Transcript Blood, a more in-depth examination

Blood, a more in-depth
examination
Section 1: Blood
• Functions of blood
– Transportation of dissolved gases, nutrients,
hormones, and metabolic wastes
– Regulation of the pH and ion composition of
interstitial fluids
– Restriction of fluid loss at injury sites
– Defense against toxins and pathogens
– Stabilization of body temperature
Module 17.1: Blood components
• Blood
– Is a fluid connective tissue
– About 5 liters (5.3 quarts) in body
• 5–6 in males, 4–5 in females (difference mainly body size)
– Consists of:
• Plasma (liquid matrix)
• Formed elements (cells and cell fragments)
– Properties
• Temp is roughly 38°C (100.4°F)
• Is 5× more viscous than water (due to solid components)
• Is slightly alkaline (average pH 7.4)
Module 17.1: Blood components
• Whole blood
– Term for removed blood when composition is
unaltered
• May be fractionated or separated
– Plasma
» 46%–63% of blood volume
– Hematocrit (or packed cell volume [PCV])
» Percentage of whole blood contributed by formed elements
(99% of which are red blood cells)
» Average 47% for male (range 40%–54%)
» Average 42% for female (range 37%–47%)
Module 17.1: Blood components
• Plasma
– Composition resembles interstitial fluid in many ways
•
•
•
•
Exists because exchange of water, ions, and small solutes
92% water
7% plasma proteins
1% other solutes
– Primary differences
• Levels of respiratory gases (oxygen and carbon dioxide)
• Concentrations of dissolved proteins (cannot cross capillary
walls)
Module 17.1: Blood components
• Plasma proteins
– In solution rather than as fibers like other
connective tissues
– Each 100 mL has ~7.6 g of protein
• ~5× that of interstitial fluid
– Large size and globular shapes prevent leaving
bloodstream
– Liver synthesizes >90% of all plasma proteins
Module 17.1: Blood components
• Plasma proteins (continued)
– Albumins
• ~60% of all plasma proteins
• Major contributors to plasma osmotic pressure
– Globulins
• ~35% of all plasma proteins
• Antibodies (immunoglobulins) that attack pathogens
• Transport globulins that bind ions, hormones, compounds
– Fibrinogen
• Functions in clotting and activate to form fibrin strands
– Many active and inactive enzymes and hormones
Module 17.1: Blood components
• Plasma solutes
– Electrolytes
• Essential for vital cellular activities
• Major ions are Na+, K+, Ca2+, Mg2+, Cl–, HCO3–, HPO4–, SO42–
– Organic nutrients
• Used for cell ATP production, growth, and maintenance
• Includes lipids, carbohydrates, and amino acids
– Organic wastes
• Carried to sites of breakdown or excretion
• Examples: urea, uric acid, creatinine, bilirubin, NH4+
Plasma
(46–63%)
Whole
blood
consists of
Formed
elements
(37–54%)
Figure 17.1
1
Module 17.1: Blood components
• Formed elements
– Platelets
• Small membrane-bound cell fragments involved in clotting
– White blood cells (WBCs)
• Also known as leukocytes (leukos, white + -cyte, cell)
• Participate in body’s defense mechanisms
• Five classes, each with different functions
– Red blood cells (RBCs)
• Also known as erythrocytes (erythros, red + -cyte, cell)
• Essential for oxygen transport in blood
Module 17.1 Review
a. Define hematocrit.
b. Identify the two components constituting
whole blood, and list the composition of
each.
c. Which specific plasma proteins would you
expect to be elevated during an infection?
