BiochemPpt - Hema RBC - 2013

7/31/2019 BiochemPpt - Hema RBC - 2013

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BLOOD CHEMISTRY

General Properties & RBC

Lecturer:Maria Milagros U. Magat, MD, MEM,FPPS,FPAPP


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BLOOD CHEMISTRY

Total blood volume: 5 6 liters (6 8% totalBW)

Color arterial bright crimson

venous dark red

pH = 7.35 7.45

Sp. Gr.= 1.035

1.075


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Blood components

a. fluid/ liquid portion plasma (55 60%)1. Water 90%2. Solutes 10%

a) proteins - 7% (albumin, globulin, fibrinogen)b) inorganic salts - 0.9%c) organic components 2.1%

** plasma = WB

formed elementsserum = WB (formed elements + clotting factors)


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1. Albumin2. Globulin3. Fibrinogen

** synthesis:

albumin & fibrinogen liver cellsglobulin

liver cells 80%plasma cells 20%

Types of plasma proteins


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1. Osmotic effect1 gm/dl = 5.54 mm Hg OP 18 ml fluid

2. Distribution & transport

3. Blood buffers

4. Nutritive effects

Albumin - functions


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b. formed elements (40

45%)

1. RBC or erythrocytes2. WBC or leukocytes

3. Platelets

Blood components


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RBC

Non-nucleatedNo mitochondriaDiameter = 6- 9 mThickness 1 u center, 2 2.5 m periphery

RBC count

4.5

5 million / mm3Life span 90 120 days


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RBC

Composition:a. water 60%b. solid 40%

1) hemoglobin - *main function2) other proteins albuminoid, stromatin,elinin, hemocuprein

3) lipids cholestrol, phosphatidyl choline,

phosphatidyl ethanolamine


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RBC membrane


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RBC

Shape : biconcave disc1. Attain maximum membrane SA2. Enable RBC to undergo changes in shape


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RBC

Normal erythropoeitic tissues:

bone marrow pelvis, spine, ribs, scapula,proximal ends of femur & humerus

*control of RBC production: erythropoietin (kidneys)

*nutritional requirements


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Fe deficiency anemia


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RBC

Blood group substances

-isoagglutinins or antigens

surface-responsible for different blood types of individuals

Bloodtype

Antigen Antibody

A A Anti B

B B Anti A

AB AB -

O - Anti - A

Anti - B


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Blood groups


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RBC

Metabolism of glucose

Embden Meyerhoff pathway( anaerobic glycosis) 90%

Hexose monophosphate shunt - 10%


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RBC : Protective features

6. Glutathione

peroxidase

2 GSH + R-O-OH

GSSG + H2O + ROH7. Fenton rxn Fe2+ + H2O2 Fe

3+

+ OH . + OH -

8. Haber

Weiss Rxn O2 - + H2O2 O2 +OH . + OH-

9. Glucose-6-PO4dehydrogenase (G6PD)

G6P + NADP6phosphogluconate +NADPH + H+

10. Glutathionereductase

GSSG + NADPH + H+

2GSH + NADP


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hemoglobin

Heme + globin


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globin


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Globin- tetramer 4 polypeptide chains

-Variants: Embryonal

Form Chaincomponent

HbGower1 z2e2

HbF a2g2

Hb- Gower2 a2e2Hb-Portland

z2g2


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Formation of globin chain variants


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Adult hemoglobin

form Chaincomponent

%

HbA a2b2 90 97%

HbA2 a2d2 2 5%

HbF a2g2 < 2%

HbA1c a2b2-glucose

3-9%


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myoglobin


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I. Abnormal hemoglobinA. Altered combination of normal globin chains

1. a thallasemia defective a chain synthesisforming homotetramers (g, b)- HbH (g4 or b4)

2. b thallasemia defective b chain synthesisHbF (a2g2), HbA2 (a2d2)

