Blood

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3 Major Functions

Distribution:

Oxygen

Nutrients

Hormones

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3 Major Functions

Maintaining:

Body  temps

Normal pH

Fluid volume

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3 Major Functions

Protection:

Immune protection from infection

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Blood Components

Composed of:

erythrocytes

Leukocytes and platelets

Plasma

The % of erythrocytes in blood volume is the hematocrit.

hematocrit is an indirect measurement of the O2-carrying capacity of the blood.

More red blood cells mean more O2 carried by the same volume of blood.

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Components: Plasma

Blood plasma consists of mostly water (90%), and solutes including nutrients, gases, hormones, wastes, products of cell activity, ions, and proteins

(p. 636; Table 17.1).

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Components: Plasma

Plasma Proteins:

account for 8% of plasma solutes, mostly albumin, which function as carriers (p. 636).

Most produced by the liver

Are not used as fuels or metabolic nutrients by cells

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Components: Plasma

Plasma Proteins: Albumin

About 60% of plasma proteins consists of Albumin

It functions as

a carrier to transfer  molecules through circulation

Buffer

Plasma osmotic pressure

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Formed Elements

The cellular portion of blood produced by bone marrow

Consists of erythrocytes, leukocytes, and platelets

Most blood cells do not divide, they are continuously renewed by division of cells in red bone marrow

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Erythrocytes

are small cells

biconcave in shape.

lack nuclei and most organelles

contain mostly hemoglobin.

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Hemoglobin (Hb)

Hemoglobin is an oxygen-binding pigment that is responsible for the transport of most of the oxygen in the blood.

Adult hemoglobin is made up of the protein globin bound to the red heme pigment.

Globins consist of four polypeptide chains, 2 α and 2 β subunits.

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Hemoglobin (Hb)

Each subunit binds

to 1 heme group.

The heme group has

a ferrous ion (Fe2+ )

that will bind a gas molecule

Therefore each

hemoglobin molecule has

4 heme groups that

can bind 4 O2,

H+ or  CO molecules

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Heme

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is a square planar molecule

made of 4 pyrrole groups

in the middle of this ‘net’ is an iron atom, Fe+2 state called ferrous iron

Fe+2 has 6 available bonds it can form

the nitrogens of the pyrrole rings form 4 covalent bonds with the Fe

the 5th bond is formed with a histadine amino acid called the proximal histadine (called F8)

the 6th position is unbound: oxygen, CO can bind here

bound oxygen is stabilized by a distal histadine (E7)

Heme

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Heme

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Heme

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Myoglobin (Mb)

Is similar to Hb

Is made of a singular subunit

It has a heme group  that

binds oxygen molecules (O2)

O2 binds to the Fe+2 atom in the center of the heme group

It is found in striated muscle cells

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Hemoglobin (Hb) O2 Binding

The oxygen molecules bind cooperatively,

which means that when the first O2

binds, this causes a conformational

change in Hb by breaking salt bridges

b/t the subunits.

This causes the subunits to move

further away from each other, making it

easier for the second subunit to bind O2,

making  it easier for the third subunit to

bind O2, finally the fourth subunit

binds O2 easiest.

Oxygenated Hb = HbO2(red)

Deoxygenated Hb= DeoxyHb (blue)

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Hemoglobin (Hb) O2 Binding

Cooperative binding

also influences bond strength

b/t O2 and the heme such that

the first O2 binds weakly,

but induces a conformational

change  that causes the

second to bind more tightly,

and so on so that the fourth

oxygen is bound several

hundred times more strongly

than the first.

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Hb Cooperative Binding

Oxygen binding changes the confirmation of the hemoglobin that facilitates the binding of other oxygen molecules.

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Hemoglobin (Hb)

a high partial pressure of

oxygen is required to bind

the first oxygen

Therefore oxygen loading

occurs in the lungs, where it

there is more oxygen

but not in the oxygen-poor

tissues elsewhere, where it

needs to be released.

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Myoglobin O2 binding

Only has one subunit

Only has one O2 binding site

Can bind only 1 O2 molecule

O2 binding is NOT cooperative

Binds O2 tighter than Hb, ie. has a higher affinity for O2 than Hb

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Mb O2 binding

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Mb O2 binding

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When O2 binds to the Fe+2, the Fe+2

becomes Fe+3

Fe+3 is smaller than Fe+2

This pulls the O2 into the pocket and

the O2 is stabilized by the distal histidine

E7

Making the bond b/t O2 and Mb heme

stable and therefore strong

Hb vs Mb O2 binding

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Hemoglobin (Hb)

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2, 3 BPG and Hb O2 loading

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Hemoglobin (Hb)

DeoxyHb blood travels to the lungs

2. O2 diffuses from the air sacs into the blood and binds to the Ferrous iron of the hemes

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Hemoglobin (Hb)

3- HbO2 enters the heart

4- HbO2 blood is pumped

out to the rest of the body

via arteries

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Hemoglobin (Hb)

5-When the HbO2 reaches the  tissues the pO2 is

low, as well as the pH (≈7.2), which facilitates the release of bound O2 .

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Gas Exchange in Tissues

Metabolizing cells produce CO2 which diffuses into the blood and enters the circulating red blood cells (RBCs).

