_ch_17_lecture_presentation.ppt

Human Anatomy & Physiology
Ninth Edition
PowerPoint® Lecture Slides
prepared by
Barbara Heard,
Atlantic Cape Community
College
C H A P T E R
© 2013 Pearson Education, Inc.
© Annie Leibovitz/Contact Press Images
Blood
17

Blood Composition
• Blood
– Fluid connective tissue
– Plasma – non-living fluid matrix
– Formed elements – living blood "cells"
suspended in plasma
• Erythrocytes (red blood cells, or RBCs)
• Leukocytes (white blood cells, or WBCs)
• Platelets

Blood Composition
• Spun tube of blood yields three layers
– Plasma on top (~55%)
– Erythrocytes on bottom (~45%)
– WBCs and platelets in Buffy coat (< 1%)
• Hematocrit
– Percent of blood volume that is RBCs
– 47% ± 5% for males; 42% ± 5% for females

Figure 17.1 The major components of whole blood.
Withdraw blood
and place in tube.
Centrifuge the
blood sample.
Plasma
• 55% of whole blood
• Least dense component
Buffy coat
• Leukocytes and platelets
• <1% of whole blood
Erythrocytes
(hematocrit)
• Most dense component
Formed
elements
Slide 1
2
1

Withdraw blood
and place in tube.
Slide 2
1

Withdraw blood
and place in tube.
Centrifuge the
blood sample.
Slide 3
2
1

Withdraw blood
and place in tube.
Centrifuge the
blood sample.
Plasma
• Least dense component
Buffy coat
• Leukocytes and platelets
• <1% of whole blood
Erythrocytes
(hematocrit)
• Most dense component
Formed
elements
Slide 4
2
1

Physical Characteristics and Volume
• Sticky, opaque fluid with metallic taste
• Color varies with O2 content
– High O2 - scarlet; Low O2 - dark red
• pH 7.35–7.45
• ~8% of body weight
• Average volume
– 5–6 L for males; 4–5 L for females

Functions of Blood
• Functions include
– Distributing substances
– Regulating blood levels of substances
– Protection

Distribution Functions
• Delivering O2 and nutrients to body cells
• Transporting metabolic wastes to lungs
and kidneys for elimination
• Transporting hormones from endocrine
organs to target organs

Regulation Functions
• Maintaining body temperature by
absorbing and distributing heat
• Maintaining normal pH using buffers;
alkaline reserve of bicarbonate ions
• Maintaining adequate fluid volume in
circulatory system

Protection Functions
• Preventing blood loss
– Plasma proteins and platelets initiate clot
formation
• Preventing infection
– Antibodies
– Complement proteins
– WBCs

Blood Plasma
• 90% water
• Over 100 dissolved solutes
– Nutrients, gases, hormones, wastes, proteins,
inorganic ions
– Plasma proteins most abundant solutes
• Remain in blood; not taken up by cells
• Proteins produced mostly by liver
• 60% albumin; 36% globulins; 4% fibrinogen

Table 17.1 Composition of Plasma (1 of 2)

Table 17.1 Composition of Plasma (2 of 2)

Albumin
• 60% of plasma protein
• Functions
– Substance carrier
– Blood buffer
– Major contributor of plasma osmotic pressure

Formed Elements
• Only WBCs are complete cells
• RBCs have no nuclei or other organelles
• Platelets are cell fragments
• Most formed elements survive in
bloodstream only few days
• Most blood cells originate in bone marrow
and do not divide

Figure 17.2 Photomicrograph of a human blood smear stained with Wright's stain.
Platelets Erythrocytes Monocyte
Neutrophils Lymphocyte

Erythrocytes
• Biconcave discs, anucleate, essentially no
organelles
• Diameters larger than some capillaries
• Filled with hemoglobin (Hb) for gas
transport
• Contain plasma membrane protein
spectrin and other proteins
– Spectrin provides flexibility to change shape
• Major factor contributing to blood viscosity

2.5 µm
7.5 µm
Top view
Side view (cut)
Figure 17.3 Structure of erythrocytes (red blood cells).

Erythrocytes
• Structural characteristics contribute to gas
transport
– Biconcave shape—huge surface area relative
to volume
– >97% hemoglobin (not counting water)
– No mitochondria; ATP production anaerobic;
do not consume O2 they transport
• Superb example of complementarity of
structure and function

Erythrocyte Function
• RBCs dedicated to respiratory gas
transport
• Hemoglobin binds reversibly with
oxygen
• Normal values
– Males - 13–18g/100ml; Females - 12–16
g/100ml

Hemoglobin Structure
• Globin composed of 4 polypeptide chains
– Two alpha and two beta chains
• Heme pigment bonded to each globin
chain
– Gives blood red color
• Heme's central iron atom binds one O2
• Each Hb molecule can transport four O2
• Each RBC contains 250 million Hb
molecules

Figure 17.4 Structure of hemoglobin.
 Globin chains
Heme
group
 Globin chains
Hemoglobin consists of globin (two alpha and two beta
polypeptide chains) and four heme groups.
Iron-containing heme pigment.

