2. Function of Circulatory System
Fundamental purpose of the circulatory system is to
transport substances from one place to another in the blood.
Functions of Circulatory System:
1. Transportation
-O2, CO2, nutrients, wastes, hormones, and heat
2. Protection
- role in inflammation = ↓ spread of infection
- white blood cells, antibodies, platelets;
3. Regulation
- Stabilize fluid distribution and pH
3. 18-3
Components & General Properties of
Blood
• Adults have 4-6 L of blood
– Contains two FORMED elements:
1. Plasma - a clear extracellular fluid
2. Formed Elements – cells and cell
fragments
6. 18-6
• Ratio of the formed elements to
plasma:
Accomplished by spinning a
sample of blood in a centifuge.
• Erythrocytes are densest,
typically 45% of total volume.
This is called the hematocrit or
packed cell volume.
• WBCs and platelets make up a
narrow zone (cream color)
called the buffy coat. About 1%
of total volume.
• Plasma about 55% of total
volume on top.
8. 18-8
Blood Plasma
Considered liquid connective tissue;
• Contains:
– Water
– Proteins
– Nutrients
– Electrolytes
– Nitrogenous wastes
– Hormones
– gases
Serum- when blood
clots and solids are
removed the
remaining fluid is
serum;
Serum is identical to
plasma except for the
absence of clotting
protein fibrinogen
10. 18-10
Plasma Proteins
Proteins are the most abundant plasma solute
by weight (6-9 g/dL)
Proteins play a variety of roles:
1. Clotting
2. Defense
3. Transport of solutes:
1. Iron
2. Copper
3. Lipids
4. Hormones
11. 18-11
Plasma Proteins
• 3 major categories of plasma proteins
1. albumins - most abundant
• Transports various solutes and buffer pH of plasma
• contributes to viscosity and osmolarity, influences blood
pressure, flow and fluid balance;
2. globulins (antibodies)
• provide immune system functions, transport, clotting
• alpha, beta and gamma globulins;
3. fibrinogen
• precursor of fibrin- a sticky protein that forms the
framework of a blood clot;
• Liver produces 4g protein/hour
12. 18-12
Nonprotein Components of Plasma
• Nitrogenous compounds
– amino acids
• from dietary protein or tissue breakdown
– nitrogenous wastes (urea)
• toxic end products of catabolism
• normally removed by the kidneys
• Nutrients
– glucose, vitamins, fats, minerals, phospholipids,
cholesterol;
• O2 and CO2 and nitrogen
• Electrolytes (another important component of plasma)
– Na+
makes up 90% of plasma cations
– Sodium is important for osmolarity of blood, influence on blood
volume and pressure.
14. 18-14
Blood Viscosity & Osmolarity
Two most important properties, arise from formed elements and plasma
composition.
• Viscosity - resistance of a fluid to flow resulting from a
cohesions of its particles.
• whole blood 5 times as viscous as water, due mainly to RBCs
• Plasma 2x as viscous as water, due to its proteins.
• Viscosity is important to circulatory function because it
partially governs the flow of blood through the vessels.
• RBC or protein deficiency = flows easily
• Excess of above = flows sluggishly
15. 18-15
Blood Viscosity & Osmolarity
• Osmolarity
– total molarity of dissolved particles that cannot
pass through the blood vessel walls.
– Nourishment of surrounding cells and waste
removal is dependent upon substances passing
through the capillary walls.
16. 18-16
Blood Viscosity & Osmolarity
high osmolarity (blood)
• causes fluid absorption into blood, raises BP
low osmolarity (blood)
• causes fluid to remain in tissues, may result in
edema, drop BP to dangerous levels because of the
amount of water lost from the blood stream.
• Osmolarity is a product of sodium ions,
protein, and RBCs
17. 18-17
Kwashiorkor
• Hypoproteinemia:
deficiency of plasma
protein.
