100 m 
1s
1 mm 
100 s
1 cm
 10000 s
Transport System of the Body:
distance = time2
Transport System of the Body:
O2 / Energy
O2
O2
Nutrients
Waste
CO2
O2 / Energy
Nutrients
Waste
CO2
Diffusion
Source
Source
Cell
Cell
TOO MUCH
TIME
Bulk flow
(pressure)
External environment:
External environment:
Sink
CO2
/ Waste
CO2 / Waste
Sink
O2 / Nutrients
O2 / Nutrients
CO2 / Waste
CO2 / Waste
Cardiovascular System – Blood
Cardiovascular System:
Blood
Blood:
• Only fluid tissue in body (connective tissue)
• pH = 7.35 – 7.45 (slightly alkaline)
• Temp. slightly higher than body temp. (38°C / 100.4°F)
• ~ 8% body weight (♂ = 5-6 L; ♀ = 4-5 L)
Function (“River of Life”):
1) Distribution
• Delivers oxygen / nutrients
• Carries away metabolic wastes
• Transports hormones
Bloodletting a
common medical
treatment in the
Middle Ages
2) Regulation
• Maintains body temperature / pH
• Maintains fluid volumes
3) Protection
• Prevents blood loss (e.g., clot formation)
• Prevents infection (e.g., antibodies)
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
1) Formed Elements (living
Serum:
Plasma minus
clotting proteins
Blood Components:
A) Plasma
cells)
• Erythrocytes (RBC’s)
• Distributes materials / heat
• Leukocytes (WBC’s)
• Platelets
Composition:
Plasma
Hematocrit:
% of whole blood containing
formed elements
Buffy Coat
Males ~ 47%
Females ~ 42%
(~ 1%)
• Non-cellular fluid matrix
(dissolved proteins)
(Primarily produced
by liver)
B) Protein (~ 8%)
60%
Formed
elements
2) Plasma
A) Water (~ 90%)
Erythrocytes
(~ 45%)
(precisely maintained)
36%
4%
Albumin
Globulins
Fibrinogen
• Osmotic pressure
• Transport
• Transport ( / )
• Antibodies ()
• Clotting protein
C) Other solutes (~ 2%; >100 different solutes present; Table 17.1)
• Organic nutrients (e.g., glucose)
• Electrolytes (e.g., sodium)
• Nitrogenous waste (e.g., urea)
• Respiratory gases (e.g., O2)
1
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
Blood Components:
B) Erythrocytes (red blood cells – RBCs)
B) Erythrocytes (red blood cells – RBCs)
• Small (~ 7 m); biconcave (“certs”)
• Anucleate (lacking nucleus); few organelles
• Contain hemoglobin (O2 / CO2 transport protein)
Structure complements function
Shape maintained by network
of proteins (e.g., spectrin)
1) Small size and shape equates to large
surface area / volume
250 million / cell
Rapid respiratory gas loading / unloading
4 globins / hemoglobin
2) 97% of cell volume is hemoglobin
(2  chains; 2  chains)
(~ 250 million hemoglobin)
= 4 molecules O2
Mass transport of respiratory gases
Why maintain hemoglobin
in erythrocytes?
3) Lack mitochondria
(don’t burn oxygen)
Efficient transport of respiratory gases
1) Leakage through capillary walls
2) Viscosity / osmotic pressure issues
Heme (O2-binding
pigment w/ iron)
+ Globin (protein)
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures 17.3 / 17.14
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
Blood Components:
B) Erythrocytes (red blood cells – RBCs)
B) Erythrocytes (red blood cells – RBCs)
Erythropoiesis (red blood cell formation):
Entire process takes
~ 15 days
Erythropoiesis (red blood cell formation):
• ~ 2 million RBCs produced per second
• Formation occurs in red bone marrow
(ribosome factory)
High
Hemocytoblast
Vertebra
Sternum
Myeloid stem cell
Erythroblast
(stem cell)
Axial skeleton
Ribs
Reticulocyte Count:
Provide rough index of RBC
formation rate
Femur
Long bones
Tibia
Low
(nucleus
ejected)
Young
(enters blood stream)
Old
1 – 2 % of RBCs
Age (years)
Erythrocyte
Reticulocyte
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
B) Erythrocytes (red blood cells – RBCs)
Normoblast
(~ 85%)
(~ 15%)
Blood Components:
Free iron ions toxic!
