BIO2305
The Blood
Fluids of the Body
Cells of the body utilize 2 fluids:
Blood
Composed of plasma and a variety of cells
Transports nutrients and wastes
Interstitial fluid
Bathes the cells of the body
Nutrients and oxygen diffuse from the blood into the interstitial
fluid & then into the cells
Wastes move in the reverse direction
Functions of Blood
Transportation
O2, CO2, metabolic wastes, nutrients, heat & hormones
Regulation
helps regulate pH through buffers systems (discussed in
later chapters)
Carbonic-Acid-Bicarbonate Buffer System
Phosphate buffer system
Protein buffer system
helps regulate body temperature
H2O in plasma has high specific heat capacity, buffering large fluctuations in temp
Vessels direct warm blood to where it’s needed, or to the skin for heat dissipation
Protection from disease & loss of blood
Physical Characteristics of Blood
Thicker (more viscous) than water, and flows more slowly than water
Temperature of 100.40 °F
pH 7.4 (7.35 - 7.45)
If pH 7 is neutral, blood at 7.4 is slightly alkaline
Average Blood volume:
Females: 4 – 5 Liters
Males: 5 – 6 Liters
Hormonal negative feedback systems maintain constant blood volume and pressure
Components of Blood
55% plasma
45% cells
99% RBCs
< 1% WBCs and platelets
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Hematocrit (Hct) & Hemoglobin (Hb)
Hematocrit (Hct) - percentage of blood volume occupied by RBCs
volume of red blood cells ÷ total blood volume
Normal Hematocrit range:
adult female: 38 - 46% (average of 42%)
adult male: 40 - 50% (average of 45%)
Hemoglobin (Hb) – the protein responsible
for transporting oxygen in the blood
Normal Hemoglobin range:
adult females: 12 – 16 g/1 dL of
blood
adult males: 13.5 – 18 g/1 dL of
blood
Anemia - not enough RBCs, hemoglobin
Polycythemia - too many RBCs (over 50%)
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Blood Plasma
Over 90% water
7% plasma proteins
created in liver
confined to bloodstream
albumin
Blood osmotic pressure
Transporter substances
globulins
Immunoglobulins (antibodies)
Defense against foreign proteins
fibrinogen
Clotting protein precursor
2% other substances
electrolytes, nutrients, hormones, gases,
waste products
Formed Elements of Blood
Red blood cells (erythrocytes)
Platelets (thrombocytes)
White blood cells (leukocytes)
Granular leukocytes
Neutrophils
Eosinophils
Basophils
Agranular leukocytes
Lymphocytes (T cells, B cells, and natural killer cells)
Monocytes
Normal RBC count: ~ 5 million/µL
Males: 5.4 million/µL
Female: 4.8 million/µL
Platelet count: 150,000-400,000/µL
WBC count: 5,000 - 10,000/µL
Ratio: 700 RBC’s and 40 Platelets to every 1 WBC.
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Hematopoiesis: Formation of Blood Cells
Most blood cell types need to be continually replaced
Blood cells die within hours, days, or weeks
Hematopoiesis (or hemopoiesis) – the
process of blood cell formation
In adults:
Occurs only in red marrow of flat bones
(pelvis, sternum, ribs, vertebrae, & skull, and
in ends of long bones)
Hematopoiesis of All Blood Cells
All blood cells develop from the same uncommitted stem cells in bone marrow
Red Blood Cells or Erythrocytes
Contain oxygen-carrying protein hemoglobin that gives
blood its red color
1/3 of cell’s weight is hemoglobin
Biconcave disk
Increased surface area:volume ratio
Flexibility for narrow passages
No nucleus or other organelles
No mitochondrial ATP formation
New RBCs enter circulation at 2-3 million/second
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Hemoglobin
Hemoglobin Molecule:
>> 4 globular protein subunits
>> each containing 1 heme group (red pigment)
>> each containing 1 iron ion (Fe+2)
>> each capable of binding (reversibly) to 1 oxygen (O2) molecule
Hemoglobin carrying capacity:
1 RBC = ~ 280 million Hemoglobins
1 Hemoglobin = 4 Heme Groups
1 Heme Group = 1 Iron atom = 1 O2 molecule
Therefore, 1 RBC can hold up to ~1.12 x 109 O2 molecules
The iron ion (Fe2+) wiithin a heme group is the site of oxygen binding.