Hemoglobin (Hb)
• O2 loading in lungs
– Produces oxyhemoglobin (ruby red)
• O2 unloading in tissues
– Produces deoxyhemoglobin or reduced
hemoglobin (dark red)
• CO2 loading in tissues
– 20% of CO2 in blood binds to Hb 
carbaminohemoglobin

Hematopoiesis
• Blood cell formation in red bone marrow
– Composed of reticular connective tissue and
blood sinusoids
• In adult, found in axial skeleton, girdles,
and proximal epiphyses of humerus and
femur

Hematopoiesis
• Hematopoietic stem cells
(Hemocytoblasts)
– Give rise to all formed elements
– Hormones and growth factors push cell
toward specific pathway of blood cell
development
– Committed cells cannot change
• New blood cells enter blood sinusoids

Erythropoiesis: Red Blood Cell Production
• Stages
– Myeloid stem cell transformed into
proerythroblast
– In 15 days proerythroblasts develop into
basophilic, then polychromatic, then
orthochromatic erythroblasts, and then into
reticulocytes
– Reticulocytes enter bloodstream; in 2 days
mature RBC

Erythropoiesis
• As myeloid stem cell transforms
1. Ribosomes synthesized
2. Hemoglobin synthesized; iron accumulates
3. Ejection of nucleus; formation of reticulocyte
(young RBC)
• Reticulocyte ribosomes degraded; Then
become mature erythrocytes
• Reticulocyte count indicates rate of RBC
formation

Figure 17.5 Erythropoiesis: formation of red blood cells.
Stem cell Committed cell Developmental pathway
Phase 1
Ribosome synthesis
Phase 2
Hemoglobin accumulation
Phase 3
Ejection of nucleus
Hematopoietic stem
cell (hemocytoblast) Proerythroblast
Basophilic
erythroblast
Polychromatic
erythroblast
Orthochromatic
erythroblast Reticulocyte Erythrocyte

Regulation of Erythropoiesis
• Too few RBCs leads to tissue hypoxia
• Too many RBCs increases blood viscosity
• > 2 million RBCs made per second
• Balance between RBC production and
destruction depends on
– Hormonal controls
– Adequate supplies of iron, amino acids, and B
vitamins

Hormonal Control of Erythropoiesis
• Hormone Erythropoietin (EPO)
– Direct stimulus for erythropoiesis
– Always small amount in blood to maintain
basal rate
• High RBC or O2 levels depress production
– Released by kidneys (some from liver) in
response to hypoxia
• Dialysis patients have low RBC counts

• Causes of hypoxia
– Decreased RBC numbers due to hemorrhage
or increased destruction
– Insufficient hemoglobin per RBC (e.g., iron
deficiency)
– Reduced availability of O2 (e.g., high altitudes)

• Effects of EPO
– Rapid maturation of committed marrow cells
– Increased circulating reticulocyte count in 1–
2 days
• Some athletes abuse artificial EPO
– Dangerous consequences
• Testosterone enhances EPO production,
resulting in higher RBC counts in males

Stimulus:
Hypoxia
(inadequate O2
delivery) due to
O2-carrying
ability of blood
rises.
Enhanced
erythropoiesis
increases RBC count. Kidney (and liver to
a smaller extent)
releases
erythropoietin.
Erythropoietin
stimulates red
bone marrow.
Figure 17.6 Erythropoietin mechanism for regulating erythropoiesis.
Homeostasis: Normal blood oxygen levels
• Decreased
RBC count
• Decreased amount
of hemoglobin
• Decreased
availability of O2
Slide 1
1
2
3
4
5

Stimulus:
Hypoxia
(inadequate O2
delivery) due to
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Slide 2
1

Stimulus:
Hypoxia
(inadequate O2
delivery) due to
Kidney (and liver to
a smaller extent)
releases
erythropoietin.
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Slide 3
1
2

Stimulus:
Hypoxia
(inadequate O2
delivery) due to
a smaller extent)
releases
erythropoietin.
Erythropoietin
stimulates red
bone marrow.
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Slide 4
1
2
3

Stimulus:
Hypoxia
(inadequate O2
delivery) due to
a smaller extent)
releases
erythropoietin.
Erythropoietin
stimulates red
bone marrow.
Enhanced
erythropoiesis
increases RBC count.
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Slide 5
1
2
3
4

