Chapter 18
Lecture Outline
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1
18.1
Functions and
General Composition
of Blood
Learning
Objectives:
1.
Describe the general functions of
blood.
2.
Name six characteristics that
describe blood, and explain the
significance of each to health and
homeostasis.
3.
List the three components of a
centrifuged blood sample.
4.
Define hematocrit, and explain how
the medical definition differs from
the clinical usage.
5.
Name the three formed elements of
the blood, and compare their
relative abundance.
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2
18.1 Functions and General
Composition of Blood
• Blood
– Continuously regenerated connective tissue
– Moves gases, nutrients, wastes, and hormones
– Transported through cardiovascular system
o Heart pumps blood
o Arteries transport blood away from heart
o Veins transport blood toward heart
o Capillaries allow exchange between blood and body tissues
3
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18.1 Functions and General
Composition of Blood
• Blood components: formed elements and plasma
– Formed elements
o Erythrocytes (red blood cells) transport respiratory gases in the blood
o Leukocytes (white blood cells) defend against pathogens
o Platelets help form clots to prevent blood loss
– Plasma: fluid portion of blood
o Contains plasma proteins and dissolved solutes
4
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18.1a Functions of Blood
• Transportation
– Transports formed elements, dissolved molecules and ions
o Carries oxygen from and carbon dioxide to the lungs
o Transports nutrients, hormones, heat and waste products
• Protection
– Leukocytes, plasma proteins, and other molecules (of immune
system) protect against pathogens
– Platelets and certain plasma proteins protect against blood loss
5
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18.1a Functions of Blood
• Regulation of body conditions
– Body temperature
o Blood absorbs heat from body cells (especially muscle)
o Heat released at skin blood vessels
– Body pH
o Blood absorbs acid and base from body cells
o Blood contains chemical buffers
– Fluid balance
o Water is added to blood from GI tract
o Water lost through urine, skin, respiration
o Fluid is exchanged between blood and interstitial fluid
– Blood contains proteins and ions helping maintain osmotic balance
6
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18.1b Physical Characteristics of Blood
• Blood color depends on degree of oxygenation
– Oxygen-rich blood is bright red
– Oxygen-poor blood is dark red
• Volume = about 5 liters in adult
– On average, males have slightly more than females (due to
body size)
• Viscosity: blood is 4–5 times thicker than water
– Depends on amount of dissolved and suspended substances
relative to amount of fluid
o Viscosity increases if erythrocyte number increases
o Viscosity increases if amount of fluid decreases
7
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18.1b Physical Characteristics of Blood
• Plasma concentration of solutes (e.g., proteins, ions)
– Determines the direction of osmosis across capillary walls
o E.g., during dehydration plasma hypertonic: fluid drawn from tissues
• Temperature
– Blood is 1°C higher than measured body temperature
o Warms area through which it travels
• Blood pH is slightly alkaline
– pH between 7.35 and 7.45
– Crucial for normal plasma protein shape (avoiding denaturation)
8
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18.1c Components of Blood
• Centrifuged blood
– Whole blood (plasma and formed elements) separated
into parts by centrifuge
– Plasma
o Straw-colored liquid at top of tube
o About 55% of sample
– Buffy coat
o Very thin (1%) middle layer with gray-white color
o Composed of leukocytes and platelets
– Erythrocytes
o Lower, red layer
o About 44% of sample
Fig 18.1 (part)
9
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Centrifuged Blood
Figure 18.1
10
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18.1c Components of Blood
• Centrifuged blood (continued)
– Hematocrit
o Percentage of volume of all formed elements
o Clinical definition: percentage of only erythrocytes
o Adult males: 42–56%; females 38–46%
– Males have more RBCs because testosterone causes more erythropoietin
secretion by kidney
11
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18.1c Components of Blood
• Blood smear
– Thin layer of blood placed on microscope slide and stained
– Formed elements differ in appearance
o Erythrocytes are most numerous
– Pink, anucleate, biconcave discs
o Leukocytes
– Larger than erythrocytes, varied in form
– Noticeable nucleus
o Platelets
– Small fragments of cells
12
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Blood Smear
Figure 18.2
13
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What did you
learn?
•
What are the functions of
erythrocytes and leukocytes?
•
Would a hematocrit of 39%
be considered normal?
•
What is the pH of blood and
why does it matter?
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14
18.2
Composition of
Blood Plasma
Learning
Objectives:
1.
