Blood
Chapter 17
Review: What is Blood?
• Only fluid connective tissue
– Plasma
– Formed elements
• Erythrocytes (RBC’s)
• Leukocytes (WBC’s)
• Thrombocytes (platelets)
• Hematocrit is % of RBC’s out of total blood volume
2
Centrifuge
Plasma
(55% of whole blood)
Buffy coat:
leukocyctes and
platelets
(<1% of whole blood)
1
Withdraw blood
and place in tube
Erythrocytes
(45% of whole blood)
Formed
elements
Figure 17.1
Physical Characteristics
• pH 7.35 – 7.45
• Temperature about 38°C (normal 37°C)
• Approximately 8% body weight
• Males: 5 – 6 L
• Females: 4 – 5 L
• Human blood is NEVER blue
– Scarlet (oxygen-rich)
– Dark red (oxygen-poor)
Functions
• Distribution
– O2 and nutrients in
– CO2 and wastes out
– Hormones to target cells
• Regulation
– Body temp
• Absorb/distribute heat
– pH
• Buffer systems
• Bicarbonate atoms
– Fluid volumes
• Salts and proteins
• Protection
– Prevent blood loss
• Clot formation
• Platelets and proteins
– Prevent infection
• Fight foreign invaders
• Antibodies, WBC’s, and
complement proteins
Plasma
• 90% water
• 100+ dissolved solutes
– Proteins
• Albumin: osmotic pressure
• Globulin: antibodies and transport proteins
• Fibrinogen: role in clotting
–
–
–
–
Nutrients: fuel from digestive tract
Electrolytes: osmotic pressure and pH
Gases: O2 and bicarbonate ions bound to hemoglobin
Hormones
Formed Elements
• ‘Cell’ types
– WBC’s are complete cells
– RBC’s without nuclei or organelles
– Platelets are cell fragments
• Live only a few days
• Don’t divide, but are renewable
– Where does hematopoiesis occur?
Erythrocytes (RBC’s)
• Biconcave shape
– Large SA to small volume
– Flexibility to pass through vessels
• Primarily composed of hemoglobin
– Readily binds/transports O2 and CO2
• Generate ATP anaerobically
– Means what?
– No mitochondria
Hemoglobin (Hb)
• Transports respiratory gases
– Globin protein bound to 4 hemes containing iron
– 1 RBC about 250 million Hb molecules = 1billion O2
• Normal values
– 14-20g/100ml infants
– 13-18g/100ml males
– 12-16g/100ml females
• Specific types
– Oxyhemoglobin
– Deoxyhemoglobin
– Carbaminoglobin (binds amine groups)
Hematopoiesis
• Hemocytoblasts (stem cells) commit to a
formed element
– Unchangeable after
– Growth factors and hormones ‘push’ to specialize
• Erythropoiesis 15 days (+ 2 to mature)
• Leukopoiesis discussed later
Hormonal Control of Erythropoiesis
• Erythropoietin (EPO) release by kidneys
– Decreased RBC numbers (trauma)
– Decreased O2 availability (altitude)
– Increased O2 demand (exercise)
– Insufficient hemoglobin (iron deficiency)
• EPO inhibited by high O2 or RBC count
– Type of feedback?