Module 17.2: Red blood cells
• RBCs in blood
– Most numerous cell type in blood
•
Roughly 1/3 of all cells in the body
– Red blood cell count (standard blood test) results
•
•
•
Adult males: 4.5–6.3 million RBCs/1 µL or 1 mm3 of whole
blood
Adult females: 4.2–5.5 million RBCs/1 µL or 1 mm3 of
whole blood
One drop = 260 million RBCs
Module 17.2: Red blood cells
• RBC characteristics
– Biconcave disc
– Average diameter ~8 µm
– Large surface area-to-volume ratio
•
Greater exchange rate of oxygen
– Can form stacks (rouleaux)
•
Facilitate smooth transport through small vessels
– Are flexible
•
Allow movement through capillaries with diameters
smaller than RBC (as narrow as 4 µm)
Stained blood smear
LM x 450
Figure 17.2
1
The size and biconcave shape of an RBC
7.2–8.4 μm
0.45–1.16 μm
RBCs
2.31–2.85 μm
Colorized SEM x 1800
Figure 17.2
2
The advantages of the biconcave shape of RBCs
Functional Aspects of Red Blood Cells
• Large surface area-to-volume ration. Each
RBC carries oxygen bound to intracellular
proteins, and that oxygen must be absorbed or
released quickly as the RBC passes through the
capillaries. The greater the surface area per unit
volume, the faster the exchange between the
RBC’s interior and the surrounding plasma. The
total surface area of all the RBCs in the blood of a
typical adult is about 3800 square meters, roughly
2000 times the total surface area of the body.
Rouleaux
(stacks of RBCs)
Blood vessels (viewed
in longitudinal section)
• RBCs can form stacks. Like dinner plates,
RBCs can form stacks that ease the flow through
narrow blood vessels. An entire stack can pass
along a blood vessel only slightly larger than the
diameter of a single RBC, whereas individual
cells would bump the walls, bang together, and
form logjams that could restrict or prevent blood
flow.
• Flexibility. Red blood cells are very flexible and
can bend and flex when entering small capillaries
and branches. By changing shape, individual
RBCs can squeeze through capillaries as narrow
as 4 μm.
Nucleus of endothelial cell
Red blood cell (RBC)
Sectional view of capillaries
LM x 1430
Figure 17.2
3
Module 17.2: Red blood cells
•
RBC characteristics (continued)
–
Lose most organelles including nucleus during development
•
–
Cannot repair themselves and die in ~120 days
Contain many molecules (hemoglobin) associated with
primary function of carrying oxygen
•
•
Each cell contains ~280 million hemoglobin (Hb) molecules
Normal whole blood content (grams per deciliter)
–
•
14–18 dL (males), 12–16 dL (females)
~98.5% of blood oxygen attached to Hb in RBCs
–
Rest of oxygen dissolved in plasma
Module 17.2: Red blood cells
•
Hemoglobin
–
–
Protein with complex quaternary structure
Each molecule has 4 chains (globular protein subunits)
•
•
–
2 alpha (α) chains
2 beta (β) chains
Each chain contains a single heme pigment molecule
•
Each heme (with iron) can reversibly bind one molecule of oxygen
–
Forms oxyhemoglobin (HbO2) (bright red)
»
Deoxyhemoglobin when not binding O2 (dark red)
Figure 17.2
4
The quaternary structure
of hemoglobin
β chain 1
α chain 1
β chain 2
Heme
α chain 2
Figure 17.2
5
The chemical structure
of a heme unit
Heme
Figure 17.2
6
Module 17.2 Review
a. Define rouleaux.
b. Describe hemoglobin.
c. Compare oxyhemoglobin with
deoxyhemoglobin.
Module 17.3: Red blood cell
production and recycling
• RBC production and recycling
– Events occurring in red bone marrow
• Blood cell formation (erythropoiesis) occurs only in red
bone marrow (myeloid tissue)
– Located in vertebrae, ribs, sternum, skull, scapulae, pelvis, and
proximal limb bones
• Fatty yellow bone marrow can convert to red bone
marrow in cases of severe, sustained blood loss
• Developing RBCs absorb amino acids and iron from
bloodstream and synthesize Hb
Module 17.3: Red blood cell
production and recycling
• Events occurring in red bone marrow (continued)
– Stages
• Proerythroblasts
• Erythroblasts
– Actively producing Hb
– After four days becomes normoblast
• Reticulocyte (80% of mature cell Hb)
– Ejects organelles including nucleus
– Enters bloodstream after two days
– After 24 hours in circulation, is mature RBC
Module 17.3: Red blood cell
production and recycling
• Events occurring at macrophages
– Engulf old RBCs before they rupture (hemolyze)
– Hemoglobin recycling
• Iron
– Stored in phagocyte
– Released into bloodstream attached to plasma protein (transferrin)
• Globular proteins disassembled into amino acids for other uses
• Heme  biliverdin  bilirubin  bloodstream
• Hemoglobin not phagocytized breaks down into protein chains and
eliminated in urine (hemoglobinuria)
Module 17.3: Red blood cell
production and recycling
• Events occurring at liver
– Bilirubin excreted into bile
• Accumulating bile due to diseases or disorders can
lead to yellowish discoloration of eyes and skin
(jaundice)
• Events occurring at the large intestine
– Bacteria convert bilirubin to urobilins and
stercobilins which become part of feces
• Give feces yellow-brown or brown coloration
Module 17.3: Red blood cell
production and recycling
• Events occurring at kidneys
– Excrete some hemoglobin and urobilins
• Give urine its yellow color
– Presence of intact RBCs in urine (hematuria)
• Only after urinary tract damage
Events Occurring in the Red Bone Marrow
Start
Developing RBCs absorb amino
acids and Fe2+ from the bloodstream
and synthesize new Hb molecules.