The binding sites for CO2 molecules as well as H+ ions are located distal to the central O2 binding site
on the globular subunits.
At the tissue level, hemoglobin binds to H+ and CO2, which causes a conformational change in the
protein and facilitates the release of oxygen. H+ ions bind at various places on the protein, while carbon
dioxide binds at the α-amino groups within the α and β protein subunits.
Function of Hemoglobin
Each hemoglobin molecule can carry four O2 or CO2 molecules
Hemoglobin also acts as a buffer and balances pH of blood by transporting H+ ions away from tissues
Hemoglobin transports 23% of total CO2 waste from tissue cells to lungs for release
Forms of Hb:
Oxyhemoglobin: hemoglobin + O2
Deoxyhemoglobin: hemoglobin – O2
Carbaminohemoglobin: hemoglobin + CO2
Normal hemoglobin range
Infants have 14 to 20 g/1 dL of blood
Adult females have 12 to 16 g/1 dL of blood
Adult males have 13.5 to 18g/1 dL of blood
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Hemoglobin Affinity
CO2 vs O2
Deoxyhemoglobin’s affinity for carbon dioxide (CO2) is greater than its affinity for oxygen (O2)
Carbon dioxide (CO2) can lower O2-Hb affinity through changes in its partial pressure (pCO2) or
pH (carbonic acid reaction)
CO vs O2 (Carbon Monoxide Poisoning):
Hemoglobin’s affinity for carbon monoxide (CO) is 250 times greater than its affinity for
oxygen (O2)
CO is colorless, odorless, flammable, and highly toxic
CO binds irreversibly to the Fe2+ in hemoglobin. Treatment requires oxygen therapy, or
hyperbaric oxygen therapy, depending on severity of poisoning
The drop in Hb O2 saturation goes unnoticed for a while because chemoreceptors rely primarily
on [CO2] for the “urge to breathe”
Erythropoiesis: Production of RBCs
Multipotent stem cell differentiates into Proerythroblast
Proerythroblast begins producing hemoglobin, becoming
erythroblast
Erythroblast ejects nucleus, becoming a reticulocyte
Reticulocyte escapes from bone marrow, enters blood stream
In 1-2 days, reticulocyte ejects remaining organelles, becoming
Erythrocyte
Factors required for Erythropoiesis:
Erythropoietin (EPO) from kidneys
Vitamin B12 (cobalamin)
Iron (Fe)
Negative Feedback Control of Erythropoiesis
Hypoxia – inadequate oxygen supply to tissues
generalized hypoxia – systemic oxygen deprivation
tissue hypoxia – local oxygen deprivation
Common Causes:
High altitudes
decreased atmospheric pressure
Anemia
RBC or hemoglobin production < RBC destruction
Kidney response to hypoxia:
Release Erythropoietin (EPO)
Speeds up cell division of erythroblasts, and maturation and release of erythrocytes
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Negative Feedback Control of Erythropoiesis
Negative Feedback Control of Erythropoiesis
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RBC Life Cycle
WBC Physiology
Less numerous than RBCs
5,000 to 10,000 cells per µL of blood
1 WBC for every 700 RBC
Only 2% of total WBC population is in circulating blood at any given time
Heavily populate lymph, lymph nodes, skin, lungs, & spleen
Requires colony stimulating factor (local bone marrow/WBC hormone)
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Neutrophil Function
Fastest response of all WBC to bacteria and parasites
Direct actions against bacteria
release lysozymes which destroy/digest bacteria
release defensin proteins that act like antibiotics
release strong oxidants (bleach-like, strong chemicals ) that destroy bacteria
Basophil Function
Involved in inflammatory and allergy reactions
Leave capillaries (diapedesis) & enter tissues
Release heparin, histamine & serotonin
heighten the inflammatory response and account for
hypersensitivity (allergic) reaction
Heparin is a potent anti-coagulant that does not allow clotting
within vessels
Eosinophil Function
Leave capillaries to enter tissue fluid
Attack parasitic worms
Release histaminase
slows down inflammation caused by basophils
Phagocytize antibody-antigen complexes
Monocyte Function
Take longer to get to site of infection, but arrive in larger numbers
Become wandering macrophages, once they leave the capillaries
Destroy microbes and clean up dead tissue following an infection
Lymphocyte Functions
B cells
destroy bacteria and their toxins
turn into plasma cells that produce and release antibodies
T cells
attack viruses, fungi, transplanted organs, cancer cells
Natural killer cells (NKC)
attack many different microbes & some tumor cells
destroy foreign invaders by direct attack
Differential WBC Count
Detection of deviations in normal ranges of circulating WBCs
indicates immune response to infection, poisoning, leukemia, chemotherapy,
parasites, or allergens
Normal WBC counts:
Neutrophils: 60-70% (up if bacterial infection)
Lymphocyte: 20-25% (up if viral infection)
Monocytes: 3 - 8 % (up if fungal/viral infection)
Eosinophil: 2 - 4 % (up if parasite or allergy reaction)
Basophil: < 1% (up if allergy reaction)
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Thrombocytes (Platelets)
Disc-shape cell fragment with no nucleus,
Normal platelet count is 150,000-400,000/µL of blood.
