04 57 Blood Proteins Lavers

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Blood Proteins

Lecture 57Baynes & Dominiczak, Chapter 3 and 4

Gene C. Lavers, Ph.D.

gene.lavers@ nyu.edu

Copyright 1999-2004 by Gene C. Lavers

No part of this presentation may be reproduced by any mechanical, photographic, or electronic process, or in

the form of a phonographic recording, nor may it be stored in a retrieval system, transmitted, or otherwisecopied for public or private use, without written permission from the publisher.


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Copyright 1999-2004 by Gene C.Lavers

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Fluid Communication and Transport Blood CompositionUnicellular organisms Introduction

Unicellular organisms

(( cell )) media

obtain food and dispose of waste products directly withthe aqueous media in which the organisms exist.

media can change, e.g., depletion of food or accumulation

of waste or other substances. intracellular fluid maintenance of the proper composition

if fails, then the organism ceases to function.


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Fluid Communication and Transport Blood CompositionMulticellular organisms Introduction

direct exchange direct exchange

(( cell )) interstitial fluid (( blood ))indirect exchange

obtain food and dispose of waste products directly by

diffusion with a bathing aqueous media, i.e., the interstitialfluid.

interstitial fluid (media) is depleted of essential substancesand accumulates cellular waste or other substances.

circulating blood within capillary walls replaces essential

substances and removes accumulated waste therebymaintaining the interstitial fluid composition within properlimits (by diffusion).

intracellular fluid maintenance of the proper compositionsucceeds, and the tissue cells continue to function.


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Maintenance of Blood Composition Blood CompositionMechanisms

Blood is maintained within physiological limits byspecial mechanisms:

Provide essential substances Gastrointestinal system: nutrient food

Lungs: O2

Remove waste products Kidneys: urea, creatinine, NH3, etc. Lungs: CO2 Intestines: feces (e.g.,stercobilin)

Skin: sweat (salts and urea) Provide blood cells (formed elements) from bone marrow Proteins from Liver (e.g., clotting factors) Hormones from pancreas, adrenals, etc.


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General Functions Blood CompositionTransport

1.Food transport- absorbed digestion products from theintestines products move to the tissues for utilization.

2.Waste transport-waste products (urea, urate, creatinine

etc.) pass into blood then to kidneys and other organs forelimination.

3.Gaseous transport- O2via oxyhemoglobin from the lungs totissues for metabolic oxidation and energy production. CO2from cellular oxidation is carried from tissues by blood tolungs for exhilation.

4. Hormone transport- pituitary, thyroid, pancreas, ovary, andtestes, synthesize hormones brought by blood to tissuesrequiring them.


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General Functions Blood CompositionRegulation

5. Regulation of body pH- H2CO3, lactic acid, citric acid, NH3, HCO3-

tend to lower or raise blood pH. Buffer systems help maintain pHwithin limits.

6. Regulation of fluid balance between blood and tissues - Colloidalosmotic pressure of plasma > lymph causing fluid to move from

lymph to plasma, while

7. Regulation of body temperature - the high specific heat of water

allows flowing blood to transfer heat from warmer to cooler

tissues maintaining uniform temperature.


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General Functions Blood CompositionRegulation Introduction

8. Defense against infection

Large amoeboid leukocytes, polymorphonuclear leukocytes,

and monocytes engulf invading bacteria and cellular debris.

Antibody proteins include

1) agglutinins clump cells,

2) hemolysinsor cytolysinsrupture cells,

3)precipitins specifically precipitate antigenic protein,

4) antitoxinscounteract toxins of pathogenic organisms, i.e.,

diphtheria toxin.9. Prevention of hemorrhage - clotting and anti-clotting agents

circulate to safeguard against blood loss or unscheduled clots,

respectively, within the circulatory system.