Proerythroblasts then differentiate
into various stages of cells called
erythroblasts, which actively
synthesize hemoglobin.
Erythroblasts are named
according to total size, amount of
hemoglobin present, and size and
appearance of the nucleus.
Events in the life cycle of RBCs
Events Occurring in
Macrophages
Macrophages in liver,
spleen, and bone marrow
Fe2+
Heme
Fe2+ transported in circulation
RBC
formation
by transferrin
Amino acids
Average life span of
RBC is 120 days
90%
Biliverdin
Bilirubin
10%
Bilirubin bound
to albumin in
bloodstream
Cells destines to become RBCs first
differentiate into proerythroblasts.
Old and
damaged
RBCs
In the bloodstream,
the rupture of RBCs
is called hemolysis.
Hemoglobin that is not phagocytized
breaks down, and the alpha and beta
chains are eliminated in urine. When
abnormally large numbers of RBCs
break down in the bloodstream, urine
may turn red or brown. This condition
is called hemoglobobinuria.
Ejection of
nucleus
After roughly four days of differentiation, the
erythroblast, now called a normoblast, sheds
its nucleus and becomes a reticulocyte
(re-TIK-ū-lō-sīt), which contains 80 percent of
the Hb of mature RBC.
After two days in the bone marrow,
reticulocytes enter the bloodstream. After 24
hours in circulation, the reticulocytes
complete their maturation and become
indistinguishable from other mature RBCs.
New RBCs
released into
circulation
Liver
Bilirubin
Events Occurring in the Kidney
Absorbed into the circulation
Excreted
in bile
Hb
Events Occurring in
the Liver
Bilirubin
Urobilins
Urobilins,
sterconilins
Events Occurring in the Large Intestine
Eliminated
in feces
Eliminated
in urine
Figure 17.3
Module 17.3 Review
a. Define hemolysis.
b. Identify the products formed during the
breakdown of heme.
c. In what way would a liver disease affect the
level of bilirubin in the blood?
Module 17.4: Blood types
• Blood types
– Determined by presence or absence of cell surface
markers (antigens)
•
•
•
•
Are genetically determined glycoproteins or glycolipids
Can trigger a protective defense mechanism (immune
response)
Identify blood cells as “self” or “foreign” to immune
system
More than 50 blood cell surface antigens exist
–
Three particularly important
» A, B, Rh (or D)
Module 17.4: Blood types
• Four blood types (AB antigens)
1. Type A (A surface antigens)
•
Anti-B antibodies in plasma
2. Type B (B surface antigens)
•
Anti-A antibodies in plasma
3. Type AB (Both A and B surface antigens)
•
No anti-A or anti-B antibodies in plasma
4. Type O (no A or B surface antigens)
•
Both anti-A and anti-B antibodies in plasma
The characteristics of blood for each of the four blood types
Type A
Type B
Type A blood has RBCs
with surface antigen A only.
Type B blood has RBCs
with surface antigen B only.
Surface
antigen A
Surface
antigen B
If you have Type A blood,
your plasma contains anti-B
antibodies, which will attack
Type B surface antigens.
If you have Type B blood,
your plasma contains anti-A
antibodies.