O2-carrying
ability of blood
rises.
Enhanced
erythropoiesis
increases RBC count.
Stimulus:
Hypoxia
(inadequate O2
delivery) due to
a smaller extent)
releases
erythropoietin.
Erythropoietin
stimulates red
bone marrow.
• Decreased
RBC count
of hemoglobin
• Decreased
availability of O2
Slide 6
1
2
3
4
5

Dietary Requirements for Erythropoiesis
• Nutrients—amino acids, lipids, and
carbohydrates
• Iron
– Available from diet
– 65% in Hb; rest in liver, spleen, and bone marrow
– Free iron ions toxic
• Stored in cells as ferritin and hemosiderin
• Transported in blood bound to protein transferrin
• Vitamin B12 and folic acid necessary for DNA
synthesis for rapidly dividing cells (developing
RBCs)

Fate and Destruction of Erythrocytes
• Life span: 100–120 days
– No protein synthesis, growth, division
• Old RBCs become fragile; Hb begins to
degenerate
• Get trapped in smaller circulatory channels
especially in spleen
• Macrophages engulf dying RBCs in spleen

Fate and Destruction of Erythrocytes
• Heme and globin are separated
– Iron salvaged for reuse
– Heme degraded to yellow pigment bilirubin
– Liver secretes bilirubin (in bile) into intestines
• Degraded to pigment urobilinogen
• Pigment leaves body in feces as stercobilin
– Globin metabolized into amino acids
• Released into circulation

Raw materials are
made available in blood
for erythrocyte synthesis.
Aged and damaged
red blood cells are engulfed
by macrophages of spleen,
liver, and bone marrow; the
hemoglobin is broken down.
New erythrocytes
enter bloodstream;
function about 120
days.
Erythropoietin and necessary
raw materials in blood promote
erythropoiesis in red bone marrow.
Erythropoietin levels rise in blood.
Low O2 levels in blood stimulate
kidneys to produce erythropoietin.
Figure 17.7 Life cycle of red blood cells.
Hemoglobin
Heme Globin
Bilirubin is
picked up
by the liver.
Iron is stored
as ferritin or
hemosiderin.
Amino
acids
Iron is bound to transferrin
and released to blood
from liver as needed
for erythropoiesis.
Bilirubin is secreted into
intestine in bile where
it is metabolized to
stercobilin by bacteria.
Circulation
Food nutrients
(amino acids, Fe,
B12, and folic acid)
are absorbed from
intestine and enter
blood.
Stercobilin
is excreted
in feces.
Slide 1
1
2
3
4
5
6

Slide 2
1

Slide 3
1
2

Slide 4
1
2
3

New erythrocytes
enter bloodstream;
function about 120
days.
Slide 5
1
2
3
4

Aged and damaged
5
Hemoglobin
Heme Globin
Bilirubin is
picked up
by the liver.
Iron is stored
as ferritin or
hemosiderin.
Amino
acids
Circulation
Slide 6

Raw materials are
Aged and damaged
Hemoglobin
Heme Globin
Bilirubin is
picked up
by the liver.
Iron is stored
as ferritin or
hemosiderin.
Amino
acids
for erythropoiesis.
Circulation
Food nutrients
(amino acids, Fe,
are absorbed from
intestine and enter
blood.
Stercobilin
is excreted
in feces.
Slide 7
5
6

Figure 17.7 Life cycle of red blood cells. Slide 8
Raw materials are
Aged and damaged
New erythrocytes
enter bloodstream;
function about 120
days.
Hemoglobin
Heme Globin
Bilirubin is
picked up
by the liver.
Iron is stored
as ferritin or
hemosiderin.
Amino
acids
for erythropoiesis.
Circulation
Food nutrients
(amino acids, Fe,
are absorbed from
intestine and enter
blood.
Stercobilin
is excreted
in feces.
1
2
3
4
5
6

Erythrocyte Disorders
• Anemia
– Blood has abnormally low O2-carrying
capacity
– Sign rather than disease itself
– Blood O2 levels cannot support normal
metabolism
– Accompanied by fatigue, pallor, shortness of
breath, and chills

Causes of Anemia
• Three groups
– Blood loss
– Low RBC production
– High RBC destruction

Causes of Anemia: Blood Loss
• Hemorrhagic anemia
– Blood loss rapid (e.g., stab wound)
– Treated by blood replacement
• Chronic hemorrhagic anemia
– Slight but persistent blood loss
• Hemorrhoids, bleeding ulcer
– Primary problem treated

Causes of Anemia: Low RBC Production
• Iron-deficiency anemia
– Caused by hemorrhagic anemia, low iron
intake, or impaired absorption
– Microcytic, hypochromic RBCs
– Iron supplements to treat