– Extreme starvation
– Dietary protein deficiency
– Liver disease (synthesis)
– Kidney disease
– Severe burns
As protein content ↓ in
blood, = ↓ osmolarity =
bloodstream loses more
fluid to the tissues than it
reabsorbs by osmosis.
18. 18-18
How Blood is Produced
Hemopoiesis – production of blood (esp. elements)
• Adult produces 400 billion platelets, 200 billion RBCs and 10 billion WBCs
every day
• Hemopoietic tissues produce blood cells
Lymphocytes are also produced by lymphatic tissues and
organs (thymus, tonsils, lymph nodes, spleen)
– Blood formation in bone marrow = myeloid hemopoiesis
– Blood formation in lymphatic organs = lymphoid
hemopoiesis
19. How Blood is Produced
All fromed elements trace their origins to a common
type of bone marrow stem cell called pluripotent
stem cell (PPSC).
So named because they have the potential to
develop into multiple mature cell types.
21. 18-21
Form & Function
Disc-shaped cell with thick rim sunken center
– Lose most of organelles during development;
– Lack mitochondria, rely on anaerobic
fermentation to produce ATP – not aerobic
respiration;
– Lack nucleus and DNA = incapable of protein
synthesis and mitosis.
22. Form & Function
• Glycoproteins & glycolipids on surface
determine a persons blood type;
• Contain cytoskeletal proteins called spectrin
& actin give membrane resilience &
durability;
• Contains 33% hemoglobin:
– Purpose:
• oxygen transport,
• CO2 transport and
• buffering pH of blood
23. Form & Function
• Biconcave shape allows for a greater ratio of
surface to volume, this enables O2 and CO2 to
diffuse quickly to and from the hemoglobin.
• Cytoplasm contain CAH (Carbonic Anhydrase);
plays a role in gas transport & pH balance,
catalyzes …
CO2 + H2O H2CO3→
→
25. 18-25
Hemoglobin (Hb) Structure
• Contains 4 protein chains
called globins
– 2 alpha and 2 beta chains
• fetal Hb - gamma replace
beta chains; binds O2 better
• Each chain is conjugated
into a heme group (4 total)
– Binds O2 to Fe2+
at center;
• So… each hemoglobin
molecule can carry four O2
26. Quantities of Erythrocytes and Hemoglobin
• RBC count and hemoglobin concentration
indicate amount of O2 blood can carry;
3 common measurements are:
1. Hematocrit
2. hemoglobin concentration
3. RBC count
27. 18-27
Quantities of Erythrocytes and
Hemoglobin
Hematocrit (packed cell volume) - % of blood
composed of RBCs
• men 42- 52% cells; women 37- 48% cells
Hemoglobin concentration of whole blood
• men 13-18g/dL; women 12-16g/dL
RBC count
• men 4.6-6.2 million/µL; women 4-2-5.4 million/µL
• Values are lower in women
– androgens stimulate RBC production (higher in men);
– women have periodic menstrual losses;
– Hematocrit is inversely proportional to % body fat, which
is higher in women than men.
28. Erythrocyte Life Cycle
Average life span of a RBC is 120 days;
In a state of balance and stable RBC count,
birth to death of RBCs is about 2.5
million/sec or 20mL/day.
Erythrocyte production called Erythropoiesis
29. 18-29
Erythrocyte Production
Erythrocyte production called Erythropoiesis
• Development takes 3-5 days and Involves four
major developments:
1. reduction in cell size,
2. increase in cell number,
3. synthesis of hemoglobin, and
4. loss of nucleus and most organelles.
30. 18-30
Erythropoiesis
• Begins with pluripotent stem cell (PPSC) → commits to
becoming erythrocyte colony forming unit (ECFU).
• ECFU have receptors for erythropoietin (EPO) from kidneys,
• EPO stimulates ECFU to transform into Erythroblasts;
• Erythroblasts multiply and synthesize hemoglobin;
• At this point the nucleus disappears becoming a reticulocyte;
• Enter circulation, in about a day or two they become mature
erythrocytes;
– Normally 0.5 to 1.5% of circulating RBCs are reticulocytes
– % will change in response to different situations.