Platelets form in bone marrow:
Myeloid stem cells eventually become megakaryocytes
whose cell fragments form platelets
Short life span - 5 to 9 days in bloodstream
Aged platelets removed by fixed macrophages in liver and spleen.
Platelets release ADP and other chemicals needed for platelet
plug formation
Hemostasis
Hemostasis - stoppage of bleeding in a quick & localized fashion when blood vessels are damaged
Prevents hemorrhage (loss of a large amount of blood)
Three major steps of Hemostasis:
1. Vascular spasm
2. Platelet Plug Formation
Aggregation and adhesion of platelets
3. Blood Clotting
Fibrin threads entangle platelets and RBCs to form blood clot
Vascular Spasm
Damage to blood vessel stimulates pain receptors
Reflex contraction of smooth muscle of small blood vessels
Can reduce blood loss for several hours, allowing other mechanisms to take over
Effective only for small blood vessels or arterioles, not major arteries
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Platelet plug formation
Platelet Plug Formation steps:
1. Platelet Adhesion
Platelets stick to exposed collagen of vessel
2. Platelet Release Reaction
Platelets extend projections
Platelets release Thromboxane A2, Serotonin & ADP activating other platelets
3. Platelet Aggregation
Platelets stick together forming a platelet plug
1) Platelet Adhesion
Platelets stick to exposed collagen underlying damaged endothelial cells in vessel wall
2) Platelet Release Reaction
Platelets activated by adhesion
Extend projections to make contact with each other
Release Thromboxane A2, Serotonin & ADP activating other platelets
Serotonin & Thromboxane A2 are vasoconstrictors decreasing blood flow through the injured
vessel.
ADP causes stickiness
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3) Platelet Aggregation
Activated platelets stick together and activate new platelets to form a mass called a platelet plug
Plug reinforced by fibrin threads formed during clotting process
Platelet plug formation
Blood Clotting
Blood drawn from the body thickens into a gel if not mixed with
anticoagulant
Blood separates into liquid (serum) and a clot of insoluble fibers
(fibrin) in which the blood cells are trapped
Substances required for clotting:
Ca+2
Clotting Factors (enzymes made by liver)
Substances released by platelets or damaged tissues
Clotting is a cascade of reactions
Each clotting factor activates the next, in a specific sequence,
resulting in the formation of fibrin threads
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Coagulation
A set of reactions in which blood is transformed from a liquid to
a gel
Coagulation follows intrinsic and extrinsic pathways
Common Pathway: The final three steps
Prothrombinase (Prothrombin activator) is formed
from Factor X
Prothrombinase converts Prothrombin into Thrombin
Thrombin catalyzes polymerization of Fibrinogen into a
Fibrin mesh
Two Pathways to Prothrombin Activator
May be initiated by either the intrinsic or extrinsic pathway
Triggered by tissue-damaging events
Involves a series of procoagulants
Each pathway cascades toward Factor X
Once Factor X has been activated, it complexes with Ca+2 ions,
PF3, and Factor V to form Prothrombin activator
(Prothrominase)
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Coagulation Phase of Hemostasis
Coagulation Pathway
Prothrombinase & Ca+2 catalyze the conversion of
Prothrombin to Thrombin
Thrombin & Ca+2 catalyze the polymerization of Fibrinogen
into Fibrin
Insoluble fibrin strands form the structural basis of a
clot
Fibrin causes RBCs and Platelets to become a gellike plug
Thrombin & Ca+2 also activate Factor XIII (F13) that:
Cross-links fibrin mesh
Strengthens and stabilizes the clot
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Coagulation Pathway
Clot Dissolution
Inactive plasminogen becomes plasmin, a fibrinolytic enzyme
Plasmin dissolves small clots at site of a completed repair
Clot formation remains localized
blood flow disperses clotting factors
Basophils release heparin (anticoagulant), preventing inappropriate clots
Intravascular Clotting
Thrombosis
Clot (thrombus) formed in an unbroken blood
vessel
Attached to rough inner lining of blood
vessel
Blood flows too slowly (stasis) allowing