• Pernicious anemia
– Autoimmune disease - destroys stomach
mucosa
– Lack of intrinsic factor needed to absorb B12
• Deficiency of vitamin B12
– RBCs cannot divide  macrocytes
– Treated with B12 injections or nasal gel
– Also caused by low dietary B12 (vegetarians)

• Renal anemia
– Lack of EPO
– Often accompanies renal disease
– Treated with synthetic EPO

• Aplastic anemia
– Destruction or inhibition of red marrow by
drugs, chemicals, radiation, viruses
– Usually cause unknown
– All cell lines affected
• Anemia; clotting and immunity defects
– Treated short-term with transfusions; long-
term with transplanted stem cells

Causes of Anemia: High RBC Destruction
• Hemolytic anemias
– Premature RBC lysis
– Caused by
• Hb abnormalities
• Incompatible transfusions
• Infections

• Usually genetic basis for abnormal Hb
• Globin abnormal
– Fragile RBCs lyse prematurely

• Thalassemias
– Typically Mediterranean ancestry
– One globin chain absent or faulty
– RBCs thin, delicate, deficient in Hb
– Many subtypes
• Severity from mild to severe

• Sickle-cell anemia
– Hemoglobin S
• One amino acid wrong in a globin beta chain
– RBCs crescent shaped when unload O2 or
blood O2 low
– RBCs rupture easily and block small vessels
• Poor O2 delivery; pain

Sickle-cell Anemia
• Black people of African malarial belt and
descendants
• Malaria
– Kills 1 million each year
• Sickle-cell gene
– Two copies  Sickle-cell anemia
– One copy  Sickle-cell trait; milder disease;
better chance to survive malaria

Sickle-cell Anemia: Treatments
• Acute crisis treated with transfusions; inhaled
nitric oxide
• Preventing sickling
– Hydroxyurea induces fetal hemoglobin (which does
not sickle) formation
– Blocking RBC ion channels
– Stem cell transplants
– Gene therapy

Figure 17.8 Sickle-cell anemia.
Val His Leu Thr Pro Glu Glu …
1 2 3 4 5 6 7 146
Normal erythrocyte has normal
hemoglobin amino acid sequence
in the beta chain.
Val His Leu Thr Pro Val Glu …
1 2 3 4 5 6 7 146
Sickled erythrocyte results from a
single amino acid change in the
beta chain of hemoglobin.

Erythrocyte Disorders
• Polycythemia vera
– Bone marrow cancer  excess RBCs
– Severely increased blood viscosity
• Secondary polycythemia
– Less O2 available (high altitude) or EPO
production increases  higher RBC count
– Blood doping

Leukocytes
• Make up <1% of total blood volume
– 4,800 – 10,800 WBCs/μl blood
• Function in defense against disease
– Can leave capillaries via diapedesis
– Move through tissue spaces by ameboid
motion and positive chemotaxis
• Leukocytosis: WBC count over
11,000/mm3
– Normal response to infection

Leukocytes: Two Categories
• Granulocytes – Visible cytoplasmic
granules
– Neutrophils, eosinophils, basophils
• Agranulocytes – No visible cytoplasmic
granules
– Lymphocytes, monocytes
• Decreasing abundance in blood
– Never let monkeys eat bananas

Figure 17.9 Types and relative percentages of leukocytes in normal blood.
Formed
elements
(All total 4800–
10,800/ µl)
Granulocytes
Neutrophils (50–70%)
Eosinophils (2–4%)
Basophils (0.5–1%)
Agranulocytes
Lymphocytes (25–45%)
Monocytes (3–8%)
Platelets
Leukocytes
Erythrocytes
(not drawn
to scale)
Differential
WBC count

Granulocytes
• Granulocytes
– Larger and shorter-lived than RBCs
– Lobed nuclei
– Cytoplasmic granules stain specifically with
Wright's stain
– All phagocytic to some degree

Neutrophils
• Most numerous WBCs
• Also called Polymorphonuclear leukocytes
(PMNs or polys)
• Granules stain lilac; contain hydrolytic
enzymes or defensins
• 3-6 lobes in nucleus; twice size of RBCs
• Very phagocytic—"bacteria slayers"

Eosinophils
• Red-staining granules
• Bilobed nucleus
• Granules lysosome-like
– Release enzymes to digest parasitic worms
• Role in allergies and asthma
• Role in modulating immune response

Basophils
• Rarest WBCs
• Nucleus deep purple with 1-2 constrictions
• Large, purplish-black (basophilic) granules
contain histamine
– Histamine: inflammatory chemical that acts as
vasodilator to attract WBCs to inflamed sites
• Are functionally similar to mast cells

Figure 17.10a Leukocytes.
Granulocytes
Neutrophil:
Multilobed nucleus,
pale red and blue
cytoplasmic granules