B) Erythrocytes (red blood cells – RBCs)
• Acts as a catalyst for
the formation of
free radicals
Produced by the kidney
and liver
Erythropoiesis (red blood cell formation):
Erythropoiesis (red blood cell formation):
• Regulated hormonally by erythropoietin
• Dietary requirements must be met for normal RBC formation
1) RBC loss
2)  hemoglobin
Hypoxia
(-)
3) Low O2
Normal Blood Oxygen Level
Reduced O2
level in blood
Increased O2
level in blood
Iron:
(hemoglobin synthesis)
• Stored in liver & spleen in protein-iron
complexes ferritin and hemosiderin
Ferritin
(24 protein subunits)
• Transported in blood bound to transferrin
RBCs mature
more rapidly
Erythropoietin stimulates
bone marrow
Kidney releases
erythropoietin
Vitamin B12 and folic acid
necessary for proper DNA synthesis
Transferrin
(Glycoprotein; 2 binding sites)
2
Cardiovascular System – Blood
Blood Components:
Cardiovascular System – Blood
B) Erythrocytes (red blood cells – RBCs)
Pathophysiology:
Blood Components:
Jaundice:
Yellowing of skin due to
bilirubin deposition
Anemia
B) Erythrocytes (red blood cells – RBCs)
( oxygen carrying capacity of blood)
Destruction of Erythrocytes
Decreased
number of RBCs
• Lose flexibility
Hemorrhagic anemia
(blood loss)
Hemolytic anemia
(RBC rupture)
Microcytes
• Iron salvages; stored for re-use
• Heme group degraded to bilirubin
(captured by liver;
released via gallbladder)
Bilirubin
(metabolized in
large Intestine)
Urobilinogen
• “Old” RBCs engulfed by macrophages
in spleen / liver
(exits in feces)
Decreased
hemoglobin content
Macrocytes
Iron-deficiency anemia
(inadequate intake of iron)
Pernicious anemia
(deficiency of vitamin B12)
Sickle-cell anemia
(genetic mutation – abnormal globin)
Thalassemias
(genetic mutation – missing globin)
(yellow pigment)
Stercobilin (brown pigment)
Abnormal
hemoglobin
• Globins recycled to amino acids
Cardiovascular System – Blood
Cardiovascular System – Blood
Pathophysiology:
Blood Components:
Blood Components:
Polycythemia
B) Erythrocytes (red blood cells – RBCs)
( red blood cell number)
C) Leukocytes (white blood cells – WBCs)
• Only complete cell in blood (e.g., nucleus / organelles)
• Function in defense against disease
Polycythemia increases blood viscosity,
causing it to flow sluggishly
~ 4800 – 10,800 WBCs / l
• ONLY utilize blood for transport
Whole blood
EPO
Rolling
Polycythemia vera
(bone marrow cancer)
Aplastic anemia
(red marrow destruction)
Margination
Migration
Diapedesis
Artificial polycythemia
(blood doping)
Tight
adherence
Secondary polycythemia
(high altitude living)
Amoeboid
movement
“leaping across”
Inflamed endothelial cells sprout
cell-adhesion molecules (CAMs)
Carman, C.V., Journal of Cell Science. 2009;122:3025-3035
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
Blood Components:
C) Leukocytes (white blood cells – WBCs)
1) Neutrophils (50 – 70%)
C) Leukocytes (white blood cells – WBCs)
Categories of Leukocytes:
Categories of Leukocytes:
Granulocytes (contain granules)
Agranulocytes (lack granules)
2) Eosinophils (2 – 4%)
3) Basophils (< 1%)
• Small granules
• Large granules
• Large granules
(hydrolytic enzymes/defensins)
(lysosomes)
(histamines)
• Multi-lobed nucleus
• Engulfs bacteria / fungi
• Bi-lobed nucleus
• Kills parasitic worms
• U-shaped nucleus
• Vasodilator / attracts WBCs
1) Lymphocytes (15 – 45%)
• Large nucleus (spherical)
• Function in immunity
T lymphocytes
B lymphocytes
Lifespan = hours – decades
2) Monocytes (3 – 8%)
• Largest of WBCs
• U-shaped nucleus
• Function as macrophages
(differentiate in tissues)
Lifespan = hours – months
Lifespan = hours – days
3
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
C) Leukocytes (white blood cells – WBCs)
Hormones:
C) Leukocytes (white blood cells – WBCs)
Leukopoiesis (white blood cell formation):
Interleukins
Colony-stimulating factors
Lymphoid
stem cell
Excessive number of
agranulocytes
Leukemia:
Lymphocyte
• Uncontrolled proliferation of WBCs (cancerous)
Monocyte
Monoblast
Granules appear
Nuclei arc
Neutrophilic
myelocyte
Neutrophilic
band cell
Hemocytoblast
Epstein-Barr
virus
Pathophysiology:
migrate to
lymphoid tissue
Lymphoblast
(+)
Mononucleosis:
Blood Components:
• Named according to abnormal
cell line involved
Neutrophil
(stem cell)
Acute leukemia:
Chronic leukemia:
Derived from blast-type cells
Derived from later cell stages
• Rapid advancement
• Slow advancement
• Often observed in children
• Often observed in elderly
Lymphocytic leukemia
Basophilic
myelocyte
Myeloblast
Symptoms:
Basophilic
band cell
Myeloid
stem cell
Eosinophilic
myelocyte
Eosinophilic
band cell
Treatment:
• Anemia / bleeding problems
Basophil
• Irradiation
• Fever / weight-loss
• Chemotherapy
• Frequent infections
• Bone marrow transplant
Myelocytic leukemia
Eosinophil
Cardiovascular System – Blood
