iron in Hb (65%), the liver,
spleen, and bone marrow



•
Intracellular iron is stored in protein-iron
complexes such as ferritin and hemosiderin

•
Circulating iron is loosely bound to the
transport protein transferrin
Fate and Destruction of Erythrocytes
•
The life span of an erythrocyte is 100–120 days

•
Old erythrocytes become rigid and fragile, and
their hemoglobin begins to degenerate

•
Dying erythrocytes are engulfed by
macrophages

•
Heme and globin are separated and the iron is
salvaged for reuse
Fate of Hemoglobin
•
Heme is degraded to a yellow pigment called bilirubin

•
The liver secretes bilirubin into the intestines as
bile

•

•
This degraded pigment leaves the body in feces,
in a pigment called stercobilin

•
Globin is metabolized into amino acids and is
released into the circulation
The intestines metabolize it into urobilinogen
Life Cycle of Red Blood Cells
Erythrocyte Disorders
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•
Anemia – blood has abnormally low oxygencarrying capacity



• It is a symptom rather than a disease itself
• Blood oxygen levels cannot support
normal metabolism
• Signs/symptoms include fatigue, paleness,
shortness of breath, and chills
Anemia: Insufficient Erythrocyctes
•
Hemorrhagic anemia – result of acute or chronic loss of blood

•
Hemolytic anemia – prematurely ruptured
erythrocytes

•
Aplastic anemia – destruction or inhibition of
red bone marrow
Anemia: Decreased Hemoglobin
Content
•
Iron-deficiency anemia results from:
• A secondary result of hemorrhagic anemia

• Inadequate intake of iron-containing foods

• Impaired iron absorption
Pernicious anemia results from:
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•
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•
Deficiency of vitamin B12
Often caused by lack of intrinsic factor
needed for absorption of B12
•
•
Anemia: Abnormal Hemoglobin
Thalassemias – absent or faulty globin chain in hemoglobin
• Erythrocytes are thin, delicate, and
deficient in hemoglobin
•
Sickle-cell anemia – results from a defective
gene coding for an abnormal hemoglobin called
hemoglobin S (HbS)


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
• HbS has a single amino acid substitution
in the beta chain
• This defect causes RBCs to become
sickle-shaped in low oxygen situations
Polycythemia
•
Polycythemia – excess RBCs that increase blood viscosity

•
Three main polycythemias are:
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•
•
•
Polycythemia vera
Secondary polycythemia
Blood doping
Leukocytes(WBCs)
•
Leukocytes, the only blood components that are complete
cells:
• Are less numerous than RBCs

• Make up 1% of the total blood volume

• Can leave capillaries via diapedesis

• Move through tissue spaces
•
Leukocytosis – WBC count over 11,000 per
cubic millimeter



• Normal response to bacterial or viral
invasion
Classification of Leukocytes:
Granulocytes
•
Granulocytes – neutrophils, eosinophils, and basophils




• Contain cytoplasmic granules that stain
specifically (acidic, basic, or both) with
Wright’s stain
• Are larger and usually shorter-lived than
RBCs
• Have lobed nuclei
• Are all phagocytic cells
Neutrophils
•
Neutrophils have two types of granules that:
• Take up both acidic and basic dyes

• Give the cytoplasm a lilac color

• Contain peroxidases, hydrolytic enzymes,
and defensins (antibiotic-like proteins)
Neutrophils are our body’s bacterial slayers


•
Eosinophils
•
Eosinophils account for 1–4% of WBCs




• Have red-staining, bi-lobed nuclei
connected via a broad band of nuclear
material
• Have red to crimson (acidophilic) large,
coarse, lysosome-like granules
• Lead the body’s counterattack against
parasitic worms
• Lessen the severity of allergies by
phagocytizing immune complexes
Basophils
•
Account for 0.5% of WBCs and:


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• Have U or Sshaped nuclei with two or
three conspicuous constrictions
• Are functionally similar to mast cells
• Have large, purplish-black (basophilic)
granules that contain histamine
 • Histamine – inflammatory chemical
that acts as a vasodilator and attracts
other WBCs
Agranulocytes
•
Agranulocytes – lymphocytes and monocytes:



• Lack visible cytoplasmic granules
• Are similar structurally, but are
functionally distinct and unrelated cell types
• Have spherical (lymphocytes) or kidneyshaped (monocytes) nuclei
Lymphocytes
•
Have large, dark-purple, circular nuclei with a thin rim of
blue cytoplasm

•
Found mostly enmeshed in lymphoid tissue
(some circulate in the blood)

•
There are two types of lymphocytes: T cells and
B cells

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• T cells function in the immune response
• B cells give rise to plasma cells, which
produce antibodies
Neutrophils contains
fine granules
a 3-6 lobed nucleus
Eosinophils large
course granules
bi-lobed nucleus
Basophils stains
very dark
large histamine
granules
Monocytes
•
Monocytes account for 4–8% of leukocytes
• They are the largest leukocytes

• They have abundant pale-blue cytoplasms

• They have purple staining, U- or kidneyshaped nuclei

• They leave the circulation, enter tissue,
and differentiate into macrophages
Macrophages:

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•

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• Are highly mobile and actively phagocytic
• Activate lymphocytes to mount an
immune response
3). Platelets
Production of Leukocytes
•
Leukopoiesis is hormonally stimulated by two families of
cytokines (hematopoetic factors) – interleukins and colonystimulating factors (CSFs)
• Interleukins are numbered (e.g., IL-1, IL2), 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

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•
Many hematopoietic hormones are used
clinically to stimulate bone marrow
•
Formation of Leukocytes
All leukocytes originate from hemocytoblasts

•
Hemocytoblasts differentiate into myeloid stem
cells and lymphoid stem cells

•
Myeloid stem cells become myeloblasts or
monoblasts
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•

•
Myeloblasts develop into eosinophils,
neutrophils, and basophils

•
Monoblasts develop into monocytes

•
Lymphoblasts develop into lymphocytes
Lymphoid stem cells become lymphoblasts
Leukocyte Disorders: Leukemias
•
Leukemia refer to cancerous conditions involving white
blood cells

•
Leukemias are named according to the abnormal
white blood cells involved
• Myelocytic leukemia – involves
myeloblasts

• Lymphocytic leukemia – involves
lymphocytes
•
Acute leukemia involves blast-type cells and
primarily affects children


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•
Chronic leukemia is more prevalent in older
people
Myelocytic leukemia
Leukemia
•
Immature white blood cells are found in the bloodstream in all
leukemias

•
Bone marrow becomes totally occupied with
cancerous leukocytes

•
The white blood cells produced, though
numerous, are not functional

•
Death is caused by internal hemorrhage and
overwhelming infections

•
Treatments include irradiation, antileukemic
drugs, and bone marrow transplants
Platelets
•
Platelets are fragments of megakaryocytes with a bluestaining outer region and a purple granular center

•
The granules contain serotonin, Ca2+, enzymes,
ADP, and platelet-derived growth factor (PDGF)

•
Platelets function in the clotting mechanism by
forming a temporary plug that helps seal breaks in
blood vessels
Genesis of Platelets
•
The stem cell for platelets is the hemocytoblast

•
The sequential developmental pathway is
hemocytoblast, megakaryoblast, promegakaryocyte,
megakaryocyte, and platelets
Hemostasis
•
A series of reactions designed for stoppage of bleeding

•
During hemostasis, three phases occur in rapid
sequence

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
• Vascular spasms – immediate
vasoconstriction in response to injury
• Platelet plug formation
• Coagulation (blood clotting)
Platelet Plug Formation
•
Platelets do not stick to each other or to the endothelial lining
of blood vessels

•
Upon damage to a blood vessel, platelets:
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 PGI2