Figure 17.10b Leukocytes.
Granulocytes
Eosinophil:
Bilobed nucleus, red

Figure 17.10c Leukocytes.
Granulocytes
Basophil:
Bilobed nucleus,
purplish-black

Agranulocytes
• Agranulocytes
– Lack visible cytoplasmic granules
– Have spherical or kidney-shaped nuclei

Lymphocytes
• Second most numerous WBC
• Large, dark-purple, circular nuclei with thin
rim of blue cytoplasm
• Mostly in lymphoid tissue (e.g., lymph
nodes, spleen); few circulate in blood
• Crucial to immunity

Lymphocytes
• Two types
– T lymphocytes (T cells) act against virus-
infected cells and tumor cells
– B lymphocytes (B cells) give rise to plasma
cells, which produce antibodies

Monocytes
• Largest leukocytes
• Abundant pale-blue cytoplasm
• Dark purple-staining, U- or kidney-shaped
nuclei

Monocytes
• Leave circulation, enter tissues, and
differentiate into macrophages
– Actively phagocytic cells; crucial against
viruses, intracellular bacterial parasites, and
chronic infections
• Activate lymphocytes to mount an immune
response

Agranulocytes
Lymphocyte (small):
Large spherical
nucleus, thin rim of
pale blue cytoplasm
Figure 17.10d Leukocytes.

Agranulocytes
Monocyte:
Kidney-shaped
nucleus, abundant
pale blue cytoplasm
Figure 17.10e Leukocytes.

Leukopoiesis
• Production of WBCs
– Stimulated by 2 types of chemical
messengers from red bone marrow and
mature WBCs
• Interleukins (e.g., IL-3, IL-5)
• Colony-stimulating factors (CSFs) named for WBC
type they stimulate (e.g., granulocyte-CSF
stimulates granulocytes)
• All leukocytes originate from
hemocytoblasts

Leukopoiesis
• Lymphoid stem cells  lymphocytes
• Myeloid stem cells  all others
• Progression of all granulocytes
– Myeloblast  promyelocyte  myelocyte 
band  mature cell
• Granulocytes stored in bone marrow
• 3 times more WBCs produced than RBCs
– Shorter life span; die fighting microbes

Leukopoiesis
• Progression of agranulocytes differs
• Monocytes – live several months
– Share common precursor with neutrophils
– Monoblast  promonocyte  monocyte
• Lymphocytes – live few hours to decades
– Lymphoid stem cell  T lymphocyte
precursors (travel to thymus) and B
lymphocyte precursors

Figure 17.11 Leukocyte formation.
Stem cells
Committed
cells
Developmental
pathway
Hematopoietic stem cell
(hemocytoblast)
Myeloid stem cell Lymphoid stem cell
Myeloblast Myeloblast Myeloblast Monoblast B lymphocyte
precursor
T lymphocyte
precursor
Promyelocyte Promyelocyte Promyelocyte Promonocyte
Eosinophilic
myelocyte
Basophilic
myelocyte
Neutrophilic
myelocyte
Eosinophilic
band cells
Basophilic
band cells
Neutrophilic
band cells
Granular
leukocytes
Agranular
leukocytes
Eosinophils Basophils Neutrophils Monocytes B lymphocytes T lymphocytes
Macrophages (tissues) Plasma cells Effector T cells
Some become Some become
(a) (b) (c) (d) (e) (f)
Some become

Leukocyte disorders
• Leukopenia
– Abnormally low WBC count—drug induced
• Leukemias – all fatal if untreated
– Cancer  overproduction of abnormal WBCs
– Named according to abnormal WBC clone involved
– Myeloid leukemia involves myeloblast descendants
– Lymphocytic leukemia involves lymphocytes
• Acute leukemia derives from stem cells;
primarily affects children
• Chronic leukemia more prevalent in older people

Leukemia
• Cancerous leukocytes fill red bone marrow
– Other lines crowded out  anemia; bleeding
• Immature nonfunctional WBCs in
bloodstream
• Death from internal hemorrhage;
overwhelming infections
• Treatments
– Irradiation, antileukemic drugs; stem cell
transplants

Infectious Mononucleosis
• Highly contagious viral disease
– Epstein-Barr virus
• High numbers atypical agranulocytes
• Symptoms
– Tired, achy, chronic sore throat, low fever
• Runs course with rest

Platelets
• Cytoplasmic fragments of
megakaryocytes
• Blue-staining outer region; purple granules
• Granules contain serotonin, Ca2+,
enzymes, ADP, and platelet-derived
growth factor (PDGF)
– Act in clotting process
• Normal = 150,000 – 400,000 platelets /ml
of blood