Type AB
Type O
Type AB blood has RBCs
with both A and B surface
antigens.
Type O blood has RBCs
lacking both A and B
surface antigens.
If you have Type AB blood,
your plasma has neither
anti-A nor anti-B antibodies.
If you have Type O blood,
your plasma contains both
anti-A and anti-B antibodies.
Figure 17.4
1
Module 17.4: Blood types
• Rh surface antigens
– Separate antigen from A or B
– Presence or absence on RBC determines
positive or negative blood type respectively
– Examples: AB+, O–
Figure 17.4
3
Module 17.4: Blood types
•
Antigen-antibody interactions
–
Antibodies “protect our bodies” from “foreign” blood cells
•
–
Anti-A and anti-B antibodies remain constant through life while antiRh antibodies can develop for Rh– people
If one blood type is exposed to corresponding antibodies,
clumping (agglutination) occurs
•
•
Hemolysis may occur
Cross-reactions (transfusion reactions) can block blood vessels to
vital organs with agglutinated RBCs or cell fragments
–
Important to make sure donor and recipient blood types are
compatible (will not cross-react)
The events in a cross-reaction between incompatible donor and recipient blood types
RBC
Surface antigens
Opposing antibodies
Agglutination (clumping)
Hemolysis
Figure 17.4
2
Results of blood typing tests on blood samples from four individuals
Anti-A
Anti-B
Anti-D
Blood
type
A+
B+
AB+
O–
Figure 17.4
4
Module 17.4 Review
a. What is the function of surface antigens on
RBCs?
b. Which blood type(s) can be safely
transfused into a person with Type O
blood?
c. Why can’t a person with Type A blood safely
receive blood from a person with Type B
blood?
CLINICAL MODULE 17.5: Newborn
hemolytic disease
• Newborn hemolytic disease
– Genetically determined antigens mean that a
child can have a blood type different from either
parent
– During pregnancy, the placenta restricts direct
transport between maternal and infant blood
•
•
Anti-A and anti-B antibodies are too large to cross
Anti-Rh antibodies can cross
– Can lead to mother’s antibodies attacking fetal RBCs
CLINICAL MODULE 17.5: Newborn
hemolytic disease
• First pregnancy with Rh– mother and Rh+ infant
– During pregnancy, few issues occur because no
anti-Rh antibodies exist in maternal circulation
– During birth, hemorraging may expose maternal
blood to fetal Rh+ cells
•
Leads to sensitization or activation of mother’s immune
system to produce anti-Rh antibodies
Rh–
mother
First Pregnancy of an Rh– Mother
with an Rh+ infant
Rh+
fetus
The most common form of hemolytic disease of
the newborn develops after an Rh– women has
carried an Rh+ fetus.
During First Pregnancy
Problems seldom develop during a
first pregnancy, because very few fetal
cells enter the maternal circulation
then, and thus the mother’s immune
system is not stimulated to produce
anti-Rh antibodies.
Maternal blood supply
and tissue
Placenta
Fetal blood supply
and tissue
Exposure to fetal red blood cell
antigens generally occurs during
delivery, when bleeding takes place at
the placenta and uterus. Such mixing
of fetal and maternal blood can
stimulate the mother’s immune system
to produce anti-Rh antibodies, leading
to sensitization.
Hemorrhaging at Delivery
Maternal blood supply
and tissue
Fetal blood supply
and tissue
Roughly 20 percent of Rh– mothers
who carried Rh+ children become
sensitized within 6 months of delivery.
Because the anti-Rh antibodies are not
produced in significant amounts until
after delivery, a woman’s first infant is
not affected.
Rh antigen on
fetal red blood cells
Maternal Antibody Production
Maternal blood supply
and tissue
Maternal antibodies
to Rh antigen
Figure 17.5
•
CLINICAL MODULE 17.5: Newborn
hemolytic disease
Second pregnancy with Rh– mother and Rh+ infant
–
Subsequent pregnancy with Rh+ infant can allow maternal anti-Rh
antibodies to cross placental barrier
•
Attack fetal RBCs and cause hemolysis and anemia
–
–
= Erythroblastosis fetalis
Full transfusion of fetal blood may be necessary to remove maternal
anti-Rh antibodies
Prevention
–
•
RhoGAM antibodies can be administered to maternal circulation at 26–
28 weeks and before/after birth
–
–
Destroys any fetal RBCs that cross placenta
Prevents maternal sensitization
Rh–
mother
Second Pregnancy of an Rh– Mother
with an Rh+ Infant
If a subsequent pregnancy involves an Rh+ fetus,
maternal anti-Rh antibodies produced after the
first delivery cross the placenta and enter the
fetal bloodstream. These antibodies destroy
fetal RBCs, producing a dangerous anemia.
