blood proteins lecture 57 baynes & dominiczak, chapter 3 and 4 gene c. lavers, ph.d....

Blood ProteinsBlood ProteinsBlood ProteinsBlood ProteinsLecture 57Lecture 57Baynes & Dominiczak, Chapter 3 Baynes & Dominiczak, Chapter 3 and 4and 4

Gene C. Lavers, Ph.D.Gene C. Lavers, Ph.D.gene.lavers@ nyu.edugene.lavers@ nyu.edu

Lecture 57Lecture 57Baynes & Dominiczak, Chapter 3 Baynes & Dominiczak, Chapter 3 and 4and 4

Gene C. Lavers, Ph.D.Gene C. Lavers, Ph.D.gene.lavers@ nyu.edugene.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 otherwise copied for public or private use, without written permission from the publisher.

©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 otherwise copied for public or private use, without written permission from the publisher.

© Copyright 1999-2004 by Gene C. Lavers

2

Fluid Communication and TransportFluid Communication and Transport Blood Blood CompositionCompositionUnicellular organisms Unicellular organisms IntroductionIntroduction

Fluid Communication and TransportFluid Communication and Transport Blood Blood CompositionCompositionUnicellular organisms Unicellular organisms IntroductionIntroduction

Unicellular organismsUnicellular organisms

(( cell )) media (( cell )) media

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

mediamedia can change, e.g., depletion of food or can change, e.g., depletion of food or accumulation of waste or other substances.accumulation of waste or other substances.

intracellular fluidintracellular fluid maintenance of the proper maintenance of the proper composition if fails, then the organism ceases to composition if fails, then the organism ceases to function.function.

Unicellular organismsUnicellular organisms

(( cell )) media (( cell )) media

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

mediamedia can change, e.g., depletion of food or can change, e.g., depletion of food or accumulation of waste or other substances.accumulation of waste or other substances.

intracellular fluidintracellular fluid maintenance of the proper maintenance of the proper composition if fails, then the organism ceases to composition if fails, then the organism ceases to function.function.


3

Fluid Communication and TransportFluid Communication and Transport Blood Blood CompositionCompositionMulticellular organisms Multicellular organisms IntroductionIntroduction

Fluid Communication and TransportFluid Communication and Transport Blood Blood CompositionCompositionMulticellular organisms Multicellular organisms IntroductionIntroduction

direct exchange direct exchange direct exchangedirect exchange

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

obtain food and dispose of waste products directly by obtain food and dispose of waste products directly by diffusion with a bathing aqueous media, i.e., the diffusion with a bathing aqueous media, i.e., the interstitial fluidinterstitial fluid..

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

circulating bloodcirculating blood within capillary walls replaces essential within capillary walls replaces essential substances and removes accumulated waste thereby substances and removes accumulated waste thereby maintaining the interstitial fluid composition within maintaining the interstitial fluid composition within proper limits (by diffusion).proper limits (by diffusion).

iintracellular fluidntracellular fluid maintenance of the proper composition maintenance of the proper composition succeeds, and the tissue cells continue to function.succeeds, and the tissue cells continue to function.

direct exchange direct exchange direct exchangedirect exchange

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

obtain food and dispose of waste products directly by obtain food and dispose of waste products directly by diffusion with a bathing aqueous media, i.e., the diffusion with a bathing aqueous media, i.e., the interstitial fluidinterstitial fluid..

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

circulating bloodcirculating blood within capillary walls replaces essential within capillary walls replaces essential substances and removes accumulated waste thereby substances and removes accumulated waste thereby maintaining the interstitial fluid composition within maintaining the interstitial fluid composition within proper limits (by diffusion).proper limits (by diffusion).

iintracellular fluidntracellular fluid maintenance of the proper composition maintenance of the proper composition succeeds, and the tissue cells continue to function.succeeds, and the tissue cells continue to function.


