Transcript Red blood cells

I. Composition of Blood and RBCs
Learning Goals
*1- Describe the components and characteristics
of whole blood
*2- Identify the average blood volume in adults and
describe methods for determining this value
*3-Describe the normal appearance, size, shape,
and number of RBCs or erthrocytes in circulating
blood
4- Describe the structure and function of
hemoglobin
5- Describe the process of red blood cell formation
(erythropoiesis) and destruction
Body Fluids and Functions
3 major body fluids
• 1- interstitial
• 2- intracellular
• 3- blood
Major function of blood
1- pick up and deliver of food, oxygen,
wastes, etc.
2- body’s major heat regulating mechanism
Components of Whole Blood
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
1 Withdraw blood
and place in tube
2 Centrifuge
Erythrocytes
(45% of whole blood)
Formed
elements
Blood Components
• Plasma =fluid portion of the blood
(55%)
• Cells (45%)
– Erythrocytes are red blood cells.
They are responsible for oxygen
distribution.
– Leukocytes are the white blood
cells; they are responsible for
“cleaning” the system of foreign
invaders.
– Thrombocytes or platelets are
responsible for blood clotting
• Serum is the liquid that separates
from the blood when a clot is
formed.
Lymphocyte 1000X
platelet
red blood cells
lymphocyte
nucleus occupies most of small cell
Physical Characteristics & Volume
• Blood is a sticky, opaque fluid with a metallic taste
• Color varies from scarlet (oxygen-rich) to dark red
(oxygen-poor)
• The pH of blood is 7.35–7.45
• Temperature is 38C, slightly higher than “normal”
body temperature
• Blood accounts for approximately 8% of body wt.
• Average volume of blood is 5–6 L for males, and
4–5 L for females
Blood Volume Determination
• 1- Direct method- complete removal of all
blood (experimental animals only)
• 2- Indirect method- “tagging”- analyze a
concentration of blood taken
*less fat = more blood volume
Erythrocytes (RBCs)
Complementarity of structure and
function
•Structural characteristics contribute to
its gas transport function
-Biconcave shape that has a huge
surface area relative to volume
•Discounting water content,
erythrocytes are more than 97%
hemoglobin
•ATP is generated anaerobically, so
the erythrocytes do not consume
the oxygen they transport
Erythrocytes (RBCs)
• Biconcave discs, anucleate, essentially no
organelles
• Filled with hemoglobin (Hb), a protein that
functions in gas transport
• Contain the plasma membrane protein
spectrin and other proteins that:
– Give erythrocytes their flexibility
– Allow them to change shape as necessary
Human Blood
• Red blood cells are most
numerous; 5 to 6 million
per mm3
• White blood cells are
larger and less numerous;
5 to 10,000 per mm3
• Platelets are tiny, cellular
fragments; 350 to 500,00
per mm3
Erythrocyte Function
• Dedicated to respiratory gas transport
• Hemoglobin reversibly binds with oxygen
• 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 to one oxygen molecule
• Each hemoglobin molecule can transport
four molecules of oxygen
Structure of Hemoglobin
Figure 17.4
Hemoglobin
• 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
InterActive Physiology®:
Respiratory System: Gas Transport
PLAY
Production of Erythrocytes
• Hematopoiesis – blood cell formation
• Hematopoiesis occurs in red bone marrow of:
– Axial skeleton and girdles
– Epiphyses of the humerus and femur
• Hemocytoblasts to all formed elements
Erythropoiesis
• Hemocytoblast is transformed into a committed
cell= proerythroblast
• Proerythroblasts develop into early erythroblasts
• The developmental pathway consists of three
phases
– 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
Production of Erythrocytes
Regulation & Requirements for Erythropoiesis
• Circulating erythrocytes – # remains
constant and reflects a balance between
RBC production and destruction
– Too few red blood cells leads to tissue hypoxia
– Too many RBCs undesirable blood viscosity
• Erythropoiesis is hormonally controlled
and depends on adequate supplies of iron,
amino acids, and B vitamins
Fate and Destruction of RBC’s
• Life span of a RBC = 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 and Destruction of RBCs
•
•
•
•
Heme degraded to a yellow pigment= bilirubin
Liver secretes bilirubin into intestines as bile
Intestines metabolize it into urobilinogen
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
• Hb released into the blood is captured by
haptoglobin and phagocytized
Life Cycle
of Red
Blood
Cells
II. White Blood Cells and Platelets
Learning Goals
1-Compare and contrast the structure and
function between each of the
granulocytes and agranulocytes
2-Discuss the stages of development of
leukocytes
3-Discuss the structure, function, and
formation of platelets
Granulocytes
• Granulocytes – neutrophils, eosinophils,
and basophils
– Contain cytoplasmic granules that stain
specifically (acidic, basic, or both) with
Wright’s stain
– Larger and usually shorter-lived than RBCs
– Have lobed nuclei
– Phagocytic cells
Neutrophils
• Neutrophils-two types of granules:
– 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 bacteria
slayers
Neutrophil 1000X
bead-shaped nucleus
red
blood
cells
Eosinophils
• Eosinophils account for 1–4% of WBCs
– Have red-staining, bilobed 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
Eosinophil 1000X
reddish cytoplasm
Basophils
• Account for 0.5% of WBCs:
– U- or S-shaped nuclei with
two or three conspicuous
constrictions
– Functionally ~mast cells
– Large, purplish-black
(basophilic) granules that
contain histamine
• Histamine – inflammatory
chemical that acts as a
vasodilator and attracts
other WBCs
• (antihistamines counter this
effect)
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
• 25% or more of WBCs
• Large, dark-purple, circular nuclei with a
thin rim of blue cytoplasm
– Found mostly enmeshed in lymphoid tissue
(some circulate in the blood)
• Two types: T cells and B cells
– T cells function in the immune response
– B cells  plasma cells, produce antibodies
Monocytes
• 4–8% of Leukocytes
– Largest leukocytes
– Abundant pale-blue cytoplasms
– Purple-staining, U- or kidney-shaped nuclei
