The Blood

A generalized collection ofhandouts and illustrations

to accompany lecture

By Noel Ways

HOMEOSTASIS

HYPOXIA

( - )

Contents:

Page 1 - TitalPage 2 - ContentsPage 3 - Erythrocyte MetabolismPage 4 - HematopoiesisPage 5 - EythropoiesisPage 6 - Erythropoiesis RegulationPage 7 - CO2 TransportPage 8 - Heme MetabolismPage 9 - Iron TransportPage 10 - Lymphocyte IntroductionPage 11 - Hemostasis

Page 2

22

P P

PP

PP

P

P

P PGlu

cose G

luco

se-6

-Pho

spha

te

Fruc

tose

-6-P

hosp

hate

Fruc

tose

-1,6

-Pho

spha

te

3-Ph

osph

ogly

cera

ldeh

yde

Dih

ydro

xyac

eton

ePh

osph

ate

1,3

Dip

hosp

hogl

ycer

ate

3-Ph

osph

ogly

cera

te

2-Ph

osph

ogly

cera

te

Phos

phoe

nol p

yruv

ate

2 2 2 2

ATPAD

P

ATPAD

P

NAD

+

NA

DH

Pyru

vate

2

ATP

ADP

ATP

ADP

ATP

ADP

ATP

ADP

ATPAD

P

ATPAD

P

NAD

+

NA

DH

Lact

ate

PP

Eryt

hroc

yte

Met

abol

ism

: Gly

coly

sis

Dur

ing

the

ejec

tion

stag

e of

ery

thro

poie

sis,

the

mito

-ch

ondr

ia a

re e

limin

ated

, and

with

them

, the

abi

lity

to d

o ce

llula

r res

pira

tion

(tra

nsiti

on s

tage

, kre

b’s

cycl

e, a

nd

elec

tron

tran

spor

t cha

in).

Ther

efor

e, th

e on

ly m

etab

olic

pat

hway

rem

aini

ng fo

r ATP

pr

oduc

tion

is th

at w

hich

occ

urs

in th

e cy

topl

asm

: gly

co-

lysi

s. A

lthou

gh A

TP p

rodu

ctio

n th

roug

h gl

ycol

ysis

is

mod

est,

the

net g

ain

of tw

o AT

P pe

r one

glu

cose

is

adeq

uate

for t

he re

quire

d m

etab

olic

act

ivity

of t

he

eryt

hroc

yte.

Due

to th

e ab

senc

e of

mito

chon

dria

, oxy

gen

is n

ot

requ

ired

nor c

an it

be

used

. Thi

s is

ben

e�ci

al a

s th

e er

ythr

ocyt

e do

es n

ot u

se it

s ca

rgo:

oxy

gen

and

can

deliv

er th

e go

ods

to th

e ce

lls th

at d

o re

quire

oxy

gen.

In th

is c

ase,

in o

rder

for g

lyco

lysi

s to

pro

ceed

ana

erob

i-ca

lly, N

AD

+ m

ust c

ontin

ue to

be

avai

labl

e to

pic

k up

el

ectr

ons

and

depo

sit t

hem

som

ewhe

re in

ord

er to

kee

p th

is a

naer

obic

pat

hway

goi

ng. T

here

fore

, NA

DH

will

be

oxid

ized

to N

AD

+ by

redu

cing

pyr

uvat

e to

lact

ate.

Eryt

hroc

yte

met

abol

ism

is a

naer

obic

. The

y do

not

use

th

e ox

ygen

that

they

car

ry.

Page

3

HemopoieticStem Cells

MyloidStem Cells

LymphoidStem Cells

Erythrocytes Thrombocytes Basophils Eosinophils Neutrophils Monocytes

Macrophages

B Lymphocytes(Humeral Immunity)

T Lymphocytes(Cellular Immunity)

Gas Transport & Hemostasis Nonspecific Host Immunity

Conferance ofImmunocompotence

in Bone Marrow

Conferance ofImmunocompotence

in Thymus Gland

SpecifcHost

Immunity

Plasma B CellsAntibodies

Memory B Cells

Helper T Cells

Cytotoxic T Cells

Regulator T Cells

Memory T Cells

HematopoiesisFlow Chart

Page 4

HemopoieticStem Cells

MyloidStem Cells

Committed Cell - Cell is committed bedi�erentiating into an erythrocyte

LymphoidStem Cells

LymphoidCell Lines

(B and T cells)MyloidCell Lines

(Basophils, eosinophils, etc.)

Hemopoietic (or Hematopoietic)Stem cells are Multipotent

Multipotent Stem Cells give rise toMany cell lines

Oligopotent Stem Cells give rise to aFew Cell lines

Unipotent Stem Cells give rise to onlyOne Cell line.

Multipotent

Oligopotent

Erythrocyte Development

Stage #1 - Ribosome Production (for protein synthesis, ie hemoglobin, enzyme systems, etc.)

Stage #2 - Hemoglobin Synthesis (as well as other proteins) Hemoglobin accumulates in the cell.

Stage #3 - Ejection Stage (Nucleus, mitochondria are ejected)

Mature Erythrocyte - Ejection stage results to collapse of cell, taking on a Biconcave shape. This increases the surface area for gas di�usion.