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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
Coagulation
•
The final thee 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
Detailed Reactions of Hemostatis
Coagulation Phase 1: Two Pathways to Prothrombin Activator

•
May be initiated by either the intrinsic or
extrinsic pathway
• Triggered by tissue-damaging events

• Involves a series of procoagulants

• Each pathway cascades toward factor X
•
Once factor X has been activated, it complexes
with calcium ions, PF3, and factor V to form
prothrombin activator



Coagulation Phase 2: Pathway to Thrombin

•
Prothrombin activator catalyzes the
transformation of prothrombin to the active the
enzyme thrombin

Coagulation Phase 3: Common Pathways to the Fibrin Mesh

•
Thrombin catalyzes the polymerization of
fibrinogen into fibrin

•
Insoluble fibrin strands form the structural basis
of a clot
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•
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•
Fibrin in the presence of calcium ions activates
factor XIII that:
Fibrin causes plasma to become a gel-like trap

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•
•
Cross-links fibrin
Strengthens and stabilizes the clot
Clot Retraction and Repair
•
Clot retraction – stabilization of the clot by squeezing serum
from the fibrin strands

•
Repair



• Platelet-derived growth factor (PDGF)
stimulates rebuilding of blood vessel wall
• Fibroblasts form a connective tissue patch
• Endothelial cells multiply and restore the
endothelial lining
Factors Limiting Clot Growth or
Formation
•
Two homeostatic mechanisms prevent clots from becoming
large

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•
•
Swift removal of clotting factors
Inhibition of activated clotting factors
Inhibition of Clotting Factors
•
Fibrin acts as an anticoagulant by binding thrombin and
preventing its:
• Positive feedback effects of coagulation

• Ability to speed up the production of
prothrombin activator via factor V

• Acceleration of the intrinsic pathway by
activating platelets
•
Thrombin not absorbed to fibrin is inactivated
by antithrombin III


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•
Heparin, another anticoagulant, also inhibits
thrombin activity
Factors Preventing Undersirable
Clotting
•
Unnecessary clotting is prevented by the structural and
molecular characteristics of endothelial cells lining the blood
vessels

•
Platelet adhesion is prevented by:



• The smooth endothelial lining of blood
vessels
• Heparin and PGI2 secreted by endothelial
cells
• Vitamin E quinone, a potent anticoagulant
Hemostasis Disorders:
Thromboembolytic Disorders
•
Thrombus – a clot that develops and persist in an unbroken
blood vessel
• Thrombi can block circulation, resulting in
tissue death

• Coronary thrombosis – thrombus in blood
vessel of the heart
•
Embolus – a thrombus freely floating in the
blood stream


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• Pulmonary emboli can impair the ability
of the body to obtain oxygen
• Cerebral emboli can cause strokes
Prevention of Undesirable Clots
•
Substances used to prevent undesirable clots include:




• Aspirin – an antiprostaglandin that inhibits
thromboxane A2
• Heparin – an anticoagulant used clinically
for pre- and postoperative cardiac care
• Warfarinin – used for those prone to atrial
fibrillation
• Flavonoids – substances found in tea, red
wine, and grape juice that have natural
anticoagulant activity
Hemostasis Disorders: Bleeding
Disorders
•
Thrombocytopenia – condition where the number of
circulating platelets is deficient




• Patients show petechiae (small purple
blotches on the skin) due to spontaneous,
widespread hemorrhage
• Caused by suppression or destruction of
bone marrow (e.g., malignancy, radiation)
• Platelet counts less than 50,000/mm3 is
diagnostic for this condition
• Treated with whole blood transfusions
Hemostatis Disorders: Bleeding
Disorders
•
Inability to synthesize procoagulants by the liver results in
severe bleeding disorders

•
Causes can range from vitamin K deficiency to
hepatitis and cirrhosis

•
Inability to absorb fat can lead to vitamin K
deficiencies as it is a fat-soluble substance and is
absorbed along with fat