Define colloid osmotic pressure.
2.
Identify the various types of plasma
proteins, and explain the general
function of each.
3.
List dissolved substances in plasma
by category.
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15
18.2 Composition of Blood Plasma
• Plasma
– Composed of
o Water (92%)
o Plasma proteins (7%)
o Dissolved molecules and ions (1%)
– It is an extracellular fluid
– Similar composition to interstitial fluid, but plasma has
higher protein concentration
16
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18.2a Plasma Proteins
• Blood is a colloid
– Plasma contains dispersed proteins
• There are a variety of plasma proteins
– Albumin, globulins, fibrinogen and other clotting proteins,
enzymes, and some hormones
– Most produced in the liver
o Others produced by leukocytes or other organs
17
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18.2a Plasma Proteins
• Plasma proteins exert colloid osmotic pressure
– Prevents loss of fluid from blood as it moves through
capillaries
o Helps maintain blood volume and blood pressure
– Can be decreased with diseases, resulting in fluid loss from
blood and tissue swelling
o E.g., liver diseases that decrease production of plasma proteins
o E.g., kidney diseases that increase elimination of plasma proteins
18
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18.2a Plasma Proteins
• Albumins
– Smallest and most abundant group of plasma proteins (58%)
– Exert greatest colloid osmotic pressure
– Act as transport proteins for some lipids, hormones, and ions
• Globulins
– Second largest group of plasma proteins (37%)
– Smaller alpha-globulins and larger beta-globulins
o Transport some water-insoluble molecules, hormones, metals, ions
– Gamma-globulins (immunoglobulins or antibodies)
o Part of body’s defenses
19
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18.2a Plasma Proteins
• Fibrinogen
– Makes up only 4% of plasma proteins
– Contributes to blood clot formation
o Following trauma, it is converted to insoluble fibrin strands
– Serum is plasma with clotting proteins removed
• Regulatory proteins
– Less than 1% of total proteins
– Includes enzymes and hormones
20
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18.2b Other Solutes
• Blood also considered a solution
–
–
–
–
Contains dissolved organic and inorganic molecules and ions
Include electrolytes, nutrients, gases, waste products
Polar or charged substances dissolve easily
Nonpolar molecules require carrier proteins
21
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What did you
learn?
•
Would a malnourished person
eating inadequate amounts of
protein have blood with high
or low colloid osmotic
pressure?
•
What functions do albumins
serve?
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22
18.3
Formed
Elements in the
Blood
1.
2.
3.
Learning
Objectives:
4.
5.
6.
Define hemopoiesis, and explain the
role of colony-stimulating factors.
Describe the four cellular stages of
erythropoiesis.
Compare the production of
granulocytes, monocytes, and
lymphocytes in leukopoiesis.
Summarize the process by which
platelets are formed in
thrombopoiesis.
Describe the structure of
erythrocytes.
List the events by which erythrocyte
production is stimulated.
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23
18.3
Formed Elements
in the Blood
(continued)
Learning
Objectives:
Explain the process by which
erythrocyte components are recycled.
8. Compare and contrast the different
blood types and their importance
when transfusing blood.
9. Explain the main function of
leukocytes.
10. Distinguish between granulocytes and
agranulocytes, and compare and
contrast the various types.
11. Explain what is meant by a
differential count and how it is
clinically useful.
12. Explain the structure and function of
platelets.
7.