Platelets
• Form temporary platelet plug that helps
seal breaks in blood vessels
• Circulating platelets kept inactive and
mobile by nitric oxide (NO) and
prostacyclin from endothelial cells lining
blood vessels
• Age quickly; degenerate in about 10 days
• Formation regulated by thrombopoietin
• Derive from megakaryoblast
– Mitosis but no cytokinesis  megakaryocyte
- large cell with multilobed nucleus

Figure 17.12 Formation of platelets.
Stem cell Developmental pathway
Hematopoietic stem
cell (hemocytoblast)
Megakaryoblast
(stage I megakaryocyte)
Megakaryocyte
(stage II/III)
Megakaryocyte
(stage IV)
Platelets

Table 17.2 Summary of Formed Elements of the Blood (1 of 2)

Table 17.2 Summary of Formed Elements of the Blood (2 of 2)

Hemostasis
• Fast series of reactions for stoppage of
bleeding
• Requires clotting factors, and
substances released by platelets and
injured tissues
• Three steps
1. Vascular spasm
2. Platelet plug formation
3. Coagulation (blood clotting)

Hemostasis: Vascular Spasm
• Vasoconstriction of damaged blood vessel
• Triggers
– Direct injury to vascular smooth muscle
– Chemicals released by endothelial cells and
platelets
– Pain reflexes
• Most effective in smaller blood vessels

Hemostasis: Platelet Plug Formation
• Positive feedback cycle
• Damaged endothelium exposes collagen
fibers
– Platelets stick to collagen fibers via plasma
protein von Willebrand factor
– Swell, become spiked and sticky, and release
chemical messengers
• ADP causes more platelets to stick and release
their contents
• Serotonin and thromboxane A2 enhance vascular
spasm and platelet aggregation

Hemostasis: Coagulation
• Reinforces platelet plug with fibrin threads
• Blood transformed from liquid to gel
• Series of reactions using clotting factors
(procoagulants)
– # I – XIII; most plasma proteins
– Vitamin K needed to synthesize 4 of them

Figure 17.13 Events of hemostasis. Slide 1
Step 1 Vascular spasm
• Smooth muscle contracts,
causing vasoconstriction.
Step 2 Platelet plug
formation
• Injury to lining of vessel
exposes collagen fibers;
platelets adhere.
• Platelets release chemicals
that make nearby platelets
sticky; platelet plug forms.
Step 3 Coagulation
• Fibrin forms a mesh that traps
red blood cells and platelets,
forming the clot.
Collagen
fibers
Platelets
Fibrin

formation
platelets adhere.
Collagen
fibers

formation
platelets adhere.
Collagen
fibers
Platelets

formation
platelets adhere.
Step 3 Coagulation
• Fibrin forms a mesh that traps
red blood cells and platelets,
forming the clot.
Collagen
fibers
Platelets
Fibrin

Coagulation: Overview
• Three phases of coagulation
– Prothrombin activator formed in both
intrinsic and extrinsic pathways
– Prothrombin converted to enzyme thrombin
– Thrombin catalyzes fibrinogen  fibrin

Coagulation Phase 1: Two Pathways to
Prothrombin Activator
• Initiated by either intrinsic or extrinsic
pathway (usually both)
– Triggered by tissue-damaging events
– Involves a series of procoagulants
– Each pathway cascades toward factor X
• Factor X complexes with Ca2+, PF3, and
factor V to form prothrombin activator

Coagulation Phase 1: Two Pathways to
Prothrombin Activator
• Intrinsic pathway
– Triggered by negatively charged surfaces
(activated platelets, collagen, glass)
– Uses factors present within blood (intrinsic)
• Extrinsic pathway
– Triggered by exposure to tissue factor (TF) or
factor III (an extrinsic factor)
– Bypasses several steps of intrinsic pathway,
so faster

Coagulation Phase 2: Pathway to Thrombin
• Prothrombin activator catalyzes
transformation of prothrombin to active
enzyme thrombin
• Once prothrombin activator formed, clot
forms in 10–15 seconds

Coagulation Phase 3: Common Pathway to
the Fibrin Mesh
• Thrombin converts soluble fibrinogen to
fibrin
• Fibrin strands form structural basis of clot
• Fibrin causes plasma to become a gel-like
trap for formed elements
• Thrombin (with Ca2+) activates factor XIII
which:
– Cross-links fibrin
– Strengthens and stabilizes clot

Figure 17.14 The intrinsic and extrinsic pathways of blood clotting (coagulation). (1 of 2)
Intrinsic pathway Extrinsic pathway
Vessel endothelium
ruptures, exposing
underlying tissues
(e.g., collagen)
Tissue cell trauma
exposes blood to
Platelets cling and their
surfaces provide sites for
mobilization of factors
Tissue factor (TF)
XII
XIIa
Ca2+
VII
XI
XIa
IX Ca2+
VIIa
IXa
VIII
VIIIa
IXa/VIIIa complex TF/VIIa complex
X
Xa
Ca2+
PF3
Va V
Prothrombin
activator
PF3
released by
aggregated
platelets
Phase 1