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General Characteristics Blood CompositionIntroduction

Blood mass is approx. 6-7% of body weight

70 kg human has approx. 5500 ml of blood

Blood volume is more nearly proportional to surface area than

to body weight (2.0 - 2.9Kml/m2

). Measured by dye dilutiongives plasma volume

Spec. gravity is 1.055 - 1.065g/ml

Viscosity is approx. 5 - 6 times water

pH is 7.4 (7.33 to 7.51)

Unclotted blood (prevented by adding oxalate to precipitate

Ca2+). After centrifugation,yellow plasmafluid (top), white

cells (buffy coat, interface), and red cells(bottom pellet).


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General Characteristics Blood Composition

Plasma (blood without cells) can clot. Aggregation of fibrin yields

network of fibers. During centrifugation, fibrin threads pellet to

bottom leaving a clear yellow fluid called serum.

Blood clot in vivo gives serum and cells emeshed in a network offibrous strands of fibrin formed from fibrinogen (a zymogen).

Serum is a yellow fluid containing various proteins, ions, nutrients

and cellular waste products.

Blood cellsl

Erythrocytes (red cells) comprise 45% of blood volume = hematocrit

(Hct).

Leukocytes (white cells)

Platelets (thromocytes) comprise 1% of blood volume = buffy coat.


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Typical Clinical Values Blood Composition

Blood volume: 70 ml/kg

Plasma volume: 35-45 ml/kg

Red cell volume: 28-35 ml/kg Hematocrit: 41-45%


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Cellular Components Blood Composition

Formed in bone marrow

120 day average life, removed by spleen

4.4 to 6.1 x 1012cells /liter of blood

Primary function: delivery of O2to tissues and participate intransport of CO2to the lungs

Mature erythrocytes have, e.g.,

glycolytic pathway provide energy

2,3-bisphosphoglycerate plays role in O2delivery to tissues

pentose phosphate shunt yields NADPH that helps maintain the -SHgroups of SH-containing proteins in a reduced state. Example, 3-phosphoglyceraldehyde dehydrogenase, and membrane components

hemoglobinis 14-18 g/dL of blood

Erythrocytes (red blood cells, RBC)


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Blood Cellular Components

Lymphocytes, granular have multi lobed nuclei.

Monocytes are non granular have rounded nuclei.

4-12 x 109cells/liter of blood

White Cells


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Blood Components Blood CompositionBlood and Plasma proteins, amount, functions

Red cells (erythrocytes)

Hemoglobin, 11-17 percent

Plasma

Albumin, 4.7-5.7 mg % osmosis

Globulins, 1.3-2.5 mg % immunity Fibrinogen, 0.2-0.4 mg % clotting substrate

Enzymes released from cellsAlkaline Phosphatase AP, 39-117 U/liter

Lactate Dehydrogenase LDH, 100-250 U/liter

Creatine PhosphokinaseCPK,

Alanine aminotransferaseALT;

Aspartate aminotransferaseAST 7-37 U/liter

Serum glutamate oxaloacetate transaminaseSGOT

Thrombin clotting (coagulation)

Plasmin fibrinolysis

others

Oth Bl d C t C t


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Other Blood Components Components

Blood glucose, ions, lipoproteins

Glucose 70-110 mg/dL energy

Bilirubin 0.2-1.0 mg/dL (yellow)

Calcium

8.3-10.0 mg/dL various functions Uric acid 2.5-7.0 mg/dL from purines

BUN (blood urea nitrogen) 10-20 mg/dL kidney function

Cholesterol, 120-240 mg/dL cell fluidity

HDL-Cholesterol, 35-55 mg/dL removal of chol

VLDL and LDL cholesterol delivery of chol

LDL = TC - HDL - 0.2 TG about 70-100Triglycerides, 20-190 mg/dL

Many other compounds, salts, amino acids, etc.

I l bi Pl P i


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Immunoglobins Plasma Proteins

Blood proteins constitute approx. 7% solute weight

Electrophoresis resolves serum into 5-major fractions.

Albumin (54-58%)

1-globulins (6-7%) 2-globulins (8-9%) 1-globulins (13-14%)

-globulins (11-12%)Note: The different globulin fractions

contain more than one protein.