The fetal demand for blood cells increases,
and they begin leaving the bone marrow and
entering the bloodstream before completing
their development. Because these immature
RBCs are erythroblasts, HDN is also known
as erythroblastosis fetalis. Fortunately, the
mother’s anti-Rh antibody production can
be prevented if such antibodies (available
under the name RhoGAM) are administered
to the mother in weeks 26–28 of pregnancy
and during and after delivery. These
antibodies destroy any fetal RBCs that
cross the placenta before they can stimulate
a maternal immune response. Because
maternal sensitization does not occur, no
anti-Rh antibodies are produced.
Rh+
fetus
During Second Pregnancy
Maternal blood supply
and tissue
Maternal anti-Rh
antibodies
Fetal blood supply
and tissue
Hemolysis of
fetal RBCs
Figure 17.5
CLINICAL MODULE 17.5 Review
a. Define hemolytic disease of the newborn
(HDN).
b. Why is RhoGAM administered to Rh–
mothers?
c. Does an Rh+ mother carrying an Rh– fetus
require a RhoGAM injection? Explain your
answer.
Module 17.6: White blood cells
• White blood cells (leukocytes)
– Spend only a short time in circulation
• Mostly located in loose and dense connective tissues
where infections often occur
• Can migrate out of bloodstream
– Contact and adhere to vessel walls near infection site
– Squeeze between adjacent endothelial cells
– = Emigration or diapedesis
• Are attracted to chemicals from pathogens, damaged
tissues, or other WBCs
– = Positive chemotaxis
Module 17.6: White blood cells
• White blood cell types
1. Granular leukocytes (have cytoplasmic granules)
•
•
•
Neutrophil
Eosinophil
Basophil
2. Agranular leukocytes (lacking cytoplasmic granules)
•
•
Monocyte
Lymphocyte
• Changing populations of different WBC types associated with
different conditions can be seen in a differential WBC count
Module 17.6: White blood cells
• Granular leukocytes
– Neutrophils
• Multilobed nucleus
• Phagocytic cells that engulf pathogens and debris
– Eosinophils
• Granules generally stain bright red
• Phagocytic cells that engulf antibody-labeled materials
– Increase abundance with allergies and parasitic infections
– Basophils
• Granules generally stain blue
• Release histamine and other chemicals promoting inflammation
The structure and function of white
blood cells (leukocytes)
GRANULAR LEUKOCYTES
Neutrophil
Eosinophil
Basophil
WBCs can be
divided into
two classes
Shared Properties of WBCs
• WBCs circulate for only a short portion of their
life span, using the bloodstream primarily to
travel between organs and to rapidly reach
areas of infection or injury. White blood cells
spend most of their time migrating through
loose and dense connective tissues throughout
the body.
AGRANULAR LEUKOCYTES
Monocyte
Lymphocyte
• All WBCs can migrate out of the bloodstream.
When circulating white blood cells in the
bloodstream become activated, they contact
and adhere to the vessel walls and squeeze
between adjacent endothelial cells to enter the
surrounding tissue. This process is called
emigration, or diapedesis (dia, through;
pedesis, a leaping).
• All WBCs are attracted to specific chemical
stimuli. This characteristic, called postive
chemotaxis (kē-mō-TAK-sis), guides WBCs to
invading pathogens, damaged tissues, and
other active WBCs.
• Neutrophils, eosinophils, and monocytes are
capable of phagocytosis. These phagocytes can
engulf pathogens, cell debris, or other
materials. Macrophages are monocytes that
have moved out of the bloodstream and have
become actively phagocytic.