• Kidney fails = no EPO = low RBC count
– EPO injections
• Abuse by athletes to increase hematocrit
Erythropoiesis Homeostasis
Start
Normal blood oxygen levels
Increases
O2-carrying
ability of
blood
Enhanced
erythropoiesis
increases
RBC count
Stimulus: Hypoxia due
to decreased RBC
count, decreased
availability of O2 to
blood, or increased
tissue demands for O2
Reduces O2
levels in
blood
Erythropoietin
stimulates red
bone marrow
Kidney (and liver to
a smaller extent)
releases
erythropoietin
Dietary Regulation
• Iron is key
– 65% stored in hemoglobin (Hb)
– Free ions are toxic, so stored bound to proteins
– Some lost daily
• B12 and folic acid
– Necessary for DNA synthesis
– Roles in mitosis
• AA’s, lipids, and carbs too
Life and Death of Erythrocytes
• 100 – 120 day
– Cells age and Hb degenerates
– Engulfed by macrophages
• Components of Hb separated
– Heme  bilirubin  urobilinogen
• Bilirubin binds albumin and moves to liver
• From liver with bile to intestines
• Out in feces
– Iron saved and bound to protein for storage
– Globin metabolized to AA’s and into circulation
• See fig. 17.7
Erythrocyte Disorders
• Anemias: low O2carrying capacity; sign not disease
– Insufficient number of RBC’s
• Hemorrhagic anemia: blood loss; acute or chronic
• Hemolytic anemia: lysing of RBC’s early from parasites, mismatched
blood
• Aplastic anemia: disruption/destruction of red bone marrow
– Low Hb content
• Iron-deficiency anemia: inadequate iron intake
• Pernicious anemia: deficiency of B12 in diet
– Abnormal Hb
• Thalassemia: absent or faulty globin chain
• Sickle-cell anemia: defective gene codes for abnormal HB
• Polycythemias: high number of RBC’s
– Blood doping: remove and replace RBC’s = artificial polycythemia
– Secondary polycythemia: EPO increase when O2 levels down (high
altitude)
Leukocytes
• Not confined to blood vessels
• Chemotaxis to locate damage/infection
• Working WBC’s increase production of WBC’s
– Leukocytosis: high WBC count response to
infection
• General types
– Granulocytes
– Agranulocytes
Granulocytes
• Characteristics
– Larger and shorter-lived than RBC’s
– Phagocytic cells with lobed nuclei
– Cytoplasmic granules
• Types
– Neutrophils: body’s 1st phagocytic cells
– Eosinophils: fights parasitic worms and lessens
allergies by phagocytizing immune complexes
– Basophils: release histamine, a vasodilator
Agranulocytes
• Characteristics
– Spherical or kidney like nuclei
• Types
– Lymphocytes
• T cells: direct action against infected cells
• B cells: become cells that produce antibodies
– Monocytes
• Become macrophages after leaving blood supply
• Active phagocytes that also activate lymphocytes
Recognizing Leukocytes
Nuclei
Cytoplasm color
Neutrophils
3 – 6 lobes
light purple
Lymphocytes
large, circular,
purple
pale blue
Monocytes
U or kidney
shaped; purple
pale blue
Eosinophils
2 lobes; red
red/crimson
Basophils
U or S shaped;
purple
purple-black
Leukopoiesis
• All leukocytes originate
from hemocytoblasts
– Either myeloid or
lymphoid stem cell lines
• Myeloid stem cells
– Myeloblasts
– Monoblasts
• Lymphoid stem cells
– Lymphoblasts
• Similarities to
erythropoiesis
Hormonal Control of Leukopoiesis
• Interleukins
– Numbered (IL – 1, IL – 2, IL – 3, etc.)
• Colony-stimulating factors (CSFs)
– Named for the WBCs stimulated (granulocyte –
CSF)
• Hematopoietic factors from red bone marrow
and WBCs too
– Encourage maturation and division
– Used clinically after chemotheraphy, stem cell
transplants, or in AIDS patients
Leukocyte Disorders
• Leukpenia: abnormal WBC count; usually drug
(anticancer) induced
• Leukemia: cancerous conditions named for cell
type involved
– Bone marrow fills with cancerous leukocytes
– Numerous, nonfunctional WBCs produced
– Myelocytic (myeloblasts) or lymphocytic
(lymphocytes)
– Acute (blast-type cell) or chronic (later cell stage)
• Mononucleosis: epstein-barr virus; excessive
agranulocytes
Platelets
• Fragments of megakaryocytes
– Myeloid stem cell line
– Mitotic without cytokinesis
• Anucleate, live about 10 days
– Thin blue cytoplasm with a few purple granules
• Form temporary plugs during the clotting process
• Thrombopoietin regulates their production
Hemostasis
• Stoppage of bleeding
– Platelets, clotting factors, and injured tissues involved
• 3 phases
– Vascular spasm
• Rapid vasoconstriction of damaged vessel