General Types of RBC Abnormalities


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B. Altered sequence of amino acids

1. HbS -Sickle cell anemia- mutant b globinchain (bS); a2b2; position 6 :valine(glutamic acid)

2. HbC

lysine

3. Hb SC

General Types of RBC Abnormalities


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Sickled RBC


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val 6

Sickled rbc


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a

Oxy A Deoxy A Oxy S Deoxy S

Sickle Cell Anemia: sticky patch formation

b

a b


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RBC membrane


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heme


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COOH

CH2CH2C=O

H-C-NH2H

Heme biosynthesis: PBG formation

COOHCH2CH2C

CH

COOH

CH2CH2C=O

H-C-NH2H

COOHCH2C

CN

CH2 H

NH2

H m bi s nth sis:


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COOHCH2C

CN

CH2 HNH2

COOH

CH2CH2C

CH

Heme biosynthesis:uropophyrinogen formation

A P AC

CNH

PC

CH

CH2

H2C

HN

C

C

C

C

CH2

HNC

C

C

C

CH2

P A P A

A ______P


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A P

A

P

P A

P

A

A P

A

P

P A

A

P

M P

M

P

P M

P

M

M P

M

P

P M

M

P

Heme biosynthesis: coproporphyrinogen formation

IIV II

III

4CO2I

IV II

III

I

IV II

III

IIV II

III


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M P

M

P

P M

M

P

I

IV IIIII

Heme biosynthesis: Protoporphyrinogen IX formation

M

M

P M

M

P

P

V

P

V


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Heme biosynthesis: Heme formation

M

M

P M

M

P

V

VV

P

N

HNH HNHN

M

M

P M

M

P

V

VV

P

N

HN N

HN

3H2

Fe2+


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reaction enzyme product

1. condensation ALA synthase ALA

2. condensation ALA dehydratase PBG

3. condensation HMB synthase HMB

4. cyclization Uroporphyrinogen IIIsynthase

Uroporphy-

rinogen III

5. decarboxylation Uroporphyrinogen decaboxylase CoproporphyrinogenIII

6.Decarboxylation &oxidation

Coproporphyrinogen oxidase ProtoporphyrinogenIII

7. oxidation Protoporphyrinogen oxidase Protoporphyrin III

8. Fe 2+

incorporated

ferrochelatase heme

Heme biosynthesis: Heme formation


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- RBC and liver

RBC 85%

Rate limiting steps in the pathways1. Ferrochelatase

2. PBG deaminase3. transferrin

Heme biosynthesis


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> 80% heme formed

Hgb

> 10% - myoglobin

5% - cytochrome & other heme proteins

Heme biosynthesis


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Causes of major s/sx in porphyria:DNA mutations

Abnormalities of enzymes in heme biosynthesis

Accumulated heme

&/or heme precursors

Neuropsychiatric s/sx

Accumulation of

porphyrinogens in skin& tissues

Spontaneous oxidation

of porphyrinogens toporphyrins

photosensitivity


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hemoglobinglobin

a.a.pool

heme FeHeme oxygenaseO2, NADPH

biliverdin

Bilirubin (unconjugated)

Bilirubin diglucoronide

glucuronosyltransferase

urobilinogen

urobilin

urine

stercobilinogen

stercobilin

feces

Fate of hemoglobin &heme degradation

transferrin Fe pool

newHgb

mesobilirubin

Ligandin

Protein Y

MRP-2
http://bilirubin.ppt/http://bilirubin.ppt/http://bilirubin.ppt/


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condition B1B2 Urineurobilinogen

Urinebilirubin

Fecalurobilinogen

Hemolyticanemia

B1 (-)

hepatitis B1B2 * *

Obstructivejaundice

B2 (-) (+) (-)/(+)

Neonataljaundice

B1 (-) (+) (-)

Lab. data of pts w/ jaundice of varied causes:


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BiochemPpt - Hema RBC - 2013