Transcript Presentation 2

Blood
Dr. Robert Anderson
Rowan University
Components of Blood
• Functions
• Distribution of materials to the tissues in the body
•
•
•
•
_________________
_________________
__________________
__________________
• Regulation
•
•
•
•
___________________
___________________
___________________
__________________________
• Protection
• ______________
• __________________
Blood Components
• Plasma – liquid component of blood (55%
of blood volume)
•
•
•
•
•
water
______________
sugar
______________
______________
salts
hormones
______________
Proteins and amino acids
• Formed elements (cells)
Leukocytes
• _______________
– White blood cells (~1% of
blood volume)
Erythrocytes
• _______________
– Red blood cells (~44% of
blood volume)
Thrombocytes – help in forming clots
• ___________
Plasma
• 90% water
• Solutes
•
•
•
•
Proteins – transport proteins (chaperones)
Enzymes
Antibodies
Fibrinogen (forms fibrin to clot blood after
injury)
• The proper chemical balance of plasma
is essential for tissue function!
• Examples?
Metabolites in Plasma
• Cellular Metabolites (Nitrogen containing compounds)
• Urea, uric acid, creatine, ammonia (NH3)
• Electrolytes
Cations
• _________
– Na+, K+, Mg+, Ca+
Anions
• __________
– Cl-, PO4-, SO4-, CO3-
• Respiratory Gases
CO2
• O2
_____,_______
Formed Elements
• Erythrocytes – Red Blood Cells (RBC’s)
•
•
•
•
Biconcave cells
____________
NO Nucleus!
Hemoglobin molecules
Mostly composed of _____________
They do NOT use O2 for respiration (use
Lactic Acid Fermentation instead)
_________________________
• Why are all of these things adaptive??
Hemoglobin
• Quaternary protein molecule made
of two functional parts
• _________
– proteins wound together
Two
(4 total) to hold heme molecule
• _________
– molecule that hold Iron
Heme
atoms (Fe) which have a high affinity
for O2
• How does this relate to the Central
Dogma of Biology?
Sickle Cell Anemia
Sickle Cell anemia
• In ______________________,
globin
proteins are not formed correctly,
making O2 transport difficult
• Low O2 content changes the cell to be
sickle-shaped (no longer biconcave)
• This causes “traffic jams” in the
bloodstream, leading to clots
How can Sickle Cell be Beneficial?
• Mendelian pattern of inheritance (SSA is recessive)
• BB – no allele for SSA
• Bb – carrier for SSA (mildly expressed)
• bb – two alleles for SSA (full phenotype)
B b
B
b
B B
B
b
B B
b
b
Malaria
• Mosquito-borne parasite that enters
and develops in red blood cells
• Over 500 million malaria infections
annually with ~ 5 million deaths
• Malaria trophozoites (feeding stage)
develop in red blood cells
• Cause lysis when emerging from cell
• Cell “sickling” makes blood cells
more resistant to parasite attack!
Anopheles mosquito (vector for Malaria)
Diseases Change our Gene Pool!
Prevalence Map – Sickle Cell
Anemia
Prevalence Map – Malaria
Anemia
Blood hemoglobin
• A decrease in _____________________________________________
• Leads to general fatigue and malaise
• Increased cardiac output
• What factors can cause anemia?
Poor diet
1. __________________
Globin mutation (ineffective
protein)
2. _________________________
Injury
hemorrhage
3. _____________/____________
Leukocytes
• Specifically engage different invaders of the body
(pathogen types)
• Divided into granulocytes and agranulocytes due to
their appearance under the microscope
granulocytes
• _______________
– many stained organelles giving them a
“grainy” appearance
agranulocytes – few or no organelles
• _______________
Specific Jobs of Leukocytes Granulocytes
Basophils
• ____________
– produce histamine
leading to inflammatory response
• Rarest population
Neutrophils
• _____________
– phagocytose
bacteria and viruses
• 3-6 nuclear lobes
Eosinophils
• _____________
– lead attack
against parasitic worms
• Bilobed nucleus
• Also phagocytose bacteria
Specific Jobs of Leukocytes - Lymphocytes
• Lymphocytes – produce antibodies against
specific invaders
• B lymphocytes – produce antibodies to pathogens
• T lymphocytes
• produce cytokines that direct immune response (CD4
cells)
• Destroy infected cells (CD8 cells)
• These cells are the heart of adaptive immunity,
as they and their clones will “remember” the
antibodies they produced
Specific Jobs of Leukocytes - Monocytes
phagocytize
• Monocytes – function to ___________
bacteria and other invading pathogens
• Will mature into macrophages which can
leave the blood vessels and enter tissues
where pathogens frequently enter
diapedesis
(_____________)
Phagocytosis
• WBC’s (Macrophages, eosinophils
and neutrophils) surround and
engulf pathogens
• WBC then adheres to the
pathogen via binding of cell
membrane components
• This process can be facilitated by
opsonization- antibodies or other
proteins (complement) mark the
pathogen for death by sticking to it
WBC
Germ
Antibodies and
protein “markers”
from host
Opsonization
Phagocytosis
• Once adherence is complete, pathogens are engulfed via endocytosis,
which forms a phagosome
• The contents of the phagosome are then digested by merging with a
lysosome (vesicle in the cell containing digestive enzymes)
Phagocytosis
Differential Hemocyte Count
• Depending on the pathogen, infection will cause changes in
the proportion of WBC’s in the blood
What type of infection does this person have?