• Efficiency increase with damage
– Plug formation
• Platelets bind to exposed collagen in damaged vessel
• Positive feedback of chemical messengers to attract more platelets
– Coagulation
• Liquid to gel
• Endothelial cells (extrinsic) and platelets (intrinsic) factors interact
with clotting factors
• Fibrous tissue eventually regrows to permanently seal
Coagulation Process
• Phase One: prothrombin activator pathways
– Intrinsic: factors in blood already
• Slower b/c many steps
– Extrinsic: tissue factor III (TFIII) outside blood in tissue
• Faster b/c skips steps
• Phase Two: thrombin activation
– Prothrombin activator catalyzes
– Prothrombin protein to thrombin enzyme
• Phase Three: fibrin mesh produced
– Fibrinogen catalyzed to fibrin
– Fibrin glues platelets together = clot
• Plasma becomes gel-like
– Factor XIII strengthens, sealing fibrin together
• Fig 17.14
http://www.astrographics.com/cgibin/ase/ase.cgi?affiliate=sciam&mode=display&gal
lery=3&type=medical&color=&keywords=&page=2
Clot Retraction and Repair
• Contractile proteins of proteins pull fibrin
strands together
– Stabilizes clot
• Platelet derived growth factor (PDGF)
stimulates smooth muscle and fibroblast
mitosis to rebuild wall
• Fibrinolysis dissolves clots
– Beneficial once healed
– Prevents build up in vessels
Controlling Clot Formation
• Limit growth through constant blood circulation
– Keeps [clotting factors] low in given locations
• Inhibit thrombin (intrinsic pathway too)
– Fibrin binds to prevent spread
– Antithrombin III (in plasma) inactivates
– Heparin enhances antithrombin III and inhibits
pathway
• Prevent clotting
– Antithrombics (NO) and undamaged vessel tissue
prevents platelet adhesion
– Blood thinner administration (aspirin, warfarin)
Hemostasis Disorders (Thromboembolytic)
• Undesirable clot formation
• Thrombus: clot in an unbroken blood vessel
– Can block normal blood flow = tissue death
– Coronary thrombus may cause heart attack
• Embolus: free floating clot
– Embolism once blood vessel is obstructed
– Pulmonary embolisms inhibit obtaining O2
– Cerebral embolisms may cause strokes
Hemostasis Disorders (Bleeding)
• Problems controlling bleeding
• Thrombocytopenia: platelet number is low
– Spontaneous bleeding all over body from mov’t
• Purple blotches on skin signify
• Liver can’t produce procoagulants
– Vitamin K deficiencies
– Other liver diseases
• Hemophilia: genetic disorder causing missing
clotting factors
– Type depends on affected factor
Human Blood Groups
• RBC membranes have glycoprotein antigens
on external surface
– Unique to individuals
– Recognized as foreign by other individual bodies
– Agglutinogens because they promote
agglutination (clumping)
• Presence or absence of antigens used to
classify blood groups
ABO Blood Groups
• Two antigens (A and B) on RBC surface in blood
– Blood types: A, B, AB, and O
• Two antibodies (anti-A and anti-B) in the plasma
– Non-complement to blood type produced
– See chart below
• Agglutinogens and complement antibodies can’t mix
w/o hemolytic reaction
• Newborns don’t start development until 2 months
after birth; complete between 8 and 10
Blood Type
Antigen A
Antigen B
Antibody anti-A
Antibody anti-B
A
Yes
No
No
Yes
B
No
Yes
Yes
No
O
No
No
Yes
Yes
AB
Yes
Yes
No
No
Receive ?
Rhesus (Rh) Blood Groups
• Multiple agglutinogens
– C, D, and E most common
– Named for monkey first discovered in
• Rh+ individuals have the D antigen
– Lack anti-Rh antibodies produced in plasma
– Can receive Rh+ or Rh- blood
• Rh- individuals lack the D antigen
– Lack anti-Rh, but can produce w/ Rh+ transfusion
• 1st occurrence = sensitization (no reaction), starts
production
• 2nd occurrence+ = attack and lysis of donor RBC’s
Transfusions Gone Wrong
• Transfusion reactions when mismatched blood
is exchanged
– Recipient's plasma attacks donor’s RBC’s
• Donor’s plasma may attack recipient’s RBC’s, but less
serious condition
– RBC’s hemolyse or phagocytize
• O2 carrying capacity drops
• Agglutination clogs small vessels
• Hb released into blood  kidney damage
possible
Diagnostic Blood Tests
• Hematocrit: % of RBC in blood
• Differential WBC count: different number of
WBC cells
• Platelet count: ability of blood to clot
• Complete blood count (CBC): number of
formed elements, hematocrit, Hb, and RBC
size
• Hemoglobin: amount in blood