31. 18-31
Iron Metabolism
• Fe2+
- key nutritional requirement for erythropoiesis;
• Iron is lost daily through urine, feces, and bleeding;
• men 0.9 mg/day and women 1.7 mg/day
• low absorption requires consumption of 5-20 mg/day
• Dietary iron exists in two forms:
1. ferric (Fe3+
) ions (not absorbable)
2. ferrous (Fe2+
) ions (absorbable by S.I.)
Stomach acid converts Fe3+
to absorbable Fe2+
32. Iron Metabolism
Once converted to Fe2+
it binds with a protein called
gastroferritin and transports it to small intestine for
absorption;
Fe2+
gets absorbed into the blood and binds to plasma protein
called transferrin for transport.
Transported to bone, liver and other tissures.
1. Bone marrow uses Fe2+
for hemoglobin synthesis;
2. Muscles use it to make the oxygen-storage protein myoglobin;
3. cells use it to make electron-transport molecules (cytochromes)
Once in the liver, the surplus iron binds with a protein called
apoferritin, forming a iron-storage complex called ferritin;
Liver will release iron as needed.
33.
34. 18-34
Nutritional Needs for Erythropoiesis
Vitamin B12 and folic acid
– rapid cell division & DNA synthesis
Vitamin C and Cu
– cofactors for enzymes synthesizing hemoglobin
35. 18-35
Erythrocyte Homeostasis
• Negative feedback control
– drop in RBC count causes
hypoxemia (low blood O2);
– Detected by kidneys, ↑ EPO;
– EPO stimulates erythroblast
production;
– RBC count ↑ in 3 - 4 days;
• Other stimulus for erythropoiesis
– low levels O2;
– increase in exercise;
Emphysema-loss of lung tissue,
could result in polycythemia.
36. Erythrocytes Death & Disposal
As RBC age its membrane proteins begin to break down
(spectrin), causing them to become fragile;
Since they lack a nucleus, ribosomes etc, they are unable to
synthesis more spectrin;
The RBC die in the spleen “erythrocyte grave-yard”;
The spleen is made up of narrow channels that test the ability
of older RBC to squeeze through;
If unable to squeeze through, they become trapped and
destroyed.
37. 18-37
Erythrocytes Death & Disposal
Hemolysis – rupture of RBCs = release hemoglobin
and leaves empty plasma membranes;
• Macrophages in spleen
– digest membrane bits
– separate heme from globin
• globins hydrolyzed into amino acids
• iron removed from heme
– heme pigment converted to biliverdin (green);
– biliverdin converted to bilirubin (yellow-green);
– Macrophages release bilirubin into blood plasma, which binds to
albumin;
– Liver removes it from the albumin, & sends it to the gall bladder;
» concentrated in gall bladder: released into small intestine;
bacteria create urobilinogen (brown feces)
39. 18-39
Erythrocyte Disorders
1. Polycythemia - an excess of RBCs
– primary polycythemia
• cancer of erythropoietic cell line in red bone marrow
– RBC count as high as 11 million/µL; hematocrit 80%
– secondary polycythemia
• from dehydration, smoking, emphysema, high altitude,
or physical conditioning
– RBC count up to 8 million/µL
• Dangers of polycythemia
– increased blood volume, pressure, viscosity
• can lead to embolism, stroke or heart failure
40. Erythrocyte Disorders
2. Anemia
Three Catagories:
1. Inadaquate erythropoiesis or hemoglobin
synthesis;
2. Hemorrhagic anemia – from prolonged
bleeding;
3. Hemolytic anemia – from RBC destruction
42. 18-42
Anemia
Three Potential Consequences:
1.Tissue hypoxia and necrosis
- shortness of breath and lethargic
- skin pallid due to hemoglobin deficiency
- severe anemic hypoxia = life threatening
- lead to necrosis of brain, heart, kidneys
2. Blood osmolarity is reduced (tissue edema)
3. Blood viscosity is reduced (blood puts up less resistance to
flow so the heart beats faster than normal and cardiac failure can occur
and pressure drops)
43. 18-43
Sickle-Cell Disease
• Hereditary Hb ‘defect’ of African Americans
– sickle-cell trait -
• individual has resistance to malaria
– sickle-cell disease
• individual has shortened life