Figure 17.6
Module 17.6: White blood cells
• Agranular leukocytes
– Monocytes
• Large cells with bean-shaped nucleus
• Enter tissues and become macrophages (phagocytes)
– Lymphocytes
• Slightly larger than RBC with large round nucleus
• Provide defense against specific pathogens or toxins
Module 17.6 Review
a. Identify the five types of white blood cells.
b. Which type of white blood cell would you find
in the greatest numbers in an infected cut?
c. How do basophils respond during
inflammation?
Module 17.7: Formed element
production
• Formed elements
– Appropriate term since platelets are cell
fragments
•
Platelets
–
–
–
Structure: flattened discs that appear round when viewed
from top but spindle-shaped in blood smear
Function: clump together and stick to damaged vessel
walls where they release clotting chemicals
Immediate precursor cell is megakaryocyte (mega-, big +
karyon, nucleus + -cyte, cell)
Figure 17.7
2
•
Module 17.7: Formed element
production
Formed element production
–
–
All formed elements are produced in adult red bone marrow
All cells arise from multipotent stem cells
•
•
= Hemocytoblasts (hemo-, blood + cyto, + blastos, precursor)
Give rise to two other stem cell lines
1.
2.
Lymphoid stem cells (produce lymphocytes)
»
Occur in red marrow and lymphoid tissues
Myeloid stem cells (produce other formed elements)
Animation: Formed Elements
The early stages in the
development of formed
elements, which occurs
in the highly vascular red
marrow of adult bones
Figure 17.7
1
The early stages in the development of
formed elements, which occurs in the
highly vascular red marrow of adult bones
Nutrient
artery
Venous
sinuses
Red bone
marrow
Figure 17.7
1
The early stages in the development of formed elements,
which occurs in the highly vascular red marrow of adult bones
Lymphoid Stem Cells
Hemocytoblasts
Hemocytoblasts
(hemo-, blood + cyte,
cell + blastos,
precursor), or
multipotent stem
cells, are found in
the red bone
marrow of adults.
Their divisions give
rise to two types of
stem cells responsible
for producing all
formed elements.
Lymphoid stem
cells, which are
responsible for the
production
of lymphocytes,
originate in the red
bone marrow. Some
remain there, while
others migrate from the
bone marrow to other
lymphoid tissues,
including the thymus,
spleen, and lymph
nodes. As a result,
lymphocytes are
produced in these
organs as well as in the
red bone marrow.
Myeloid Stem Cells
Myeloid Stem Cells
are stem cells in red
bone marrow that
divide to give rise
to all types of
formed elements
other than
lymphocytes.
Figure 17.7
1
Module 17.7: Formed element
production
• Erythropoietin (EPO)
– Released into plasma when peripheral tissues
(especially kidneys) have low oxygen (hypoxia)
•
Examples
1.
2.
3.
4.
During anemia
When kidney blood flow declines
When oxygen content of air in lungs declines due to disease or
altitude
When respiratory surfaces are damaged
– Transported to red bone marrow and stimulates
stem cells and developing RBCs
Module 17.7 Review
a. Define hemocytoblast.
b. Explain the role of erythropoietin.
c. Compare lymphoid stem cells with myeloid
stem cells.
Module 17.8: Hemostasis
• Hemostasis (haima, blood + stasis, halt)
– Stops blood loss from damaged blood vessel
walls
– Establishes framework for tissue repairs
– Usually divided into three phases but
continuous process
1. Vascular phase
2. Platelet phase
3. Coagulation phase
Module 17.8: Hemostasis
1. Events of the vascular phase
–
Endothelial cells contract exposing underlying basal lamina
to bloodstream
Endothelial cells release chemical factors, local hormones,
and endothelins
–
•
Endothelin functions
1.
2.
–
Stimulate smooth muscle and vascular spasms
Stimulate division of endothelial cells, smooth muscle cells, and
fibroblasts
Endothelial cells become sticky
•
•
In capillaries, cells can reduce flow in vessel
Can cause platelets to attach
The vascular phase of hemostasis
Vascular Phase
Lasts for roughly 30 minutes after the injury occurs;
is dominated by the response of the endothelial
cells and the smooth muscle of vessel walls
Knife blade
Blood vessel injury
Vascular spasm
Events of the Vascular Phase
• The endothelial cells contract and expose the
underlying basal lamina to the bloodstream.