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24
18.3a Hemopoiesis
• Hemopoiesis: production of formed elements
– Occurs in red bone marrow of certain bones
– Hemocytoblasts: stem cells
o Pluripotent: can differentiate into many types of cells
o Produce two different lines: myeloid line and lymphoid line
o Myeloid line forms erythrocytes, all leukocytes except lymphocytes,
and megakaryocytes (cells that produce platelets)
o Lymphoid line forms only lymphocytes
25
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18.3a Hemopoiesis
• Colony-stimulating factors (CSFs) stimulate hemopoiesis
– Multi-colony-stimulating factor (multi-CSF)
o Increases formation of erythrocytes, granulocytes, monocytes, and platelets
– Granulocyte-macrophage colony-stimulating factor (GM-CSF)
o Accelerates formation of granulocytes and monocytes
– Granulocyte colony-stimulating factor (G-CSF)
o Stimulates formation of granulocytes
– Macrophage colony-stimulating factor (M-CSF)
o Stimulates production of monocytes
– Thrombopoietin
o Stimulates production of platelets
– Erythropoietin (EPO): hormone from kidneys (rest are growth factors)
o Increases rate of production and maturation of erythrocytes
26
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18.3a Hemopoiesis
• Erythropoiesis: red blood cell production
–
–
–
–
–
–
Process requires iron, B vitamins, amino acids
Begins with myeloid stem cell—responds to multi-CSF
Forms progenitor cell
Forms proerythroblast—a large nucleated cell
Becomes erythroblast—smaller, produces hemoglobin
Becomes normoblast—still smaller, more hemoglobin,
anucleate
– Becomes reticulocyte—lacks organelles except ribosomes that
make hemoglobin
– Becomes erythrocyte—ribosomes have degenerated
27
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18.3a Hemopoiesis
• Leukopoiesis: production of leukocytes
– Involves maturation of granulocytes, monocytes, lymphocytes
– Granulocytes are neutrophils, basophils, and eosinophils
o Multi-CSF and GM-CSF cause myeloid stem cell to form progenitor cell
o Progenitor cell becomes myeloblast that becomes a granulocyte
– Monocytes also derived from myeloid stem cells
o Stem cell differentiates into progenitor cell
o M-CSF prompts progenitor cell to become a monoblast
o Monoblast becomes a promonocyte, which matures into a monocyte
28
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18.3a Hemopoiesis
• Leukopoiesis (continued)
– Lymphocytes are derived from lymphoid stem cells
o Stem cells differentiate into B-lymphoblasts and T-lymphoblasts
o Lymphoblasts mature into B-lymphocytes and T-lymphocytes
o Some lymphoid stem cells differentiate directly into natural killer
cells
29
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18.3a Hemopoiesis
• Thrombopoiesis: platelet production
– Megakaryoblast produced from myeloid stem cell
– Forms megakaryocyte under influence of thrombopoietin
o Large size and multilobed nucleus
– Megakaryocyte produces thousands of platelets
o Large cell produces proplatelets—long extensions
o These extend through blood vessel wall into bloodstream
o Blood flow “slices” off fragments which are platelets
30
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Origin,
Differentiation,
and
Maturation
of Formed
Elements
Figure 18.3
31
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Platelet
Formation
Figure 18.4
32
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18.3b Erythrocytes
• Erythrocytes (red blood cells)
– Small, flexible formed elements
– Lack nucleus and cellular organelles; packed with hemoglobin
– Have biconcave disc structure
o Has latticework of spectrin protein providing support and flexibility
o Can stack and line up in single file, rouleau
– Transport oxygen and carbon dioxide between tissues and lungs
Figure 18.5
33
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18.3b Erythrocytes
• Hemoglobin: red-pigmented protein
–
–
–
–
Transports oxygen and carbon dioxide
Termed oxygenated when maximally loaded with oxygen
Termed deoxygenated when some oxygen lost
Each hemoglobin molecule is composed of four globins
o Two alpha chains and two beta chains
o Each chain has a heme group: a porphyrin ring with an iron ion in its
center
– Oxygen binds to the iron ion, so each hemoglobin can bind four oxygen
molecules
34
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18.3b Erythrocytes
• Hemoglobin (continued)
– Oxygen binds to iron
o Binding is fairly weak
o Rapid attachment in lungs and rapid detachment in body tissues
– Carbon dioxide binds to globin protein (not iron)
o Binding is fairly weak
o Attachment in body tissue and detachment in lungs
35
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Molecular
Structure of
Hemoglobin
Figure 18.6
36
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18.3b Erythrocytes
• Erythropoietin (EPO) controls erythropoiesis
– EPO is a hormone produced primarily in the kidneys
o Liver produces just a little EPO
– EPO secretion is stimulated by a decrease in blood oxygen
– Red marrow myeloid cells respond to EPO by making more
erythrocytes and releasing them into circulation
– The erythrocytes increase blood’s oxygen carrying capacity
o The increase in blood oxygen inhibits EPO release (negative feedback)
37
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18.3b Erythrocytes