Differential WBC Count
8000
7000
Cells/ul
6000
5000
4000
3000
Normal
2000
Infected
1000
0
1/7 of the Human population suffers from
worm infections – WHY?
Origins - Erythropoiesis
• Blood cells are made from stem cells
(Hemocytoblasts) in the bone marrow and
differentiate into:
• Erythrocytes
• Leukocytes
• Platelets
All red blood cells develop from undifferentiated
stem cells in the red bone marrow
(Notice the ejection of the nucleus)
White Blood cells also develop from undifferentiated
stem cells in the red bone marrow
Platelets
• Essential for blood clotting
• Form from a megakaryocyte
that breaks off bits of its
cytoplasm and membrane
• Cytoplasmic “chunks” enter
blood stream and form
platelets
Blood Typing
Erythrocytes
• Antigens (Agglutinogens) – surface glycoproteins that
are inherently different between blood types (4 types)
“B”
Antigen
“A”
Antigen
Type A
Type B
Type AB
Type O
Antibodies
• Proteins that are created by the immune system to
recognize “non-self” organisms/chemicals
• Antigens on bacteria, fungi, protozoans, other pathogens
or other molecules
• People with different blood types can develop
antibodies that will attack “non-self” antigens
erythrocytes
Blood Types and Antibodies
Blood Type
Antigens
Antibodies
_B
Type A
Y
Type A
_A_
Type B
Y
Type B
_A__AND __B_
Type AB
Type O
Type AB
Y Y
Type O
___none
What
happens if
blood types
are mixed in a
transfusion?
Antigen + Complementary
Antibody
Y
Type A
erythrocyte
“Anti – A”
antibody
=
This results in “agglutination”, or the sticking together of hemocytes
to their complement antibodies, causing blood cells to
stick together and clump
Rh Factor
• In addition to the glycoproteins that equate to blood
type (A,B) the “Rh” glycoprotein can be either present
or absent
• People that are “Rh negative” can have the antibodies
to the Rh antigen
• This is what is represented by the + or – in blood
types; (e.g. O+ = O blood type with RH factor
(antigen), and therefore no antibodies to Rh)
Rh Factor and Adaptive Immunity
• The immune system has a memory, after exposure to
an antigen, your body will “remember” what
antibodies to make to attack that antigen
• This becomes a problem in women that are Rhnegative, and are pregnant with an Rh positive baby
• Why?
Rh Factor and Adaptive Immunity
• After a first pregnancy, blood from the baby can “mix” with blood
from the mother during labor, C-section, even abortion
• If the baby is Rh+ and the mother Rh-, the mother’s body will produce
antibodies to Rh
• Future pregnancies could be at risk, therefore, immune modulators
must be administered (RhoGam)
Blood Typing Practice
• Go here to get practice performing transfusions in the context of
blood type
• Be sure to ask yourself WHY the outcomes happen in the different
scenarios
• http://www.nobelprize.org/educational/medicine/bloodtypinggame/
game/index.html
Clotting (Hemostasis)
• A coordinated series of events to stop the flow (loss) of blood
1. Vascular spasm
2. Platelet plug formation
3. Coagulation
Vascular Spasm
• Upon damage, the vessel responsible for
the loss of blood will constrict
(vasoconstriction)
• This is due to:
• Damage to smooth muscle lining the vessel
• Pain receptor stimulation
• Chemicals released by platelets and epithelial
cells lining the vessel
Platelet Plug Formation
• Platelets will clump together due to several clotting factors
• Platelets stick tenaciously to the collagen exposed in damaged blood vessels
• A large protein Factor 8 (with Von Willibrand factor) links platelets at the plug to
each other and to the collagen in the vessel wall
• ADP and serotonin released from platelets also increase the platelet aggregation
to form a clot
Coagulation
• The release of clotting factors changes
prothrombin (a plasma protein) into
thrombin (an enzyme)
• Thrombin catalyzes fibrinogen (also
present in plasma) into fibrin – a
molecular polymer that creates a
mesh to trap RBC’s and platelets
Fibrin mesh
Red Blood Cell
Clot Retraction
• Platelets contain actin and myosin that will
contract the clot (increases in density)
Normal Clot Retraction
• Platelet derived growth factor (PDGF)
• Stimulates the growth of collagen and
elastin that repair the damaged vessel
• An activated enzyme plasmin eventually
breaks down the fibrin after being activated
by factors derived from endothelial cells
surrounding the clot
Abnormal Clot Retraction
Clotting Issues
• Embolism – clot breaks from vessel wall
and moves through the blood vessels
• How can this be a problem?
• Clots can be broken up via anticoagulants
(aspirin, warfarin, heparin) which inhibits
clotting factors
Bleeding Disorders
• Thrombocytopaenia – low platelet
count
• How can this happen?
• Hemophilia – genetic disorder
(Mendelian) that results in low/no
production of clotting factors (proteins)
• How can this be treated? Potential
problems of treatment?
• Leukemia – excessive production of
leukocytes (non-functional)