Zhikal O. Khudhur/Assist lecturer_____________________________________________Hematology– 3rd Stage /1st Semester

zhikal.omer@tiu.edu.iq https://tiu.edu.iq/

2021 - 2022

TIU - Faculty of ScienceMedical Analysis Department

Lec. 4: Hemoglobin Distruction

Erythrocyte membrane

• RBC plasmalemma is trilaminar–

–

–

Outermost layer: glycolipids, glycoproteins

Central layer: cholesterol, phospholipids

Inner layer: cytoskeleton

– spectrin»

»

Composed of alpha & beta chains

Join to form a matrix which strengthens the

sheer force and controls biconcave shapemembrane against

• ankyrin

Importance of Hb within RBC

• Intra RBC environment is a little more acidicthan plasma for capable respiration

Hb is removed from metabolic pool, preventing its rapid turn over.

•

•

•

•

Half-Life for Hb in

Half-Life for Hb inHb chemical stateabsolutely.

RBC is months,plasma is only 3 hrs.

is required for O2 transport

• Each Saturated gram of Hb can carries 1.3 mloxygen

Destruction of erythrocytes

Cell decrease deformability in microcirculationassociated with;

is

1.

2.

3.

4.

increase in red cell rigidity

increase in blood viscosity,

impeded blood flow

cell fragmentation

The changes inMaintenance of

Normal internal

deformability depends on

cell geometry or biconcave shape

or hemoglobin fluidity Intrinsic

membrane deformability or visco-elastic properties

---------�"'.Agod. abnormal,

M<icropnagetn �preenor hver

or damagoderyttir ocytoi.

\ "']"�Heme

t

• •l r y throcytos

� E,ythropo1es1s

Red bonemarrow

enuubin excreted

Into ,ote$1tne a:. part ol btle

...

S.11 rubin convert

ad into pgmont<11

that ore pan 01

leces

HemoglobinMolecules of hemoglobin account for 95% of the proteinsin RBCs

Hemoglobin is a globular protein, formed from two pairs of

•

•

polypeptide subunits

– Each subunit contains a molecule of heme which reversibly binds an oxygen molecule

Damaged or dead RBCs are recycled by phagocytes•

Structure4 polypeptide

Subunits

Heme group

Porphyrin ring

Ferrous iron

Globin chain

2 Alpha Chains

2 Beta chains

of Hemoglobin

Heme has a variety of functions. As a cofactor

•

•

•

•

•

Oxygen transport in hemoglobin

Storage in myoglobin

A prosthetic group for cytochrome p450 enzymes

A reservoir of iron

Electron shuttle of enzymes in the electron transport chain

Cellular respiration

Signal transduction-heme regulates the antioxidantresponse to circadian rhythms, microRNA processing

Cellular differentiation and proliferation

•

•

•

Difference between oxygenation

and oxidation of Hemoglobin

• IRON(Fe +2) INFERROUS STATE

CARRIER OF OXYGEN

• IRON(Fe +3) IN FERRICSTATE

OXYGEN CARRYING CAPACITY IS LOST

• •

OXYGENATION OXIDATION

Functions of Hemoglobin

• Oxygen delivery to the tissues

• Reaction of Hb & oxygen

• Oxygenation not oxidation

• One Hb can bind to four O2 molecules

• Less than 0.01 sec required foroxygenation

• When oxygenated 2,3-DPG is pushed out

Normal Hemoglobin Function

When fully saturated, each gram ofhemoglobin binds 1.34 ml of oxygen.

The relation between oxygen tension and hemoglobin oxygen saturation is described by the oxygen-dissociation curve of hemoglobin.The characteristics of this curve are relatedpH, temperature, ionic strength, and

•

•

• to

concentration of phosphorylatedcompounds, especially 2,3-diphosphoglycerate (2,3-DPG).

Interstitial fluid

c o 2 - - - • c o , (dissolved In

plasma)

� B i n d s t oroteins( plasma p

HBO2 98.5 %O2 Dissolved in

Plasma 1.5%

WC0 C02 + H20 Slow H2C0 3 - HC0 3- +2

Tissue cell

tt.COa- HCOa-+Clrbonlc

CO2 in plasma 5-7%bicarbonate buffersystem 85% CO2 Dissolved in Plasma 10%

8nhydreseC02 -

C02 -lllll!l�-111111!! (C• rbamlno•

hlmoglobln)

Blood plasma02 (dissolved In

plasma)(a) Oxygen release and carbon dioxide pickup at the t issues

co2 •------..Alveolus Fused basement membranes• - - - - - - c o2 (d isso lved In

plasma)

HC01Reverse

C0 +--- - - - ""!""""!'- - - - - - C0 2 + H20 - H2C0 3 - HC0 3- + W

Slow

2

3

chloride

....,..---,- c l- shit !

Blood plasma02 (dissolved In

plasma)(b) Oxygen pickup and carbon dioxide release In the lungs

Hb-oxygen dissociation curve

is a curve thatplots theproportion ofhemoglobin inits saturated(oxygen-laden)form on thevertical axisagainst theprevailingoxygen tensionon the horizontalaxis

RBC life span and circulation

Replaced at a rate of approximately 3 million new•blood cells entering the circulation per second.

••

Replaced before they hemolyzeComponents of hemoglobin individually recycled– Heme stripped of iron and converted to biliverdin, then

bilirubin

Iron is recycled by being stored in phagocytes, or transported throughout the blood stream bound to transferrinRBC life span 120 days only, short because of the lack

•

•

of nuclei• RBC is soft colloid to change shape in various sized

vessels

Red

MACROPHAGE

Blood Cell Turnover1- - - .....;:i....�Fe2+

Amino acids

BONE

MARROW

RBCfonnation

transported in circulation by transferrln

BLOODPLASMA New RBCs

released Into circulation

- - - - 9 0% � 1:\-_.....i,""1Old and I �

10%

L _ _ _ J

Macrophages in spleen, liver, bone marrow

damagedRBCs Hem.o.l,ysi

s

��

.- - - - - - - - - - - -1-..... Bilirubin

, - - - - - ----1 Bilirubin-derivedproductsLIVER

Excreted Absorbed intoEliminated

in urinein bile'r:;:::� ==::::::±t-h.e.._c_r::u:l::io:n:::

_.ll.::::::::::: Bilirubin-derived 1--. l urobilinsSMALL

INTESTINE products Stercobilins

Eliminatedin fecesLARGE

INTESTINE

Erythropoiesis

Erythropoietin MechanismStart

burst forming unit-erythroid

Colony Forming Unit-erythroid

Erythropoietin receptor

Stimulus:

Hypoxia due to

decreased RBC

count,decreased availability of O2 to

blood,

increased tissue demands for O2