– Leave the circulation, enter tissue, and
differentiate into macrophages
Monocytes
Macrophages:
– Highly mobile and actively phagocytic
– Activate lymphocytes immune response
Monocyte 1000X
kidney-shaped nucleus (side view)
platelet
Leukocytes (WBCs)
• Only blood components that are complete cells:
– 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
Production of Leukocytes
• Leukopoiesis is hormonally stimulated by
two families of cytokines (hematopoietic
factors) – interleukins and colonystimulating factors (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
• Many hematopoietic hormones are used
clinically to stimulate bone marrow
Formation of Leukocytes
• Leukocytes originate from hemocytoblasts
• Hemocytoblasts differentiate into myeloid
stem cells and lymphoid stem cells
• Myeloid stem cells become myeloblasts or
monoblasts
• Lymphoid stem cells become lymphoblasts
• Myeloblasts develop into eosinophils,
neutrophils, and basophils
• Monoblasts develop into monocytes
• Lymphoblasts develop into lymphocytes
Formation
of
Leukocytes
Platelets
• Fragments of megakaryocytes with a bluestaining outer region & purple granular center
• Granules contain serotonin, Ca2+, enzymes,
ADP, and platelet-derived growth factor (PDGF)
• Function in the clotting mechanism by forming a
temporary plug that helps seal breaks in blood
vessels
• Platelets not involved in clotting are kept
inactive by NO and prostaglandin I2
Genesis of Platelets
• Stem cell for platelets is the hemocytoblast
• Sequential developmental pathway is
hemocytoblast, megakaryoblast,
promegakaryocyte, megakaryocyte, and platelets
Summary of Formed Elements
Summary of Formed Elements
Table 17.2
III. Blood Types & IV.Blood Plasma
Learning Goals
1- Describe the ABO and Rh blood
grouping systems
2- Identify the major plasma components
and their generalized functions
Historical Perspective of Blood Typing
Around 1900, Karl Landsteiner discovered
that there are four different types of
human blood based on the presence or
absence of specific antigens found on the
surface of the red blood cells.
In 1940, Landsteiner and Weiner reported
the discovery of the Rh factor by studying
the blood of the Rhesus monkey. 85% of
Caucasians, 94% of Black Americans and
99% of all Asians are Rh positive.
A Review of Blood Terminology
• ABO blood groups—based on having an A, B,
both or no antigens on red blood cells
• Rh factor—may be present on red blood cells;
positive if present and negative if not
• Antigen—a substance that can stimulate the body
to make antibodies. Certain antigens (proteins)
found in the plasma of the red blood cell’s
membrane account for blood type.
• Antibody—a substance that reacts with an antigen
• Agglutination—clumping of red blood cells; will
result if blood types with different antigens are
mixed
Blood Typing
• Blood type A has antigen A on the surface
of the cell and will agglutinate with blood
type B.
• Blood type B has antigen B on the surface
of the cell and will agglutinate with blood
type A.
• Blood type AB has antigens A and B on the
surface of the cells and will not agglutinate
with either type A or B blood.
• Blood type O has neither antigen A or B and
will not agglutinate.
ABO Blood Groups
Table 17.4
Blood Groups
Antibody Can Give
Can Get
Blood From
Type
Antigen
A
A
B
A, AB
O, A
B
B
A
B, AB
O,B
AB
A and B
Neither
A nor B
AB
A, B, O, AB
O
Neither
A nor B
A and B
A, B, O, AB
O
Blood To
Population Distribution
of Blood Types in the U.S.
Type
Percent
O
45
A
40
B
11
AB
4
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
Blood Groups
• Humans have 30 varieties of naturally
occurring RBC antigens
• 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
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
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 becomes 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
Transfusion 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
V. Blood Clotting (Coagulation)
Learning Goal
1- Explain the mechanism of blood clotting
and the conditions that oppose and hasten
clotting
2- Mechanisms of disease involving blood
Hemostasis
• Series of reactions for stoppage of bleeding
• 3 phases occur in rapid sequence
– 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 blood vessel endothelium (which
exposes collagen) 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 PGI2
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
Steps of
Coagulation
Figure 17.13a
Detailed
Events of
Coagulation
Figure 17.13b
Coagulation Phase 1:
2 Pathways to Prothrombin Activator
• Initiated by either intrinsic or extrinsic pathway
– Triggered by tissue-damaging events
– Involves a series of procoagulants
– Each pathway cascades toward factor X
• 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
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
• Fibrin causes plasma to become a gel-like
trap
• Fibrin in the presence of calcium ions
activates factor XIII that:
– 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
– Stimulated by vascular endothelial growth
factor (VEGF), endothelial cells multiply and
restore the endothelial lining
Factors Limiting Clot Growth or Formation
• Two homeostatic mechanisms prevent
clots from becoming large
– 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
• Heparin, another anticoagulant, also inhibits
thrombin activity
Factors Preventing Undesirable 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
Erythrocyte Disorders
• Anemia – blood has abnormally low
oxygen-carrying 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
Erythrocytes
• 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:
– Deficiency of vitamin B12
– Lack of intrinsic factor needed for absorption of
B12
• Treatment is intramuscular injection of B12;
application of Nascobal
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)
– HbS has a single amino acid substitution in
the beta chain
– This defect causes RBCs to become sickleshaped in low oxygen situations
Polycythemia
• Polycythemia – excess RBCs that
increase blood viscosity
• Three main polycythemias are:
– Polycythemia vera
– Secondary polycythemia
– Blood doping