– in low O2 concentrations HbS causes cell elongation and sickle
shape
– cell stickiness causes agglutination and blocked vessels
– intense pain; kidney and heart failure; paralysis; stroke
45. 18-45
Blood Types
• Based on the interactions between antigens and
antibodies
• Antigens
– unique molecules on cell surface
• used to distinguish self from foreign
• foreign antigens generate immune response
• Antibodies
– secreted by plasma cells
• as part of immune response to foreign matter
• Agglutination
– antibody molecule binding to antigens
– causes clumping
– Repetition of this process produces large antigen-antibody complexes
46. 18-46
ABO Group
• A, B, AB, and O form ABO blood type.
Your blood type is determined by the hereditary presence or
absence of antigen A or antigen B on your RBCs.
Antibodies of the ABO group react against any A or B
antigens on the RBC surface.
- causing clumping (agglutination)
47. 18-47
ABO Group
• Your ABO blood type is determined by
presence or absence of antigens on RBCs
– type A person has A antigens
– type B person has B antigens
– type AB has both A & Bantigens
– type O has no antigens
• most common - type O
• rarest - type AB
49. ABO Group
The antibody that reacts with antigen A is called
alpha agglutinin or anti A.
The antibody that reacts with antigen B is called beta
agglutinin or anti B.
To determine ones blood type, a drop of blood is put
in a pool of anti A serum and anti B serum;
Looking for agglutination.
51. 18-51
ABO Group
• Person with type A (anti-B) blood
– Never receive from Type B or AB
• Person with type B (anti-A) blood
– Never receive from Type A or AB
• Person with type O (anti-A and Anti-B) blood
– Never receive from Type A, B, or AB
52. Type A Type B Type AB
Type O
RBC: antigen A antigen B antigens A,B none
Plasma: anti-B anti-A none anti-A,
antibodies antibodies anti-B
antibodies
Blood Types
55. 18-55
Universal Donors and Recipients
• Universal donor
– Type O
– lacks RBC antigens
• Universal recipient
– Type AB
– lacks plasma antibodies; no anti- A or B
56. 18-56
Leukocytes (WBCs)
• 5,000 to 10,000 WBCs/µL
• Conspicuous nucleus
• Travel in blood before migrating to
connective tissue
• Protect against pathogens
57. 18-57
Leukocyte Descriptions
• Granulocytes
– neutrophils (60-70%) (aka polymorphonuclear leukocytes)
• fine granules in cytoplasm; 3 to 5 lobed nucleus
– eosinophils (2-4%)
• large rosy-orange granules; bilobed nucleus
– basophils (<1%)
• large, abundant, violet granules (obscure a large S-shaped
nucleus)
• Agranulocytes
– lymphocytes (25-33%)
• variable amounts of bluish cytoplasm (scanty to abundant);
ovoid/round, uniform dark violet nucleus
– monocytes (3-8%)
• largest WBC; ovoid, kidney-, or horseshoe- shaped nucleus
59. Granulocyte Functions
• Eosinophils (↑ in parasitic infections, allergies, diseases of spleen and
CNS)
– phagocytosis of antigen-antibody complexes,
allergens and inflammatory chemicals
– release enzymes to destroy parasites
62. 18-62
Agranulocyte Functions
• Lymphocytes (↑ in diverse infections and immune
responses)
– destroy cells (cancer, foreign, and virally infected cells)
– “present” antigens to activate other immune cells
– coordinate actions of other immune cells
– secrete antibodies and provide immune memory
63. Agranulocyte Functions
• Monocytes (↑ in viral infections and inflammation)
– differentiate into macrophages
– phagocytize pathogens and debris
– “present” antigens to activate other immune cells
65. 18-65
Complete Blood Count
• Hematocrit
• Hemoglobin concentration
• Total count for RBCs, reticulocytes, WBCs,
and platelets
• Differential WBC count
• RBC size and hemoglobin concentration per
RBC
66. 18-66
Leukocyte Life Cycle
• Leukopoiesis- production of WBC
– Begins with pluripotent stem cell – that differentiates into
distinct type of colony-forming units (CFU);
– CFU Types:
• Eosinophilic CFU, Basophilic CFU, neurtophilic CFU, monocytic CFU, and
lymphocytic CFU.