Cardiovascular System – Blood
Blood Components:
Hemostasis (“stoppage of bleeding”):
• Series of fast, localized reactions to halt blood loss
D) Platelets (thrombocytes)
• Cytoplasmic fragments (anucleate)
• Function in blood clotting (contain clotting chemicals)
Phase 1:
Phase 2:
Vascular spasm
Platelet plug formation
Vasoconstriction of damaged vessel
Temporarily seals vessel break
Thrombopoiesis (platelet formation):
Hormone:
Thrombopoietin
(+)
Myeloid stem cell
Hemocytoblast
(stem cell)
• ~ 150,000 – 400,000 / l
• Lifespan = ~ 10 days
(significantly reduces blood loss)
Repeat mitosis;
no cytokinesis
Megakaryoblast
Megakaryocyte
Platelets
Activated by:
1) Direct injury to smooth muscle
2) Chemical release (endothelial cells)
3) Nociceptors
(positive feedback loop)
Intact endothelial cells release nitric oxide
and prostacyclin which prevent platelet
aggregation in undamaged tissue
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.13
Cardiovascular System – Blood
Cardiovascular System – Blood
Hemostasis (“stoppage of bleeding”):
Hemostasis (“stoppage of bleeding”):
• Series of fast, localized reactions to halt blood loss
Platelet plug formation:
Step 1:
Formation of prothrombin
activator
Phase 3:
Rupture of vessel
von Willebrand factor:
Large plasma protein; links
platelets to collagen fibers
Attracts more
platelets
Collagen exposed
Coagulation (blood clotting)
Platelets swell and form
spiked processes
(+)
Platelets stick to collagen
Vascular spasms
Blood converted from liquid to gel
(3 – 6 minutes)
Platelets release contents
• Requires clotting factors (procoagulants)
Aspirin
Adenosine
diphosphate
(ADP)
Thromboxane
A2
Serotonin
Activation turns
clotting factors into
enzymes
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
4
Cardiovascular System – Blood
Cardiovascular System – Blood
Step 1:
Formation of prothrombin
activator
Hemostasis (“stoppage of bleeding”):
• Series of fast, localized reactions to halt blood loss
(all factors found within blood)
Anticoagulants:
Factors that inhibit clotting
Hemostasis (“stoppage of bleeding”):
(e.g., heparin)
• Series of fast, localized reactions to halt blood loss
(requires factor outside blood)
Step 2:
Formation of thrombin
Intrinsic pathway:
• triggered by negatively charged surfaces
• Inactivated by antithrombin III
(platelets / collagen / glass)
• Slow due to many intermediate steps
Step 3:
Formation of fibrin mesh
Extrinsic pathway:
• triggered by factor found in tissues under
the damaged endothelium (tissue factor)
• Rapid due to few intermediate steps
Severe trauma:
15 seconds
Both pathways cascade to activation
of Factor X which combines with Platelet
Factor 3 (PF3), Ca++, and Factor V to form
Prothrombin Activator
Activation turns
clotting factors into
enzymes
Factor XIII (fibrin stabilizing factor):
Cross-linking enzyme that binds fibrin
strands together
Found on surface
of platelets
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures17.14
Cardiovascular System – Blood
Cardiovascular System – Blood
= requires vitamin K
for synthesis
Hemostasis (“stoppage of bleeding”):
Hemostasis (“stoppage of bleeding”):
• Series of fast, localized reactions to halt blood loss
(2 days following damage)
Clot Retraction / Repair:
Fibrinolysis:
(30 – 60 minutes following damage)
• Process of removing clot once healing
has occurred
• Platelets contain actin / myosin fibers;
contract in manner of muscle fibers
(draws ruptured edges of blood
vessel closer together)
Plasmin:
Fibrin-digesting enzyme (‘clot buster’)
(incorporated
into clot)
Platelet-derived growth factor:
Released by platelets; stimulates smooth
muscle cells and fibroblasts to divide and
rebuild vessel wall
Plasminogen
Plasmin
tissue plasminogen
activator (tPA)
(released by
endothelial cells)
Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Table 17.3
Cardiovascular System – Blood
Cardiovascular System – Blood
Hemostasis (“stoppage of bleeding”):
Hemophilia:
Disorders of Hemostasis:
Thromboembolic Disorders
(undesirable clot formation)
Bleeding Disorders
(abnormal bleeding due to inability to clot)
(less severe)
Petechiae
Hemophilia C
Factor XI deficiency
Symptoms:
Hemophilia B
Factor IX deficiency
Thrombus:
A clot develops in an
unbroken blood vessel
Embolus:
A free-floating clot in
the bloodstream
Thrombocytopenia
Impaired Liver Function
• Deficiency in platelets
• Marrow destruction
• Vitamin K deficiency
• Cirrhosis / hepatitis
• Prolonged bleeding
Hemophilia A
Factor VIII deficiency
• Disabled / painful joints
77% of cases
(may lead to embolism)
Causes:
• Roughened endothelium (e.g., atherosclerosis)
• Slowly flowing blood
(e.g., airlines - economy class)
Hemophilia
• Missing clotting factor(s)
Treatment:
• Genetic (e.g., X-linked)
• Plasma transfusions
• Injection of clotting factor(s)
5