• EPO controls erythropoiesis (continued)
– Testosterone stimulates EPO production in kidney
o Males have higher testosterone and higher erythrocyte count, higher
hematocrit
– Environmental factors such as altitude influence EPO levels
o The low oxygen levels at high altitude stimulate EPO production
o Increased erythropoiesis raises blood’s oxygen carrying capacity and
viscosity
38
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How EPO Regulates Erythrocyte Production (Figure 18.7)
39
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Clinical View: Blood Doping
• Used by some athletes to enhance performance
• One method, self donation of erythrocytes
– Blood removal prior to competition increases EPO production
– Erythrocytes transfused back prior to competition
• Second method: pharmaceutical EPO
• Dangers
–
–
–
–
Increased blood viscosity
Heart required to work harder
May cause permanent cardiovascular damage
Banned from athletic competition
40
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18.3b Erythrocytes
• Erythrocyte destruction
– Lacking organelles, erythrocytes cannot synthesize proteins for
repairs
– Maximum life span is120 days
o Old erythrocytes phagocytized in spleen or liver
– Globins and membrane proteins are broken into amino acids
o Used by body for protein synthesis
– Iron from hemoglobin transported by transferrin protein to liver
o Bound to storage proteins: ferritin, hemosiderin
o Most is bound to ferritin and stored in liver and spleen
o Transported to red bone marrow as needed for erythrocyte production
41
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18.3b Erythrocytes
• Erythrocyte destruction (continued)
– Heme group (minus Fe2+ )
o Converted within macrophages into green pigment, biliverdin
o Eventually converted into yellowish pigment, bilirubin
– Transported by albumin to liver
– Becomes part of bile (used in digestive system)
o Bilirubin converted to urobilinogen in small intestine
– May continue thorough intestine, be converted by bacteria to stercobilin,
and be expelled from body as brown pigment in feces
– May be absorbed back into blood, converted to urobilin, and be excreted
from kidneys as yellow pigment of urine
42
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Erythrocyte Recycling
Figure 18.8
43
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Erythrocyte Recycling
Figure 18.8 continued
44
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Clinical View: Anemia
• Either the percentage of erythrocytes is lower than
normal or the oxygen-carrying capacity is reduced
– Symptoms: lethargy, shortness of breath, pallor, palpitations
– Causes
o Decreased or abnormal erythrocyte formation
o Heavy blood loss
o Deficiency of iron, vitamin B12, or folic acid
o Genetic defects
– Some cases can be treated by pharmaceutical EPO
– Sometimes signals underlying problem
o E.g., undiagnosed stomach ulcer
45
18.3b Erythrocytes
• Blood types
– Blood group depends on surface antigens projecting from
erythrocyte membrane
• ABO blood group
– Determined by presence or absence of A antigen and B antigen
o A and B antigens are membrane glycoproteins
–
–
–
–
Type A blood: erythrocytes have antigen A
Type B blood: erythrocytes have antigen B
Type AB blood: erythrocytes have both antigens
Type O blood: erythrocytes have neither antigen
46
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18.3b Erythrocytes
• ABO blood group (continued)
– A person’s antigen status determines their antibody status
o A person doesn’t have antibodies for their own surface proteins
o A person does have antibodies to antigens that are foreign to them
–
–
–
–
Type A blood has anti-B antibodies in its plasma
Type B blood has anti-A antibodies in its plasma
Type AB blood has neither antibodies
Type O blood has both antibodies in its plasma
47
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ABO Blood Types
(Figure 18.9a)
48
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18.3b Erythrocytes
• Rh blood type
– Presence or absence of Rh factor
(antigen D) on erythrocytes
determines if blood type is
positive or negative
– Antibodies to Rh factor (anti-D
antibodies) not usually there
o Only appear after Rh negative
person exposed to Rh positive
blood
– ABO group and Rh type are
reported together
o E.g. if all 3 antigens are present,
blood type is described as AB+
Figure 18.9b
49
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18.3b Erythrocytes
• Clinical concerns about blood types
– If someone receives an incompatible transfusion
agglutination occurs
o Recipient’s antibodies bind to transfused erythrocytes and clump them
together
o Can block blood vessels and prevent normal circulation
o Can cause hemolysis, rupture of erythrocytes, organ damage
50
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Agglutination Reaction
Figure 18.10a
51
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Agglutination Reaction
Figure 18.10b
52
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Clinical View: Rh Incompatibility and Pregnancy
• Rh negative mom
– May be exposed to Rh+ blood during childbirth of Rh+ baby
– Mom now with anti-D antibodies
– In future pregnancy, may cross placenta, destroy fetal RBCs
• Results in hemolytic disease of the newborn
– Infant with anemia and hyperbilirubinemia, heart failure