clotting factors to build up locally &
cause coagulation
May dissolve spontaneously or dislodge &
travel
Embolus – free floating clot in the blood
Low dose aspirin blocks synthesis of thromboxane
A2 & reduces inappropriate clot formation,
Helps to prevent strokes, myocardial infarctions
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Blood Types
Agglutinogens – surface antigens on cells
Presence or absence of surface antigens determines Blood Type
Composed of glycoproteins & glycolipids
Antigens: A, B and Rh (D)
Agglutinins – antibodies in the plasma
Cross-reactions occur when antigens meet antibodies
ABO Blood Groups
Based on 2 glycolipid isoantigens called A and B found on the surface of RBCs
display only antigen A -- Blood Type A
display only antigen B -- Blood Type B
display both antigens A & B -- Blood Type AB
display neither antigen -- Blood Type O
Plasma contains isoantibodies or agglutinins to the A or B antigens not found in your blood
Anti-A antibody reacts with antigen A
Anti-B antibody reacts with antigen B
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Blood Type Testing
RH blood groups
Antigen was discovered in blood of Rhesus monkey
People with Rh isoantigens on RBC surface are Rh+
Normal plasma contains no anti-Rh antibodies
Antibodies develop only in Rh- blood type & only after
exposure to the antigen
Transfusion reaction upon 2nd exposure to the antigen
results in hemolysis of the Rh+ RBCs
HDN
Rh negative mom and Rh+ fetus will have mixing of blood at birth
Mom's body creates Rh antibodies unless she receives a RhoGam shot soon after first delivery,
miscarriage or abortion
In 2nd child, Hemolytic Disease of the Newborn may develop causing hemolysis of the fetal RBCs
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Universal Donors and Recipients
People with type AB+ blood called “universal recipients” since have no antibodies in plasma
AB+ blood cells contain all three surface antigens (A, B & D).
Hence, their immune system will not make antibodies to those markers.
Only true if cross match the blood for other antigens
People with type O- blood cell called “universal donors” since they have no antigens on their cells
O- RBCs have no surface antigens.
RBCs are “naked” and remain undetected by recipient immune systems.
Anemia = Not Enough RBCs
Symptoms
oxygen-carrying capacity of blood is reduced
fatigue, cold intolerance & paleness
Types of anemia:
iron-deficiency =lack of absorption or loss of iron
pernicious = lack of intrinsic factor for B12 absorption
hemorrhagic = loss of RBCs due to bleeding (ulcer)
hemolytic = defects in cell membranes cause rupture
thalassemia = hereditary deficiency of hemoglobin
aplastic = destruction of bone marrow (radiation/toxins)
Sickle-cell Anemia (SCA)
Genetic defect in hemoglobin molecule (Hb-S) that changes 2 amino acids
at low very O2 levels, RBC is deformed by changes in hemoglobin molecule within the RBC
sickle-shaped cells rupture easily = causing anemia & clots
Found among populations in malaria belt
Mediterranean Europe, sub-Saharan Africa & Asia
Person with only one sickle cell gene
increased resistance to malaria because RBC membranes leak K+ & lowered levels of K+ kill the
parasite infecting the red blood cells
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Hemophilia
Hemophilia - inherited deficiency of genes for clotting factors synthesis
bleeding spontaneously or after minor trauma
subcutaneous & intramuscular hemorrhaging
nosebleeds, blood in urine, articular bleeding & pain
Types:
Hemophilia A lacks factor VIII (males only)
most common
Hemophilia B lacks factor IX (males only)
Hemophilia C (males & females)
less severe because alternate clotting activator exists
Treatment is transfusions of fresh plasma or concentrates of the missing clotting factor
Leukemia
Acute leukemia
uncontrolled production of immature leukocytes
crowding out of normal red bone marrow cells by production of immature WBC
prevents production of RBC & platelets
Chronic leukemia
accumulation of mature WBC in bloodstream because they do not die
classified by type of WBC that is predominant---monocytic, lymphocytic.
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