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Cell

O2

CO2

Nutrients

Waste

O2 / Energy

CO2 / Waste

CO2 / Waste

External environment:

O2 / Nutrients

Source

Sink

TOO MUCH

TIME

Transport System of the Body:

100 m 1 s

1 mm 100 s

1 cm 10000 s distance = time2

Cell

O2

CO2

Nutrients

Waste

O2 / Energy

CO2 / Waste

CO2 / Waste

External environment:

O2 / Nutrients

Transport System of the Body:

Source

Sink

Diffusion

Bulk flow

(pressure)

2

Cardiovascular System:

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”):

Cardiovascular System – Blood

1) Distribution

• Delivers oxygen / nutrients

• Carries away metabolic wastes

• Transports hormones

2) Regulation

• Maintains body temperature / pH

• Maintains fluid volumes

3) Protection

• Prevents blood loss (e.g., clot formation)

Blood:

Bloodletting a

common medical

treatment in the

Middle Ages

• Prevents infection (e.g., antibodies)

3

Erythrocytes

(~ 45%)

• Erythrocytes (RBC’s)

Buffy Coat

(~ 1%)

• Leukocytes (WBC’s)

• Platelets

Formed

elements

1) Formed Elements (living cells)

Plasma

2) Plasma

• Non-cellular fluid matrix (dissolved proteins)

Hematocrit:

% of whole blood containing

formed elements

Males ~ 47%

Females ~ 42%


Blood Components:

A) Plasma

• Distributes materials / heat

Serum:

Plasma minus

clotting proteins

C) Other solutes (~ 2%; >100 different solutes present; Table 17.1)

Blood Components:


Composition:

A) Water (~ 90%)

B) Protein (~ 8%)

(Primarily produced

by liver)

Albumin

• Osmotic pressure

• Transport

Globulins

• Transport ( / )

• Antibodies ()

Fibrinogen

• Clotting protein

• Electrolytes (e.g., sodium)

• Respiratory gases (e.g., O2)

(precisely maintained)

60% 36% 4%

• Organic nutrients (e.g., glucose)

• Nitrogenous waste (e.g., urea)

4

Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Figures 17.3 / 17.14

• Small (~ 7 m); biconcave (“certs”)

Heme (O2-binding pigment w/ iron) + Globin (protein)

4 globins / hemoglobin

(2 chains; 2 chains)

= 4 molecules O2

B) Erythrocytes (red blood cells – RBCs)

Blood Components:


Shape maintained by network

of proteins (e.g., spectrin)

• Contain hemoglobin (O2 / CO2 transport protein)

Why maintain hemoglobin

in erythrocytes?

1) Leakage through capillary walls

• Anucleate (lacking nucleus); few organelles

2) Viscosity / osmotic pressure issues

250 million / cell

Structure complements function

1) Small size and shape equates to large

surface area / volume

Rapid respiratory gas loading / unloading

2) 97% of cell volume is hemoglobin (~ 250 million hemoglobin)

Mass transport of respiratory gases

3) Lack mitochondria (don’t burn oxygen)

Efficient transport of respiratory gases


Blood Components:


5

Erythropoiesis (red blood cell formation):

• ~ 2 million RBCs produced per second

• Formation occurs in red bone marrow

Sternum

Vertebra

Ribs

Axial skeleton

Age (years)

Low

High

Young Old

Femur

Tibia

Long bones


Blood Components:


Hemocytoblast (stem cell)

Myeloid stem cell Erythroblast

(ribosome factory)

Normoblast

(nucleus

ejected)

Reticulocyte

(enters blood stream)

Erythrocyte



Blood Components:


1 – 2 % of RBCs

Reticulocyte Count:

Provide rough index of RBC

formation rate

Entire process takes

~ 15 days

6

Produced by the kidney

and liver

(~ 85%) (~ 15%)

Normal Blood Oxygen Level

Hypoxia

1) RBC loss

2) hemoglobin

3) Low O2

Reduced O2

level in blood

Kidney releases

erythropoietin

Erythropoietin stimulates

bone marrow

RBCs mature

more rapidly

Increased O2

level in blood

(-)



Blood Components:


• Regulated hormonally by erythropoietin


Blood Components:


• Dietary requirements must be met for normal RBC formation

Iron: (hemoglobin synthesis)

Vitamin B12 and folic acid

necessary for proper DNA synthesis

• Stored in liver & spleen in protein-iron

complexes ferritin and hemosiderin

Ferritin (24 protein subunits)

• Transported in blood bound to transferrin

Transferrin (Glycoprotein; 2 binding sites)


Free iron ions toxic!