– Prevention:
o Give pregnant Rh negative woman special immunoglobulins
53
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18.3c Leukocytes
• Leukocyte characteristics
– Defend against pathogens
– Contain nucleus and organelles, but not hemoglobin
– Motile and flexible—most not in blood but in tissues
o Diapedesis: process of squeezing through blood vessel wall
o Chemotaxis: attraction of leukocytes to chemicals at an infection site
54
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18.3c Leukocytes
55
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18.3c Leukocytes
• Leukocyte types: granulocytes or agranuloctyes
– Granulocytes have visible granules seen with light
microscope
o Neutrophils, eosinophils, basophils
– Agranulocytes have smaller granules that are not visible
with light microscope
o Lymphocytes, monocytes
56
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18.3c Leukocytes
Granulocytes
• Neutrophils (polymorphonuclear leukocytes)
–
–
–
–
Most numerous leukocyte in blood
Multilobed nucleus
Cytoplasm has pale granules when stained
Enter tissue spaces and phagocytize infectious pathogens
o Numbers rise dramatically in chronic bacterial infection
57
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18.3c Leukocytes
Granulocytes (continued)
• Eosinophils
–
–
–
–
–
1–4% of leukocytes
Bilobed nucleus connected by thin strand
Cytoplasm has reddish granules
Phagocytize antigen-antibody complexes or allergens
Active in cases of parasitic worm infection
58
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18.3c Leukocytes
Granulocytes (continued)
• Basophils
– 0.5–1% of leukocytes
– Bilobed nucleus
– Cytoplasm has blue-violet granules with histamine and
heparin
o Histamine release causes increase in blood vessel diameter and
capillary permeability (classic allergy symptoms)
o Heparin release inhibits blood clotting
59
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18.3c Leukocytes
Agranulocytes
• Lymphocytes
–
–
–
–
Reside in lymphatic organs and structures
20–40% of blood leukocytes
Dark-staining round nucleus
Three categories
o T-lymphocytes manage immune response
o B-lymphocytes become plasma cells and produce antibodies
o NK cells (natural killer cells) attack abnormal and infected tissue
cells
60
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18.3c Leukocytes
Agranulocytes (continued)
• Monocytes
– C-shaped nucleus
– 2–8% of blood leukocytes
– Take up residence in tissues
o Transform into large phagocytic cells, macrophages
o Phagocytize bacteria, viruses, debris
61
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18.3c Leukocytes
• Differential count and changes in leukocyte profiles
– Leukopenia: reduced number of leukocytes
o Increases risk of infection
– Leukocytosis: elevated leukocyte count
o May be caused by recent infection or stress
– Differential count: measures amount of each type of
leukocyte and whether any are immature
o Useful for clinical diagnoses
62
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18.3c Leukocytes
• Differential count and changes in leukocyte profiles
(continued)
– Neutrophilia: increase in neutrophils
o Associated with bacterial infections, stress, tissue necrosis
o Left-shifted differential: immature neutrophils enter circulation
– Named for the way lab results were printed
– Neutropenia: decreased neutrophil count
o May occur with anemia, drug or radiation therapies
63
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18.3c Leukocytes
• Differential count and changes in leukocyte profiles
(continued)
– Lymphocytosis: increase in lymphocytes
o Caused by viral infections (e.g., mumps, mononucleosis)
o Also caused by chronic bacterial infections, some leukemias, and
multiple myeloma
– Decreases in lymphocyte count occur with HIV, other
leukemias, and sepsis
– Eosinophil numbers rise during allergic reactions, parasitic
infections, and some autoimmune diseases
64
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18.3c Leukocytes
• Differential count and changes in leukocyte profiles
(continued)
– Monocyte count changes
o Increases in response to chronic inflammatory disorders or tuberculosis
o Decreases in response to prolonged prednisone therapy
– Basophil count changes
o Increases in response to myeloproliferative disorders (overproduction
in bone marrow)
– Decreases in response to acute allergic and stress reactions
65
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Clinical View: Leukemia
• Malignancy in leukocyte-forming cells
• Abnormal development and proliferation of leukocytes
– Increase in abnormal leukocyte number
– Decrease in erythrocyte and megakaryocytic lines
• Results in anemia and bleeding
• Acute leukemia
– Rapid progression
– Death typically within months in children and young adults
• Chronic leukemia
– Slower progression
– In middle-aged and older individuals
66
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18.3d Platelets
• Platelets (thrombocytes)
– Small, membrane-enclosed cell fragments
o No nucleus
o Break off of megakaryocytes in red marrow
– Important role in blood clotting
– Normally 150,000 to 400,000 per cubic millimeter blood
o 30% stored in spleen
– Circulate for 8 to 10 days; then broken down and recycled
67
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•
What did you
learn?