Figure 17.14 The intrinsic and extrinsic pathways of blood clotting (coagulation). (2 of 2)
Phase 2
Prothrombin (II)
Thrombin (IIa)
Phase 3
Fibrinogen (I)
(soluble)
Fibrin
(insoluble
polymer)
Cross-linked
fibrin mesh
XIIIa
XIII
Ca2+

Figure 17.15 Scanning electron micrograph of erythrocytes trapped in a fibrin mesh.

Clot Retraction
• Stabilizes clot
• Actin and myosin in platelets contract
within 30–60 minutes
• Contraction pulls on fibrin strands,
squeezing serum from clot
• Draws ruptured blood vessel edges
together

Vessel Repair
• Vessel is healing as clot retraction occurs
• Platelet-derived growth factor (PDGF)
stimulates division of smooth muscle cells
and fibroblasts to rebuild blood vessel wall
• Vascular endothelial growth factor (VEGF)
stimulates endothelial cells to multiply and
restore endothelial lining

Fibrinolysis
• Removes unneeded clots after healing
• Begins within two days; continues for
several
• Plasminogen in clot is converted to
plasmin by tissue plasminogen activator
(tPA), factor XII and thrombin
• Plasmin is a fibrin-digesting enzyme

Factors Limiting Clot Growth or Formation
• Two mechanisms limit clot size
– Swift removal and dilution of clotting factors
– Inhibition of activated clotting factors
• Thrombin bound onto fibrin threads
• Antithrombin III inactivates unbound
thrombin
• Heparin in basophil and mast cells inhibits
thrombin by enhancing antithrombin III

Factors Preventing Undesirable Clotting
• Platelet adhesion is prevented by
– Smooth endothelium of blood vessels
prevents platelets from clinging
– Antithrombic substances nitric oxide and
prostacyclin secreted by endothelial cells
– Vitamin E quinone acts as potent
anticoagulant

Disorders of Hemostasis
• Thromboembolic disorders: undesirable
clot formation
• Bleeding disorders: abnormalities that
prevent normal clot formation
• Disseminated intravascular coagulation
(DIC)
– Involves both types of disorders

Thromboembolic Conditions
• Thrombus: clot that develops and persists
in unbroken blood vessel
– May block circulation leading to tissue death
• Embolus: thrombus freely floating in
bloodstream
• Embolism: embolus obstructing a vessel
– E.g., pulmonary and cerebral emboli
• Risk factors – atherosclerosis,
inflammation, slowly flowing blood or blood
stasis from immobility

Anticoagulant Drugs
• Aspirin
– Antiprostaglandin that inhibits thromboxane A2
• Heparin
– Anticoagulant used clinically for pre- and
postoperative cardiac care
• Warfarin (Coumadin)
– Used for those prone to atrial fibrillation
– Interferes with action of vitamin K
• Dabigatran directly inhibits thrombin

Bleeding Disorders
• Thrombocytopenia: deficient number of
circulating platelets
– Petechiae appear due to spontaneous,
widespread hemorrhage
– Due to suppression or destruction of red bone
marrow (e.g., malignancy, radiation, drugs)
– Platelet count <50,000/μl is diagnostic
– Treated with transfusion of concentrated
platelets

Bleeding Disorders
• Impaired liver function
– Inability to synthesize procoagulants
– Causes include vitamin K deficiency,
hepatitis, and cirrhosis
– Impaired fat absorption and liver disease can
also prevent liver from producing bile,
impairing fat and vitamin K absorption

Bleeding Disorders
• Hemophilia includes several similar hereditary
bleeding disorders
– Hemophilia A: most common type (77% of all cases);
factor VIII deficiency
– Hemophilia B: factor IX deficiency
– Hemophilia C: mild type; factor XI deficiency
• Symptoms include prolonged bleeding,
especially into joint cavities
• Treated with plasma transfusions and injection
of missing factors
– Increased hepatitis and HIV risk

Disseminated Intravascular Coagulation
(DIC)
• Clotting causes bleeding
– Widespread clotting blocks intact blood
vessels
– Severe bleeding occurs because residual
blood unable to clot
• Occurs as pregnancy complication; in
septicemia, or incompatible blood
transfusions

Transfusions
• Whole-blood transfusions used when
blood loss rapid and substantial
• Packed red cells (plasma and WBCs
removed) transfused to restore oxygen-
carrying capacity
• Transfusion of incompatible blood can be
fatal