4

Maintenance of Blood CompositionMaintenance of Blood Composition Blood Blood CompositionCompositionMechanismsMechanisms

Maintenance of Blood CompositionMaintenance of Blood Composition Blood Blood CompositionCompositionMechanismsMechanisms

Blood is maintained within physiological limits by Blood is maintained within physiological limits by special mechanismsspecial mechanisms:: Provide essential substancesProvide essential substances

Gastrointestinal system: nutrient food Gastrointestinal system: nutrient food Lungs: OLungs: O22

Remove waste productsRemove waste products Kidneys: urea, creatinine, NHKidneys: urea, creatinine, NH33, etc., etc. Lungs: COLungs: CO22 Intestines: feces (e.g.,stercobilin)Intestines: feces (e.g.,stercobilin) Skin: sweat (salts and urea)Skin: sweat (salts and urea)

Provide Provide blood cells (formed elements) from bone marrowblood cells (formed elements) from bone marrow Proteins from Liver (e.g., clotting factors)Proteins from Liver (e.g., clotting factors) Hormones from pancreas, adrenals, etc.Hormones from pancreas, adrenals, etc.

Blood is maintained within physiological limits by Blood is maintained within physiological limits by special mechanismsspecial mechanisms:: Provide essential substancesProvide essential substances

Gastrointestinal system: nutrient food Gastrointestinal system: nutrient food Lungs: OLungs: O22

Remove waste productsRemove waste products Kidneys: urea, creatinine, NHKidneys: urea, creatinine, NH33, etc., etc. Lungs: COLungs: CO22 Intestines: feces (e.g.,stercobilin)Intestines: feces (e.g.,stercobilin) Skin: sweat (salts and urea)Skin: sweat (salts and urea)

Provide Provide blood cells (formed elements) from bone marrowblood cells (formed elements) from bone marrow Proteins from Liver (e.g., clotting factors)Proteins from Liver (e.g., clotting factors) Hormones from pancreas, adrenals, etc.Hormones from pancreas, adrenals, etc.


5

General Functions General Functions Blood Blood CompositionCompositionTransportTransport

General Functions General Functions Blood Blood CompositionCompositionTransportTransport

1.1. Food transportFood transport - - absorbed digestion products from absorbed digestion products from the intestines products move to the tissues for the intestines products move to the tissues for utilization.utilization.

2.2. Waste transportWaste transport - - waste products (urea, urate, waste products (urea, urate, creatinine etc.) pass into blood then to kidneys and creatinine etc.) pass into blood then to kidneys and other organs for elimination.other organs for elimination.

3.3. Gaseous transportGaseous transport - - OO22 via oxyhemoglobin from the via oxyhemoglobin from the lungs to tissues for metabolic oxidation and energy lungs to tissues for metabolic oxidation and energy production. COproduction. CO22 from cellular oxidation is carried from from cellular oxidation is carried from tissues by blood to lungs tissues by blood to lungs for exhilation.for exhilation.

4. Hormone transport4. Hormone transport - - pituitary, thyroid, pancreas, pituitary, thyroid, pancreas, ovary, and testes, synthesize hormones brought by ovary, and testes, synthesize hormones brought by blood to tissues requiring them.blood to tissues requiring them.

1.1. Food transportFood transport - - absorbed digestion products from absorbed digestion products from the intestines products move to the tissues for the intestines products move to the tissues for utilization.utilization.

2.2. Waste transportWaste transport - - waste products (urea, urate, waste products (urea, urate, creatinine etc.) pass into blood then to kidneys and creatinine etc.) pass into blood then to kidneys and other organs for elimination.other organs for elimination.

3.3. Gaseous transportGaseous transport - - OO22 via oxyhemoglobin from the via oxyhemoglobin from the lungs to tissues for metabolic oxidation and energy lungs to tissues for metabolic oxidation and energy production. COproduction. CO22 from cellular oxidation is carried from from cellular oxidation is carried from tissues by blood to lungs tissues by blood to lungs for exhilation.for exhilation.

4. Hormone transport4. Hormone transport - - pituitary, thyroid, pancreas, pituitary, thyroid, pancreas, ovary, and testes, synthesize hormones brought by ovary, and testes, synthesize hormones brought by blood to tissues requiring them.blood to tissues requiring them.