•
•
•
•
•
Where does hemopoiesis occur?
How does a reticulocyte differ
from a fully mature erythrocyte?
How might an endurance athlete
benefit from training at high
altitude?
What causes lymphocytosis?
Which type of leukocyte
decreases histamine release
when someone takes an
antihistamine?
What types of antibodies are
found in the plasma of someone
with Type B blood?
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68
1.
18.4
Hemostasis
2.
3.
Learning
Objectives:
4.
5.
6.
7.
Describe vascular spasm, the first phase
of hemostasis.
Name conditions that bring about
vascular spasm.
Describe what happens when platelets
encounter damage in a blood vessel.
Compare and contrast the intrinsic
pathway and the extrinsic pathway for
activating blood clotting.
Describe events in the common
pathway.
Discuss the survival response that
occurs when blood loss exceeds 10%.
Explain the processes of clot retraction
and fibrinolysis.
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69
Hemostasis
• Hemostasis: stoppage of bleeding
– Three overlapping phases
o Vascular spasm
o Platelet plug formation
o Coagulation phase
70
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Hemostasis
Figure 18.12
71
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18.4a Vascular Spasm
• Vascular spasm: blood vessel constriction
– First phase in response to blood vessel injury
– Limits blood leakage
– Lasts from few to many minutes
o Platelets and endothelial cells release chemicals that stimulate
further constriction
– Greater vasoconstriction with greater vessel damage
72
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18.4b Platelet Plug Formation
• Normally (when uninjured) platelet activation is inhibited
– Vessel’s endothelial wall smooth and coated with prostacyclin
o Prostacyclin is an eicosanoid that repels platelets
– It causes endothelial cells and platelets to make cAMP which inhibits
platelet activation
• When blood vessel damaged, a platelet plug is formed
–
–
–
–
Collagen fibers in vessel wall exposed
Platelets stick to collagen with help of von Willebrand factor
Platelets develop long processes allowing for better adhesion
Many platelets aggregate and close off injury
73
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18.4b Platelet Plug Formation
• Platelet activation
– Platelets’ cytosol degranulates and releases chemicals
o Serotonin and thromboxane A2 cause prolonged vascular spasms
o Adenosine diphosphate (ADP) and thromboxane A2 attract other
platelets and facilitate their degranulation (positive feedback)
o Procoagulants stimulate coagulation
o Mitosis stimulating substances trigger repair of blood vessel
– Thrombocytopenia (low platelet count) impairs all phases of
hemostasis
– Platelet plug forms quickly (1 min) but is prevented from getting
too large by prostacyclin secretion by nearby, healthy cells
74
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18.4c Coagulation Phase
• Coagulation: blood clotting
– Network of fibrin (insoluble protein) forms a mesh
o Fibrin comes from soluble precursor fibrinogen
– Mesh traps erythrocytes, leukocytes, platelets, plasma
proteins to form clot
Figure 18.11
75
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18.4c Coagulation Phase
• Substances involved in coagulation
– Clotting requires calcium, clotting factors, platelets, vitamin K
– Clotting factors—most are inactive enzymes
o Named in order of their discovery
– Factor 1= fibrinogen; factor II = prothrombin etc.
o Most are produced in the liver
– Vitamin K
o A fat-soluble coenzyme required for synthesis of clotting factors II, VII,
IX, X
– Some factors (e.g., factor VII) are proteases that cleave other
factors from inactive to active forms
76
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18.4c Coagulation Phase
• Initiation of coagulation cascade
– Clotting starts with the intrinsic and extrinsic pathways
o The paths converge to one common pathway
– Intrinsic (contact activation) pathway
o Initiated by platelets upon damage to inside of vessel wall
o Five steps that are complete in 3 to 6 minutes:
1)
2)
3)
4)
Platelets adhering to vessel wall release factor XII.
Factor XII converts inactive factor XI to active factor XI.
Factor XI changes inactive factor IX to active factor IX.
Factor IX binds with Ca2+ and platelet factor 3 to form a complex.