•
Liver disease can also prevent the liver from
producing bile, which is required for fat and vitamin
K absorption
Hemophilias – hereditary bleeding disorders caused by lack of
clotting factors
• Hemophilia A – most common type (83%
of all cases) due to a deficiency of factor VIII

• Hemophilia B – results from a deficiency
of factor IX

• Hemophilia C – mild type, caused by a
deficiency of factor XI
•
Symptoms include prolonged bleeding and
painful and disabled joints



•
Treatment is with blood transfusions and the
injection of missing factors
Blood Transfusions
•
Transfusions are necessary:
• When substantial blood loss occurs

• In certain hemostatis disorders
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


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/absence of these antigens are used to classify blood
groups

•

•
The antigens of the ABO and Rh blood groups cause vigorous
transfusion reactions when they are improperly transfused

•
Other blood groups (M, N, Dufy, Kell, and Lewis) are mainly
used for legalities
Humans have 30 varieties of naturally occurring RBC antigens
ABO Blood Groups
•
The ABO blood groups consists of:
• Two antigens (A and B) on the surface of
the RBCs

• Two antibodies in the plasma (anti-A and
anti-B)
•
An individual with ABO blood may have
various types of antigens and spontaneously
preformed antibodies



•
Agglutinogens and their corresponding
antibodies cannot be mixed without serious
hemolytic reactions
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 expose to Rh+ blood will result in a
typical transfusion reaction
Hemolytic Disease of the Newborn
•
Hemolytic disease of the newborn – Rh+ antibodies of a sensitized
Rh– mother cross the placenta and attack and destroy the RBCs of an Rh+
baby

•
Rh– mother become sensitized when Rh+ blood (from
a previous pregnancy of an Rh+ baby or a Rh+ transfusion)
causes her body to synthesis Rh+ antibodies

•
The drug RhoGAM can prevent the Rh– mother from
becoming sensitized

•
Treatment of hemolytic disease of the newborn
involves pre-birth transfusions and exchange transfusions
after birth
Transfusions Reactions
•
Transfusion reactions occur when mismatched blood is
infused

•
Donor’s cells are attacked by the recipient’s
plasma agglutinins causing:
• Diminished oxygen-carrying capacity

• Clumped cells that impede blood flow

• Ruptured RBCs that release free
hemoglobin into the bloodstream
•
Circulating hemoglobin precipitates in the
kidneys and causes renal failure


Blood Typing
•
When serum containing anti-A or anti-B agglutinins is added
to blood, agglutination will occur between the agglutinin and the
corresponding agglutinogens

•
Positive reactions indicate agglutination
Percentage of Population with each Blood Types
Rh+
Rh-
O
38.5%
6.5%
A
34.3%
5.7%
B
8.6%
1.4%
AB
4.3%
0.7%
Plasma Volume Expanders
•
When shock is imminent from low blood volume, volume
must be replaced

•
Plasma or plasma expanders can be
administered

•
Plasma expanders:
• Have osmotic properties that directly
increase fluid volume

• Are used when plasma is not available

• Examples: purified human serum albumin,
plasminate and dextran
•
Isotonic saline can also be used to replace lost
blood volume


Diagnostic Blood Tests

Diagnostic Blood Tests

•
Laboratory examination of blood can assess an
individual’s state of health

•
Microscopic examination:
• Variations in size and shape of RBCs –
predictions of anemias

• Type and number of WBCs – diagnostic of
various diseases
•
Chemical analysis can provide a comprehensive
picture of one’s general health status in relation to
normal values


Developmental Aspects
•
Before birth, blood cell formation takes place in the fetal
yolk sac, liver, and spleen

•
By the 7th month, red bone marrow is the
primary hematopoietic area

•
Blood cells develop from mesenchymal cells
called blood islands

•
The fetus forms HbF, which has a higher affinity
for oxygen than adult hemoglobin
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