• The endothelial cells begin releasing chemical
factors and local hormones. Endothelial cells also
release endothelins, peptide hormones that (1)
stimulate smooth muscle contraction and promote
vascular spasms and (2) stimulate the division of
endothelial cells, smooth muscle cells, and
fibroblasts to accelerate the repair process.
• The endothelial plasma membranes become
“sticky”. A tear in the wall of a small artery or vein
may be partially sealed off by the attachment of
endothelial cells on either side of the break. In
small capillaries, endothelial cells on opposite
sides of the vessel may stick together and prevent
blood flow along the damaged vessel. The
stickiness also facilitates the attachment of
platelets as the platelet phase gets under way.
Figure 17.8
1
Module 17.8: Hemostasis
2. Events of the platelet phase
–
Begins with platelet attachment to endothelial cells, basal lamina,
exposed collagen fibers, and each other
Platelets release chemicals
–
•
•
•
•
•
ADP (stimulates platelet aggregation and secretion)
Chemicals that stimulate vascular spasm
Platelet factors (proteins play role in clotting)
Platelet-derived growth factor (PDGF) (promotes vessel repair)
Calcium ions (required for platelet aggregation and clotting process)
The platelet phase of hemostasis
Platelet Phase
Begins with the attachment of platelets to sticky endothelial
surfaces, to the basal lamina, to exposed collagen fibers, and to
each other
Plasma in
vessel lumen
Release of chemicals
(ADP, PDGF, Ca2+,
platelet factors)
Platelet
aggregation
Endothelium
Platelet
adhesion to
damaged
vessel
Basal
lamina
Vessel
wall
Platelet plug
may form
Interstitial
fluid
Contracted smooth
muscle cells
Cut edge of
vessel wall
Chemicals Released by Activated Platelets
• Adenosine diphosphate (ADP), which stimulates
platelet aggregation and secretion
• Several chemicals that stimulate vascular spasms
• Platelet factors, proteins that play a role in
blood clotting
• Platelet-derived growth factor (PDGF), a
peptide that promotes vessel repair
• Calcium ions, which are required for platelet
aggregation and in several steps in the clotting
process
Figure 17.8
2
Module 17.8: Hemostasis
3. Events of coagulation phase
•
•
Starts 30 seconds or more after damage
Involves complex sequence of steps leading to
conversion of circulating fibrinogen to insoluble fibrin
–
•
Procoagulants (clotting factors) play a key role
–
–
•
Blood cells and platelets are trapped in fibrin network
Many are enzymes essential to clotting response
Activated enzymes lead to chain reaction (cascade)
Two pathways that both lead to common pathway
–
Extrinsic and Intrinsic
Module 17.8: Hemostasis
3. Events of coagulation phase (continued)
•
Extrinsic pathway
–
–
Begins with release of tissue factor (Factor III) from
endothelial cells or peripheral tissues
Tissue factor combines with Ca2+ and another clotting
factor to activate Factor X (first step in common pathway)
Module 17.8: Hemostasis
3. Events of coagulation phase (continued)
•
Intrinsic pathway
–
–
–
Begins with proenzymes exposed to collagen fibers at
injury site
Pathway proceeds with assistance of PF-3 (factor released
by aggregating platelets)
Sequence of enzyme activations leads to Factor X
Module 17.8: Hemostasis
3. Events of coagulation phase (continued)
•
Common Pathway
–
–
Activated Factor X forms prothrombinase
» An enzyme that converts proenzyme prothrombin to the
enzyme thrombin
Thrombin converts fibrinogen to fibrin
» Completes clotting process
• Clot retraction
– RBCs and platelets stick to clot
•
Platelets contract to form tighter clot
Module 17.8: Hemostasis
• Events of dissolving clots (fibrinolysis) after
tissue repair
– Proenzyme plasminogen is activated by
•
•
Thrombin in common pathway
Tissue plasminogen activator (t-PA) released by
damaged tissues
– Plasminogen becomes plasmin which erodes
clot
Module 17.8 Review
a. Define hemostasis.
b. Briefly describe the vascular, platelet, and
coagulation phases of hemostasis.
c. Provide the correct sequence for the following
list of events involved in the process of
hemostasis:
1. coagulation; 2. fibrinolysis; 3.
vascular spasm; 4. retraction; 5. platelet phase.