It converts inactive factor VIII to active factor VIII.
5) Factor VIII changes inactive factor X to active factor X.
77
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18.4c Coagulation Phase
• Initiation of coagulation cascade (continued)
– Extrinsic (tissue factor) pathway
o Initiated by damage outside of vessel
o Two steps take about 15 seconds
1) Tissue thromboplastin released from damaged tissues combines with
factor VII and Ca2+ to form a complex.
2) This complex converts inactive factor X to active factor X.
78
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18.4c Coagulation Phase
• Initiation of coagulation cascade (continued)
– Common pathway
o Activated by extrinsic or intrinsic pathway
o Four steps
1) Factor X combines with factors II and V, Ca2+ , and platelet factor 3 to
form prothrombin activator.
2) Prothrombin activator activates prothrombin to thrombin.
3) Thrombin converts soluble fibrinogen to soluble fibrin.
4) Factor XIII is activated in presence of Ca2+.
Factor XIII cross-links fibrin monomers into a fibrin polymer.
– Positive feedback leads to clot formation
– Clot stops once fibrin fills mesh
o Extra fibrin is destroyed by enzymes in the blood
79
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Coagulation
Pathways
Figure 18.13
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18.4c Coagulation Phase
• The sympathetic response to blood loss
– If greater than 10% of blood lost
o Sympathetic nervous system increases vasoconstriction, heart rate,
force of heart contraction
o Blood redistributed to heart and brain
o Effective in maintaining blood pressure until 40% of blood lost
81
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18.4d Elimination of the Clot
• Clot elimination includes clot retraction and fibrinolysis
– Clot retraction
o Actinomyosin (protein within platelets) contracts and squeezes serum
out of developing clot making it smaller
– Fibrinolysis
o Degradation of fibrin strands by plasmin
o Begins within 2 days after clot formation
o Occurs slowly over a number of days
82
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18.4d Elimination of the Clot
• Blood balances clot elimination and clot formation
– Imbalances can lead to bleeding or blood clotting disorders
– Damaged vessels, impaired blood flow, atherosclerosis or
vessel inflammation tip the balance toward clotting
o Certain nutrients, ions, vitamins must be present for clot to form
correctly
83
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Clinical View: Bleeding and Blood Clotting Disorders
• Hemophilias: bleeding disorders
– Hemophilia A and hemophilia B most common
o Occur in X-linked recessive pattern
o Males exhibit full-blown disease; females typically carriers
o Result from deficiency of factor VIII, factor IX, or factor XI (more rare)
• Thrombocytopenia: platelet deficiency
– Increased breakdown or decreased production
– May occur in bone marrow infections or cancer
• Certain drugs interfere with clotting (can cause bleeding)
– E.g., aspirin, ibuprofen, warfarin, ginkgo
84
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Clinical View: Bleeding and Blood Clotting Disorders
(continued)
• Hypercoagulation
–
–
–
–
Increased tendency to clot blood
Can lead to thrombus, blood vessel clot
When dislodged within blood, embolus
If lodges in lungs, pulmonary embolism
o Can cause breathing problems and death
– Can have drug-related, environmental, and genetic causes
o E.g., birth control pills, prolonged inactivity
85
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What did you
learn?
•
What role does fibrin play in
clot formation?
•
What is the first step in the
intrinsic pathway of the
coagulation cascade?
•
What autonomic nervous
system responses occur during
blood loss?
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86
18.5
Development
and Aging
of Blood
Learning
Objectives:
1.
Describe when and how blood is
formed in the embryo, fetus,
childhood, and adulthood.
2.
List some conditions that occur
with the bone marrow and blood in
the elderly.
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87
18.5 Development and Aging of Blood
• Stages of blood development
– First hemopoietic stem cells develop in embryonic yolk sac
wall
o Go on to colonize liver, spleen, thymus
– These cells become hemocytoblasts
• Colonize red bone marrow
• By birth, all production here
– Hemopoiesis
• Occurs in most bones in young children
• Restricted to selected bones in axial skeleton in adulthood
88
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18.5 Development and Aging of Blood
• Aging and blood
–
–
–
–
Older red bone marrow replaced with fat as individuals age
Older individuals more likely to become anemic
May produce fewer and less active leukocytes
Certain types of leukemia more prevalent in elderly
89
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What did you
learn?
•
Where does hemopoiesis
occur in children?
•
How does bone marrow
change in the elderly?
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90