– CFU differentiate into specific cell lines:
• myeloblasts – differentiate into neutrophils, eosinophils, basophil
• monoblasts – differentiate into monocytes
• lymphoblasts differentriate into B and T lymphocytes and NK
cells
68. • Red bone marrow stores and releases
granulocytes and monocytes until needed.
• Circulating WBCs do not stay in bloodstream
– granulocytes circulate for 8 hours and then migrate into
the tissues & live for about 5 days;
– monocytes circulate for about 10-20 hours, migrate ino
the tissues, transform into macrophages and live for
several years;
– WBCs provide long-term immunity (decades)
69. 18-69
Leukocyte Disorders
• Normal WBC count is 5000 – 10,000 WBC/µL
• Leukopenia - low WBC count (<5000/µL)
– causes: radiation sickness, lead, mercury poisoning,
infectious disease (MMR, varicella, polio, AIDS), anti-
cancer drugs
– effects: elevated risk of infection and cancer
• Leukocytosis = high WBC count (>10,000/µL)
– causes: infection, allergy and disease, dehydration and
emotional disturbances.
– differential count - distinguishes % of each cell type
• High neurtophil = bacterial infection, ie appendicitis
• High eosinophil = allergy or parasitic infection, ie tapeworm
70. 18-70
Leukocyte Disorders
• Leukemia = cancer of hemopoietic tissue
– Increase of circulating leukocytes and their
precursors
• Treatment = chemo, marrow transplant
along with controlled side effects such as
anemia, hemorrhaging, and infection.
72. Platelets & Hemostasis-Control of bleeding
Hemostasis – cessation of bleeding (stop the
bleeding);
Platelets may not stop the hemorrhaging of
large vessels but are effective on closing
smaller vessels.
73. 18-73
Platelets
• Not cells but small fragments of marrow cells
called megakaryocytes;
• Normal Count - 130,000 to 400,000 platelets/µL
• Internal structures include:
– lysosomes,
– mitochondria,
– granules (filled with platelet secretions),
– Platelet Production -Thrombopoiesis
74. Platelet Functions
1. Secrete vasoconstrictors- chemical that causes
spasmodic contraction of broken blood vessels;
2. Stick together to form a temporary platelet plug;
3. Secrete procoagulants (clotting factors);
75. 18-75
Platelet Production -Thrombopoiesis
• Stem cells develop receptors for the hormone
thrombopoietin, thus becoming megakaryoblasts;
• Megakaryoblasts
– repeatedly replicate DNA without dividing cytoplasm;
– Result is a gigantic cell called megakaryocyte;
• Megakaryocyte
– infoldings of cytoplasm splits off cell fragments that
enter bloodstream as platelets, those live for 10 days;
– 25 – 40% are stored in spleen & released as needed.