Human Blood Groups
• RBC membranes bear 30 types of glycoprotein
antigens
– Anything perceived as foreign; generates an immune
response
– Promoters of agglutination; called agglutinogens
• Mismatched transfused blood perceived as
foreign
– May be agglutinated and destroyed; can be fatal
• Presence or absence of each antigen is used to
classify blood cells into different groups

Blood Groups
• Antigens of ABO and Rh blood groups
cause vigorous transfusion reactions
• Other blood groups (MNS, Duffy, Kell, and
Lewis) usually weak agglutinogens

ABO Blood Groups
• Types A, B, AB, and O
• Based on presence or absence of two
agglutinogens (A and B) on surface of
RBCs
• Blood may contain preformed anti-A or
anti-B antibodies (agglutinins)
– Act against transfused RBCs with ABO
antigens not present on recipient's RBCs
• Anti-A or anti-B form in blood at about
2 months of age; adult levels by 8-10

Table 17.4 ABO Blood Groups

Rh Blood Groups
• 52 named Rh agglutinogens (Rh factors)
• C, D, and E are most common
• Rh+ indicates presence of D antigen
– 85% Americans Rh+

Rh Blood Groups
• Anti-Rh antibodies not spontaneously
formed in Rh– individuals
– Anti-Rh antibodies form if Rh– individual
receives Rh+ blood, or Rh– mom carrying Rh+
fetus
• Second exposure to Rh+ blood will result
in typical transfusion reaction

Homeostatic Imbalance: Hemolytic Disease
of the Newborn
• Also called erythroblastosis fetalis
– Only occurs in Rh– mom with Rh+ fetus
• Rh– mom exposed to Rh+ blood of fetus
during delivery of first baby – baby healthy
– Mother synthesizes anti-Rh antibodies
• Second pregnancy
– Mom's anti-Rh antibodies cross placenta and
destroy RBCs of Rh+ baby

Homeostatic Imbalance: Hemolytic Disease
of the Newborn
• Baby treated with prebirth transfusions
and exchange transfusions after birth
• RhoGAM serum containing anti-Rh can
prevent Rh– mother from becoming
sensitized

Transfusion Reactions
• Occur if mismatched blood infused
• Donor's cells
– Attacked by recipient's plasma agglutinins
– Agglutinate and clog small vessels
– Rupture and release hemoglobin into
bloodstream
• Result in
– Diminished oxygen-carrying capacity
– Diminished blood flow beyond blocked
vessels
– Hemoglobin in kidney tubules  renal failure

Transfusion Reactions
• Symptoms
– Fever, chills, low blood pressure, rapid
heartbeat, nausea, vomiting
• Treatment
– Preventing kidney damage
• Fluids and diuretics to wash out hemoglobin

Transfusions
• Type O universal donor
– No A or B antigens
• Type AB universal recipient
– No anti-A or anti-B antibodies
• Misleading - other agglutinogens cause
transfusion reactions
• Autologous transfusions
– Patient predonates

Before Transfusion
• Blood typing
– Mixing RBCs with antibodies against its
agglutinogen(s) causes clumping of RBCs
– Done for ABO and for Rh factor
• Cross matching
– Mix recipient's serum with donor RBCs
– Mix recipient's RBCs with donor serum

Figure 17.16 Blood typing of ABO blood types.
Blood being tested Serum
Anti-A Anti-B
Type AB (contains
agglutinogens A and B;
agglutinates with both
sera)
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)
RBCs

Restoring Blood Volume
• Death from shock may result from low
blood volume
• Volume must be replaced immediately
with
– Normal saline or multiple-electrolyte solution
(Ringer's solution) that mimics plasma
electrolyte composition
– Plasma expanders (e.g., purified human
serum albumin, hetastarch, and dextran)
• Mimic osmotic properties of albumin
• More expensive and may cause significant
complications

Diagnostic Blood Tests
• Hematocrit – test for anemia
• Blood glucose tests – diabetes
• Microscopic examination reveals
variations in size and shape of RBCs,
indications of anemias

Diagnostic Blood Tests
• Differential WBC count
• Prothrombin time and platelet counts
assess hemostasis
• SMAC, a blood chemistry profile – liver
and kidney disorders
• Complete blood count (CBC) – checks
formed elements, hematocrit, hemoglobin

Developmental Aspects
• Fetal blood cells form in fetal yolk sac,
liver, and spleen
• Red bone marrow is primary
hematopoietic area by seventh month
• Blood cells develop from mesenchymal
cells called blood islands
• The fetus forms Hemoglobin F, which has
higher affinity for O2 than hemoglobin A
formed after birth

Developmental Aspects
• Blood diseases of aging
– Chronic leukemias, anemias, clotting
disorders
– Usually precipitated by disorders of heart,
blood vessels, or immune system

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