6

General Functions General Functions Blood Blood CompositionCompositionRegulationRegulation

General Functions General Functions Blood Blood CompositionCompositionRegulationRegulation

5. 5. Regulation of body pHRegulation of body pH - - HH22COCO33, lactic acid, citric acid, NH, lactic acid, citric acid, NH33, , HCOHCO33

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

6. Regulation of fluid balance between blood and tissues - 6. Regulation of fluid balance between blood and tissues - Colloidal osmotic pressure of plasma > lymph causing fluid Colloidal osmotic pressure of plasma > lymph causing fluid to move from lymph to plasma, whileto move from lymph to plasma, while

7. Regulation of body temperature - 7. Regulation of body temperature - the high specific heat of the high specific heat of water allows flowing blood to transfer heat from warmer to water allows flowing blood to transfer heat from warmer to cooler tissues maintaining uniform temperature.cooler tissues maintaining uniform temperature.

5. 5. Regulation of body pHRegulation of body pH - - HH22COCO33, lactic acid, citric acid, NH, lactic acid, citric acid, NH33, , HCOHCO33

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

6. Regulation of fluid balance between blood and tissues - 6. Regulation of fluid balance between blood and tissues - Colloidal osmotic pressure of plasma > lymph causing fluid Colloidal osmotic pressure of plasma > lymph causing fluid to move from lymph to plasma, whileto move from lymph to plasma, while

7. Regulation of body temperature - 7. Regulation of body temperature - the high specific heat of the high specific heat of water allows flowing blood to transfer heat from warmer to water allows flowing blood to transfer heat from warmer to cooler tissues maintaining uniform temperature.cooler tissues maintaining uniform temperature.


7

General Functions General Functions Blood Blood CompositionCompositionRegulation Regulation IntroductionIntroduction

General Functions General Functions Blood Blood CompositionCompositionRegulation Regulation IntroductionIntroduction

8. Defense against infection – 8. Defense against infection – Large amoeboid leukocytes, polymorphonuclear leukocytes, Large amoeboid leukocytes, polymorphonuclear leukocytes,

and monocytes engulf invading bacteria and cellular debris. and monocytes engulf invading bacteria and cellular debris. Antibody proteins include Antibody proteins include

– 1) agglutinins clump cells,1) agglutinins clump cells,

– 2) 2) hemolysinshemolysins or or cytolysinscytolysins rupture cells, rupture cells,

– 3) 3) precipitins precipitins specifically precipitate antigenic protein, specifically precipitate antigenic protein,

– 4) 4) antitoxinsantitoxins counteract toxins of pathogenic organisms, i.e., counteract toxins of pathogenic organisms, i.e., diphtheria toxin. diphtheria toxin.

9. Prevention of hemorrhage - 9. Prevention of hemorrhage - clotting and anti-clotting agents clotting and anti-clotting agents circulate to safeguard against blood loss or unscheduled circulate to safeguard against blood loss or unscheduled clots, respectively, within the circulatory system.clots, respectively, within the circulatory system.

8. Defense against infection – 8. Defense against infection – Large amoeboid leukocytes, polymorphonuclear leukocytes, Large amoeboid leukocytes, polymorphonuclear leukocytes,

and monocytes engulf invading bacteria and cellular debris. and monocytes engulf invading bacteria and cellular debris. Antibody proteins include Antibody proteins include

– 1) agglutinins clump cells,1) agglutinins clump cells,

– 2) 2) hemolysinshemolysins or or cytolysinscytolysins rupture cells, rupture cells,

– 3) 3) precipitins precipitins specifically precipitate antigenic protein, specifically precipitate antigenic protein,

– 4) 4) antitoxinsantitoxins counteract toxins of pathogenic organisms, i.e., counteract toxins of pathogenic organisms, i.e., diphtheria toxin. diphtheria toxin.

9. Prevention of hemorrhage - 9. Prevention of hemorrhage - clotting and anti-clotting agents clotting and anti-clotting agents circulate to safeguard against blood loss or unscheduled circulate to safeguard against blood loss or unscheduled clots, respectively, within the circulatory system.clots, respectively, within the circulatory system.