• Acts as a catalyst for

the formation of

free radicals

//upload.wikimedia.org/wikipedia/commons/6/64/Protein_TF_PDB_1a8e.png

//upload.wikimedia.org/wikipedia/commons/e/ec/Cobalamin.png

//upload.wikimedia.org/wikipedia/commons/8/85/Folicacid2.png

7


Blood Components:


Destruction of Erythrocytes

• “Old” RBCs engulfed by macrophages

in spleen / liver

• Lose flexibility

Jaundice:

Yellowing of skin due to

bilirubin deposition

• Iron salvages; stored for re-use

• Heme group degraded to bilirubin

Bilirubin (captured by liver;

released via gallbladder) (yellow pigment)

Urobilinogen (metabolized in

large Intestine)

Stercobilin (brown pigment) (exits in feces)

• Globins recycled to amino acids

Pathophysiology:

Anemia ( oxygen carrying capacity of blood)


Blood Components:


Decreased

number of RBCs

Decreased

hemoglobin content

Abnormal

hemoglobin

Hemorrhagic anemia

(blood loss)

Hemolytic anemia

(RBC rupture)

Aplastic anemia

(red marrow destruction)

Iron-deficiency anemia

(inadequate intake of iron)

Pernicious anemia

(deficiency of vitamin B12)

Microcytes

Macrocytes

Sickle-cell anemia

(genetic mutation – abnormal globin) Thalassemias

(genetic mutation – missing globin)

http://en.wikipedia.org/wiki/File:Jaundice08.jpg

8

Pathophysiology:

Polycythemia ( red blood cell number)


Blood Components:


EPO Whole blood

Polycythemia increases blood viscosity,

causing it to flow sluggishly

Polycythemia vera

(bone marrow cancer)

Secondary polycythemia

(high altitude living)

Artificial polycythemia

(blood doping)

C) Leukocytes (white blood cells – WBCs)

Blood Components:


• Only complete cell in blood (e.g., nucleus / organelles)

• ONLY utilize blood for transport

• Function in defense against disease ~ 4800 – 10,800 WBCs / l

Carman, C.V., Journal of Cell Science. 2009;122:3025-3035

Rolling

Inflamed endothelial cells sprout

cell-adhesion molecules (CAMs)

Margination Migration

Tight

adherence

Diapedesis

“leaping across”

Amoeboid

movement

9


Blood Components:


Categories of Leukocytes:

1) Neutrophils (50 – 70%)

• Multi-lobed nucleus

• Engulfs bacteria / fungi

• Small granules

(hydrolytic enzymes/defensins)

Granulocytes (contain granules)

2) Eosinophils (2 – 4%)

• Bi-lobed nucleus

• Kills parasitic worms

• Large granules

(lysosomes)

3) Basophils (< 1%)

• Large granules

(histamines)

• U-shaped nucleus

• Vasodilator / attracts WBCs

Lifespan = hours – days


Blood Components:


Categories of Leukocytes:

1) Lymphocytes (15 – 45%)

T lymphocytes

B lymphocytes

• Large nucleus (spherical)

• Function in immunity

Agranulocytes (lack granules)

2) Monocytes (3 – 8%)

• U-shaped nucleus

• Largest of WBCs

• Function as macrophages

(differentiate in tissues)

Lifespan = hours – decades Lifespan = hours – months

10


Blood Components:


Leukopoiesis (white blood cell formation):

Eosinophilic

myelocyte Eosinophilic

band cell


Myeloid

stem cell

Lymphoid

stem cell

Myeloblast

Neutrophil

Neutrophilic

myelocyte

Basophil

Eosinophil

Neutrophilic

band cell

Basophilic

myelocyte Basophilic

band cell

Granules appear Nuclei arc

Lymphoblast Lymphocyte

Monoblast Monocyte

Hormones:

Interleukins

Colony-stimulating factors

(+)

migrate to

lymphoid tissue

Blood Components:



Pathophysiology:

Leukemia:

• Uncontrolled proliferation of WBCs (cancerous)

• Named according to abnormal

cell line involved

Lymphocytic leukemia

Myelocytic leukemia

Acute leukemia:

Derived from blast-type cells

• Rapid advancement

• Often observed in children

Chronic leukemia:

Derived from later cell stages

• Slow advancement

• Often observed in elderly

Symptoms:

• Anemia / bleeding problems

• Fever / weight-loss

• Frequent infections

Treatment:

• Irradiation

• Chemotherapy

• Bone marrow transplant

Mononucleosis:

Excessive number of

agranulocytes

Epstein-Barr

virus

11

D) Platelets (thrombocytes)

Blood Components:


• Cytoplasmic fragments (anucleate)

• Function in blood clotting (contain clotting chemicals)

• ~ 150,000 – 400,000 / l


Myeloid stem cell

Megakaryoblast Megakaryocyte Platelets

Hormone:

Thrombopoietin

Thrombopoiesis (platelet formation):

• Lifespan = ~ 10 days

(+)

Repeat mitosis;

no cytokinesis

Hemostasis (“stoppage of bleeding”):


• Series of fast, localized reactions to halt blood loss

Phase 1:

Vascular spasm

Activated by:

1) Direct injury to smooth muscle

2) Chemical release (endothelial cells)

3) Nociceptors

Vasoconstriction of damaged vessel

(significantly reduces blood loss)

Phase 2:

Platelet plug formation

Temporarily seals vessel break

(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

12



Rupture of vessel

Platelet plug formation:

Collagen exposed

Platelets stick to collagen

von Willebrand factor:

Large plasma protein; links

platelets to collagen fibers Platelets swell and form

spiked processes

Platelets release contents

Adenosine

diphosphate (ADP)

Attracts more

platelets

(+)

Serotonin

Vascular spasms

Thromboxane

A2

Aspirin




Phase 3:

Coagulation (blood clotting)


Blood converted from liquid to gel

(3 – 6 minutes)

• Requires clotting factors (procoagulants) Activation turns

clotting factors into

enzymes

Step 1:

Formation of prothrombin

activator

13





Activation turns

clotting factors into

enzymes

Step 1:

Formation of prothrombin

activator

(all factors found within blood) (requires factor outside blood)

Intrinsic pathway:

• triggered by negatively charged surfaces

(platelets / collagen / glass)

• Slow due to many intermediate steps

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

Found on surface

of platelets





Step 2:

Formation of thrombin

Step 3:

Formation of fibrin mesh

Factor XIII (fibrin stabilizing factor):

Cross-linking enzyme that binds fibrin

strands together

Anticoagulants:

Factors that inhibit clotting (e.g., heparin)

• Inactivated by antithrombin III

14



Marieb & Hoehn (Human Anatomy and Physiology, 8th ed.) – Table 17.3

= requires vitamin K

for synthesis




Clot Retraction / Repair:

(30 – 60 minutes following damage)

• Platelets contain actin / myosin fibers;

contract in manner of muscle fibers

(draws ruptured edges of blood

vessel closer together)

Platelet-derived growth factor:

Released by platelets; stimulates smooth

muscle cells and fibroblasts to divide and

rebuild vessel wall

• Process of removing clot once healing

has occurred

Plasmin:

Fibrin-digesting enzyme (‘clot buster’)

Fibrinolysis:

Plasminogen Plasmin

(incorporated

into clot)

tissue plasminogen

activator (tPA)

(released by

endothelial cells)

(2 days following damage)

//upload.wikimedia.org/wikipedia/commons/6/6d/1PDG_Platelet-DerivedGrowthFactorBb.png

15


Thromboembolic Disorders

(undesirable clot formation)


Disorders of Hemostasis:

Thrombus:

A clot develops in an

unbroken blood vessel

Embolus:

A free-floating clot in

the bloodstream

(may lead to embolism)

Causes:

• Roughened endothelium (e.g., atherosclerosis)

• Slowly flowing blood (e.g., airlines - economy class)

Bleeding Disorders

(abnormal bleeding due to inability to clot)

Thrombocytopenia

• Deficiency in platelets

• Marrow destruction

Impaired Liver Function

• Vitamin K deficiency

• Cirrhosis / hepatitis

Petechiae

Hemophilia

• Missing clotting factor(s)

• Genetic (e.g., X-linked)

Hemophilia:

Hemophilia A

Factor VIII deficiency

77% of cases

Hemophilia B

Factor IX deficiency

Hemophilia C

Factor XI deficiency

(less severe)


Symptoms:

• Prolonged bleeding

• Disabled / painful joints

Treatment:

• Plasma transfusions

• Injection of clotting factor(s)

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