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Blood disorders and diseases
– Venipuncture (vena, vein + punctura, a piercing)
•
•
Withdrawal of whole blood from vein
Commonly used because:
1. Easy to locate superficial veins
2. Vein walls are thinner than comparable arteries
3. Venous blood pressure is relatively low, so seals quickly
•
Most clinical procedures to diagnose many disorders
examine venous blood
•
CLINICAL MODULE 17.9: Blood
disorders and diseases
Nutritional blood disorders
–
Iron deficiency anemia
•
RBCs cannot synthesize functional hemoglobin and are unusually
small (microcytic) because iron reserves or intake is too low
–
–
Women are especially susceptible since their iron reserves are half
that of typical man
Pernicious anemia
•
•
Deficiency of vitamin B12 preventing normal stem cell divisions in
red bone marrow
Few RBCs and often misshapen and large (macrocytic)
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Nutritional blood disorders (continued)
– Clotting disorders
•
Reduced calcium or vitamin K can lead to clotting
disorders since they are involved in many steps of
the clotting process
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Congenital blood disorders
– Sickle cell anemia
•
Sickle-shaped RBCs due to affected amino acid
sequence in Hb beta chains
–
•
Affected cells are fragile and can block vessels
Individuals with disorder must have two copies of
sickling gene
–
Those with one copy have the sickling trait but not
disorder
» Have increased resistance to malaria
•
CLINICAL MODULE 17.9: Blood
disorders and diseases
Congenital blood disorders (continued)
–
Hemophilia
•
•
•
•
Inherited bleeding disorder
Malfunctioning clotting cascade due to reduced production of single
clotting factor
Severity of disorder varies
1 person out of 10,000 affected
–
–
80%–90% males
Thalassemias
•
Diverse group of inherited disorders caused by inability to adequately
produce normal Hb protein subunits
Normal and sickled RBCs
characteristic of the
congenital blood disorder
called sickle cell anemia
Figure 17.9
2
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Infections of the blood
– Pathogens entering the blood through wound or
infection
– Bacteremia
•
Bacteria circulating in blood but not multiplying there
– Viremia
•
Viruses circulating in blood but not multiplying there
– Septicemia
•
Pathogens present and multiplying in blood and
spreading
The legs on an infant with
septicemia (a blood infection)
caused by meningococcal bacteria)
Figure 17.9
2
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Infections of the blood (continued)
– Malaria
•
•
•
Parasitic disease caused by several species of the
protozoan Plasmodium
Kills 1.5–3 million people per year, up to half
children
Initially infects liver but fragments infect RBCs
–
–
Periodically (2–3 days), all RBCs rupture and release more
parasites
Dead RBCs block vessels to vital organs
A mosquito biting a human, and
an RBC infected with the protozoan
parasite Plasmodium, the organism
that causes malaria
Figure 17.9
2
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Tumors of the blood
– Leukemia (cancers of blood-forming tissues)
•
Cancerous cells spread throughout body from their
origin in red bone marrow
–
•
First symptoms appear with presence of immature and
abnormal WBCs in circulation
Two types
1.
2.
Myeloid leukemia (abnormal levels of granulocytes)
Lymphoid leukemia (abnormal levels of lymphocytes and
stem cells)
Abnormal WBCs (marked with
red dots) in a blood smear of an
individual with the cancer called
myeloid leukemia
Figure 17.9
2
CLINICAL MODULE 17.9: Blood
disorders and diseases
• Degenerative blood disorders
– Disseminated intravascular coagulation (DIC)
•
Bacterial toxins activate clotting process steps
–
–
•
Converts too much fibrinogen to fibrin
» Small clots may appear in small vessels
Phagocytes and plasmin work to remove fibrin
Liver works to keep fibrinogen at adequate levels
–
Uncontrolled bleeding may occur without enough fibrinogen
CLINICAL MODULE 17.9 Review
a. Define venipuncture.
b. Identify the two types of leukemia.
c. Compare pernicious anemia with iron
deficiency anemia.