Loss of Mitochondria results is loss of ability to do cellular respiration.Respiration is therefore anaerobic. RBC will not use it’s cargo (oxygen)

Erythropoiesis

Reference: http://classes.midlandstech.com/carterp/Courses/bio211/chap17/Slide6.JPG

Page 5

ControlCenter

Efferent Pathway: Blood Stream(Erythropoietin ( ) Secreted)

a glycoprotein hormone

Afferent Pathway

(Blood by wayof its oxygen

carrying capacity)

HomeostasisRestored

(O2 Carrying Capacity of blood increases)

Effector(In Adult: sternum, ribs

vertebrae, pelvisand proximal ends ofhumerus and femur)

(Hematopoietic Stem Cellsin Red Bone Marrow

stimulated)

Erythropoiesisrate increase

Effect:(Erythrocyte Count

increases)

StressHYPOXIA

(Reduced O2in blood)

Regulation of Erythropoiesis

Time

Set Point Normal PhysiologicalRange for O2 Levels

Physiological Stress due to a decreased oxygen carrying capacity of blood may be caused by:

• Reduced O2 is atmosphere • Inadequate hemoglobin • Low red blood cell (erythrocyte) count • ETC . . .

( - )

Page 6

CO

2

CO

2

CO

2

Alv

eoli

of L

ungs

Eryt

hroc

yte

Eryt

hroc

yte

10%

D

isso

love

d in

Pla

sma

60%

30%

Atta

ched

to g

obin

as C

arba

min

ohem

oglo

bin

30%

Atta

ched

to g

lobi

nas

Car

bam

inoh

emog

lobi

n

10%

Dis

solo

ved

in P

lasm

a

CO

2 +

H2O

H2C

O3

H2C

O3

H

2O +

CO

2

H+ +

HC

O3-

HC

O3-

Cl-

Chl

orid

eSh

iftH

CO

3-C

l-C

hlor

ide

Shift

HC

O3- +

H+

Inte

rstit

ial T

issu

esge

nera

te C

O2.

whi

chis

tran

spor

ted

in th

e bl

ood

to lu

ngs.

CO

2 in

crea

selo

wer

s the

pH

(blo

od is

aci

difie

d)

CO

2 de

crea

se ra

ises

the

pH

(blo

od b

ecom

es m

ore

alka

line)

From

the

bloo

d, C

O2

diffu

ses i

nto

air s

pace

s of

the

lung

.

CO

2 Tra

nspo

rt in

Blo

od

Inte

rstit

ium

Page 7

Red Blood Celldamaged

HemoglobinReleased

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

Fe

FeFe

Fe

Fe

Fe

Fe

FeProtein Globinsbroken down intoamino acids

Amino Acidsreused for protein synthesisin body

HemeBiliverdinBilirubinBilirubin complexedwith albumin entersblood stream

Iron complexed with Transferrinis transferred through the bloodto other organs

The liver is the primary storageorgan of the bodyfor iron

In red bone marrow,iron will be incorporatedinto hemoglobin during hemopoiesis

Liver retrievesthe bilirubinand it is putinto the bile,and temporarilystored in thegall bladder

During digestionbile (with bilirubin)enters digestive tract.Bacterial activity creates“bilirubin derivatives” which color feces.

Some of these derivatives are absorbed intothe blood but willbe eliminated in theurine, giving in thecharacteristic yellow color

Macrophages inspleen and liver etc.injest hemoglobin

Hemoglobin Breakdown

Page 8

FeFeFe Fe

FeFe

Fe

Fe

FeFeFe

Fe

FeFe

Fe

FeFe

Iron does not normally exist in the body unaccompanied by a protein. Within cells Ferritin (and hemosiderin) are the intracellular storage proteins. As Ferritin is limited within intestinal cells, the intestine limits the amount of iron that can be absorbed. Once ferritin within intestinal cells is saturated, additional iron within intestinal lumen will be excreted.

Transport of iron within the blood is accompanied by a protein called Transferrin. Transferrin will carry the iron to organs such as the liver or spleen or to the red bone marrow for incorporation into hemoglobin. Once the transferrin-iron complex reaches its destination, the iron must then be complexed with ferritin at the new cell site.

IRON TRANSPORT

Iron stored in cells is complexed with Ferritin

Transferral of Iron within the blood occurs with a protein called Transferrin

Red BloodCell CountGoes Up. Iron incorporated into erythrocytes

Erythrocyte longevity is 80 - 120 days

Storage of Iron occurs in liver and spleen, complexed with Ferritin

FeFe

Fe

Fe

Excreted

Page 9

Fe Fe

Fe

Fe

Fe

Fe

LIVER

Spleen

Spleen processes cells and hemoglobin. Iron complexeswith Ferritin.

B

T

T

T

T

Tc

Tc

TcTc

B B

B

Bp

TcTc

Infection

Infection

Introduction to Lymphocytes

Page 10

Factor X Prothrombinase

Prothrombin Thrombin

FibrinogenFibrinogen

Fibrin

Fibrin

Common Pathway leads to polymerization of Fibrinogen into fibrin fibers. These fibrin fibers will be cross-linked to form a secure adhesive mesh that can effectively stop bleeding.

Hemostasis PlateletErythrocyte

EndotheliaCollagen

Interstitium

Platelet Plug - Exposed collagen due to endothe-lia damage allows for platelet adhesion, enlarge-ment, and aggregation. Platelets soon release serotonin and clotting factors.

Platelet-released clotting factors initiate a complex cascade of reactions culminating in Factor X activation and the, therefore, the “common pathway”.

Damaged tissues release “tissue factor,” which bypasses several reactions of the Intrinsic pathway prompting quick activation of the common pathway.

Synergist opera-tion of both path-ways results in both a quick and prolonged response that will efficiently stop blood flow in almost all cases.

IntrinsicPathway

ExtrinsicPathway

Page 11