Bl d Pl P i


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Blood Plasma ProteinsDehydration

Plasma Protein concentration in human adults is from 6.0 -8.0g/dL plasma.

Dehydration gives increased levels, in other cases, highvalues are frequently due to increases in one or moreglobulin fractions.

A decrease in total plasma protein is usually associated

with a low [albumin].


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Relative Distribution of Normal Human Plasma Proteins by Electrophoresis

%

Protein Component Total Protein pI

*Albumin 55.2 4.7

*Globulins, total 44.9

A/G ratio 1.23

-Globulins 14.0 5.11-Globulins 5.32-Globulins 8.7-Globulins 13.4 5.6-Globulins 11.0 6.0

*Fibrinogen 6.5 5.4

Armstrong, SH, Jr., Budka, MJE and Morrison KC: J. Am. Chem. Soc. 69, 416 (1947)

Blood Plasma Proteins


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Albumin

4 to 5 g/dL

Synthesized in the liver

Not a glycoprotein, mol wt 68,000

One of smallest plasma proteins, ellipsoid, with net charge

of -18 at pH 7.4, pI 4.7

About 55% plasma proteins by weight, thus, its mole

fraction is much higher than the other larger proteins

Osmotic pressure of blood is approx. 75-80% due toalbumin



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Blood Plasma ProteinsAlbumin

4 to 5 g/dL

Transports diverse substances, many of which are sparingly solublein water.

free fattyacids bind tightly to albumin for transport fromliver to peripheral tissues

bilirubinis transported to liver for excretion in the bile

participation in the regulation of Ca2+, steroid hormones,and tryptophan transport

drugs, e.g., aspirin, dicumarol, penicillin G, sulfonamides,and other bind tightly to albumin.

High [albumin] observed in dehydration

Low [albumin] observed in liver disease, nephrotic syndrome,malnutrition, and protein deficiency



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, , andGlobulins

-Fetoglobulin,a major glycoprotein of human fetal plasmaand amnionic fluid, but is normally present in very lowamounts in adults. Prenatal screening.

Ceruloplasm named for its blue color due to bound Cu2+,which it transports and aids in Cu2+homeostasis. In Wilsonsdisease, bound copper is low while brain and liver levels of Cu2+increase with resulting neurological changes and liver damage

Haptoglobins form stable 1:1 complexes with hemoglobinwhen hemolysis of erythrocytes occurs intravascularly.Hence, iron in hemolytically released hemoglobin cannot beexcreted into the urine by the kidney due to the highmolecular weight of these protein complexes



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-Proteinase inhibitor(-antitrypsin)protects tissue fromdigestion by elastase. Inherited genetic defect results in 15-20%of normal serum level. Lowered levels are associated withemphysema

-Globulin includes several proteins including lipoproteins Transferrin binds Fe3+for transport to tissues especially the

reticuloendothelial system, and helps regulate [free iron] inplasma preventing iron accumulation in tissues and urinaryloss of iron. Increases in pregnant and iron-deficientindividuals

Hemopexin binds heme preventing its urinary excretion; theliver removes the complexes from the blood enablingreutilization of heme

-Globulins immunoglobulins IgA, IgD, IgE, and IgM

, ,and Globulins

Fibrinogen Fibrin Fibers Plasma Proteins


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Fibrinogen Fibrin Fibers Plasma Proteins

Blood Coagulation

A soluble, multi protein molecule made in the liver

Thrombin (from prothrombin activation)proteolysis offibrinogen releases 4 peptides.

Fibrin self-aggregates into long thread-like fibers. Cris-crossed fibrin network enmeshes cells and cell debris at atrauma site forming a soft clot.

Fibrin fibers are covalently cross-linked into hard clot.

Plasmin protease(from plasminogen activation)slowlyhydrolyzes the fibrin meshwork (clot dissolution accompanieswound healing)

The formation and dissolution of a fibrin clot is a complex,balanced set of biochemical process.

Plasma Proteins


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Plasma Proteins

END

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