77. 18-77
1. Hemostasis - Vascular Spasm (Immediate)
• Causes
– pain receptors
• some directly innervate nearby blood vessels,
causing constriction
– Injury to smooth muscle will vasoconstrict
– platelets release serotonin (vasoconstrictor)
• Effects
– prompt constriction of a broken vessel
• pain receptors - short duration (minutes)
– provides time for other two clotting pathways
78. 18-78
2. Hemostasis -Platelet Plug Formation
• Endothelium smooth, coated with prostacyclin
• Platelet plug formation
– broken vessel exposes collagen
– platelet pseudopods stick to damaged vessel and other platelets
– pseudopods contract and draw walls of vessel together forming a
platelet plug
As platelets aggregate they degranulate releasing factors that
promote hemostasis;
• serotonin is a vasoconstrictor
• ADP attracts and degranulates more platelets
• thromboxane A2, promotes aggregation, degranulation and
vasoconstriction
– positive feedback cycle is active until break in vessel is sealed
80. 18-80
3. Hemostasis - Coagulation
• Coagulation (clotting) - most effective defense
against bleeding
– Conversion of the plasma protein fibrinogen into fibrin
threads to form framework of clot;
• Two reaction mechanisms to coagulation:
1.Extrinsic Mechanism
2.Intrinsic Mechanism
81. Coagulation
Extrinsic Mechanism:
- initiated by clotting factors released by damaged blood vessel and
perivascular tissues;
- extrinsic mean that these factors came from a source other then the
blood.
Intrinsic Mechanism:
- clotting factors that are in the blood.
These clotting factors are called procoagulants, most are proteins that are
in an inactive form, until one is activated, thus activating the next one
and so on,
Producing a reaction cascade – a series of reactions.
82. 18-82
Coagulation Pathways
• Extrinsic pathway
– initiated by tissue
thromboplastin;
– cascade to factor VII, V
and X (fewer steps),
– 15 seconds to start clot.
• Intrinsic pathway
– Everything needed to
initiate it is present in
the plasma or platelets;
– initiated by factor XII;
– cascade to factor XI to
IX to VIII to X;
– 3-6 minutes for clot to
form.
• Calcium required for
either pathway
Fibrinogen
83. 18-83
Completion of Coagulation
• Activation of Factor X
– leads to production of prothrombin activator
• Prothrombin activator
– converts prothrombin to thrombin
• Thrombin
– converts fibrinogen into fibrin
84.
85. 18-85
Fate of Blood Clots
• After clot has formed the platelet pseudopods adhere to the
fibrin and contract = drawing edges of blood vessels
together
Clot retraction occurs within 30 minutes
• Platelets & endothelial cells secrete:
– Platelet-derived growth factor (PDGF) which is a …
– mitotic stimulant for fibroblasts and smooth muscle to multiply and
repair damaged vessel;
87. 18-87
Prevention of Inappropriate Clotting
1. Platelet repulsion
– platelets do not adhere to prostacyclin-coated
endothelium of undamaged blood vessels;
2. Dilution
– Small amounts of thrombin form spontaneously in
plasma;
– At normal rate of blood flow the thrombin is diluted;
• heart slowing in shock can result in clot formation
3. Natural anticoagulants
– heparin (from basophils and mast cells) interferes with
formation of prothrombin activator
– antithrombin (from liver) deactivates thrombin before it can
act on fibrinogen
88. 18-88
Hemophilia
• Genetic lack of any clotting factor affects
coagulation
• TYPES:
– hemophilia A missing factor VIII (83% of cases)
– hemophilia B missing factor IX (15% of cases)
• Physical exertion causes bleeding and
excruciating pain
– transfusion of plasma or purified clotting factors
– factor VIII produced by transgenic bacteria
89. 18-89
Coagulation Disorders
• Embolism - clot traveling in a vessel
• Thrombosis - abnormal clotting in unbroken
vessel
– most likely to occur in leg veins of inactive
people
– pulmonary embolism - clot may break free,
travel from veins to lungs
• Infarction may occur if clot blocks blood
supply to an organ (MI or stroke)
– 650,000 Americans die annually of
thromboembolism