Within RBCs the CO2 is rapidly converted to

carbonic acid through the action of the RBC enzyme

carbonic anhydrase as shown in the equation 1 below:

(Eq 1) CO2 + H2O ——> H2CO3 ——> H+ +  HCO3–

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Gas Exchange in Tissues

(Eq 2) CO2 + H2O ——> H2CO3 ——> H+ + HCO3–

The bicarbonate ion produced in this dissociation reaction diffuses out of the RBC and is carried in the blood to the lungs. (equation 2)

This effective CO2 transport process accounts for the transportation of approximately 80% of the CO2 produced in metabolizing cells is transported to the lungs in this way.

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Gas Exchange in Tissues

About 15-20 % of CO2 is transported to the lungs bound to N-terminal amino groups of the DeoxyHb.

This reaction, equation 3, forms what is called carbamino-hemoglobin.

this reaction also produces H+, thereby lowering the pH in tissues where the CO2 concentration is high.

(Eq 3) CO2 + Hb-NH2 <——> H+ + Hb-NH-COO–

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Gas Exchange in Tissues

(Eq 3) CO2 + Hb-NH2 <——> H+ + Hb-NH-COO–

The formation of H+ leads to release of the bound O2 to the surrounding tissues. (equation 3)

        (Eq 4) H+  + HbO2 - -> HbH + O2

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Gas Exchange in Tissues

(Eq 5) DeoxyHb + Ox - -> HbO2 + H+  (in lungs)

Within the lungs (Eq 5), the high O2 content results in O2 binding to hemoglobin with the concomitant release of H+.

The released protons then promote the dissociation of the carbamino to form CO2 which is then released with expiration. (equation 3, reverse)

(Eq 3) CO2 + Hb-NH2 <——> H+ + Hb-NH-COO–

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Gas Exchange in Tissues

These effects of hydrogen ion concentration are responsible for Bohr effect

increases in hydrogen ion concentration decrease the amount of oxygen bound by hemoglobin at any oxygen concentration (partial pressure).

Coupled to the diffusion of bicarbonate out of RBCs in the tissues there Cl- ion is moved into the RBCs to maintain electrical neutrality.

This is the role of Cl- and is referred to as the chloride shift.

In this way, Cl– plays an important role in bicarbonate production and diffusion and thus also negatively influences O2 binding to hemoglobin.

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Bohr Effect

1-CO2 enters RBC

2- HCO3- formation

3-HCO3 and Cl-

are switched

 3a-(Chloride Shift)

4- H+ binds to Hb

forming HbH+

5- Release of O2 due

to binding of H+

6- O2 enters tissue

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1

2

3

4

5

6

3a

Bohr Effect

An increasing concentration of H+ and/or CO2 will decrease the affinity of Hb for oxygen.

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Bohr Effect

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Effect of pH on O2 Hb binding

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Effect of temp on O2 Hb binding

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Factors Effecting Hb O2 binding

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Fetal Hb (HbF)

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HbF vs HbA

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Hematopoiesis

Hematopoiesis- (blood cell formation) occurs in the red bone marrow.

Erythropoiesis, (formation of erythrocytes) begins when a myeloid stem cell is transformed to a proerythroblast, which develops into mature erythrocytes.

Erythrocyte production is controlled by the hormone erythropoietin (EPO).

Dietary requirements for erythrocyte formation include iron, vitamin B12, and folic acid, as well as proteins, lipids, and carbohydrates.

Blood cells have a short life span due to the lack of nuclei and organelles; destruction of dead or dying blood cells is accomplished by macrophages.

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Erythropoiesis

Stages of Development

1- Proerythroblast:

The first erythrocyte precursor

It has a large nucleus with free

ribosomes in the cytoplasm

giving the cytoplasm

a basophilic appearance.

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Erythropoiesis

Stages of Development

2- Basophilic erythroblasts

form next  produce many ribosomes

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Erythropoiesis

Stages of Development

3- Erythroblasts

form next

Hb is formed

Fe is accumulated

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Erythropoiesis

Stages of Development

4-Normoblasts

form next

color changes to pink

due to Hb formation

eventually the nucleus is  ejected 🡪 biconcave shape

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Erythropoiesis

Stages of Development

5-Reticulocytes

form next

filled with Hb

enter bloodstream

after 2 days of release, the ribosomes degrade

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Hormonal Control of Erythropoiesis

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Hormonal Control of Erythropoiesis

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RBC Fate

1- RBC fromation in bm

2- RBCs in bloodstream

3- Amino acids are used

to make proteins

4- Aged RBCs are

phagocytized in the liver

and spleen

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RBC Fate

5- Heme components

are recylced:

a- Iron is transferred in

the blood by the protein

transferrin and stored

in the liver  by the

protein ferritin

b- Heme is converted into

bilrubin and excreted as

part of bile in the liver

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Sickle Cell

A point mutation in

which Val replaces

a Glu in the β chain

of the Hb globin.

This causes the  β chains

to stick together under

low [O2] thus collapsing

the biconcave shape

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Sickle Cell

The sickled cells are

rigid and rupture easily

They also block blood

flow in the vessels

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Sickle Cell

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Valine

Glutamine