8

General Characteristics General Characteristics Blood Blood CompositionComposition IntroductionIntroduction

General Characteristics General Characteristics Blood Blood CompositionComposition IntroductionIntroduction

Blood massBlood mass is approx. 6-7% of body weightis approx. 6-7% of body weight 70 kg human 70 kg human has approx. 5500 ml of bloodhas approx. 5500 ml of blood Blood volumeBlood volume is more nearly proportional to surface area is more nearly proportional to surface area

than to body weight (2.0 - 2.9Kml/mthan to body weight (2.0 - 2.9Kml/m22). Measured by dye ). Measured by dye dilution gives plasma volumedilution gives plasma volume

Spec. gravitySpec. gravity is 1.055 - 1.065is 1.055 - 1.065 g/mlg/ml ViscosityViscosity is approx. 5 - 6 times wateris approx. 5 - 6 times water pHpH is 7.4 is 7.4 (7.33 to 7.51)(7.33 to 7.51) Unclotted bloodUnclotted blood (prevented by adding oxalate to precipitate (prevented by adding oxalate to precipitate

CaCa2+2+)). After centrifugation, . After centrifugation, yellow plasmayellow plasma fluid (top), white fluid (top), white cells (buffy coat, interface), and cells (buffy coat, interface), and red cellsred cells (bottom pellet). (bottom pellet).

Blood massBlood mass is approx. 6-7% of body weightis approx. 6-7% of body weight 70 kg human 70 kg human has approx. 5500 ml of bloodhas approx. 5500 ml of blood Blood volumeBlood volume is more nearly proportional to surface area is more nearly proportional to surface area

than to body weight (2.0 - 2.9Kml/mthan to body weight (2.0 - 2.9Kml/m22). Measured by dye ). Measured by dye dilution gives plasma volumedilution gives plasma volume

Spec. gravitySpec. gravity is 1.055 - 1.065is 1.055 - 1.065 g/mlg/ml ViscosityViscosity is approx. 5 - 6 times wateris approx. 5 - 6 times water pHpH is 7.4 is 7.4 (7.33 to 7.51)(7.33 to 7.51) Unclotted bloodUnclotted blood (prevented by adding oxalate to precipitate (prevented by adding oxalate to precipitate

CaCa2+2+)). After centrifugation, . After centrifugation, yellow plasmayellow plasma fluid (top), white fluid (top), white cells (buffy coat, interface), and cells (buffy coat, interface), and red cellsred cells (bottom pellet). (bottom pellet).


9

General Characteristics General Characteristics Blood Blood CompositionCompositionGeneral Characteristics General Characteristics Blood Blood CompositionComposition

PlasmaPlasma (blood without cells) can clot. Aggregation of fibrin (blood without cells) can clot. Aggregation of fibrin

yields network of fibers. During centrifugation, fibrin threads yields network of fibers. During centrifugation, fibrin threads

pellet to bottom leaving a clear yellow fluid called serum.pellet to bottom leaving a clear yellow fluid called serum.

Blood clotBlood clot in vivo in vivo gives serum and cells emeshed in a network of gives serum and cells emeshed in a network of

fibrous strands of fibrin formed from fibrinogen (a zymogen).fibrous strands of fibrin formed from fibrinogen (a zymogen).

SerumSerum is a yellow fluid containing various proteins, ions, is a yellow fluid containing various proteins, ions,

nutrients and cellular waste products. nutrients and cellular waste products.

Blood cellslBlood cellsl

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

(Hct).(Hct).

LeukocytesLeukocytes (white cells) (white cells)

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

PlasmaPlasma (blood without cells) can clot. Aggregation of fibrin (blood without cells) can clot. Aggregation of fibrin

yields network of fibers. During centrifugation, fibrin threads yields network of fibers. During centrifugation, fibrin threads

pellet to bottom leaving a clear yellow fluid called serum.pellet to bottom leaving a clear yellow fluid called serum.

Blood clotBlood clot in vivo in vivo gives serum and cells emeshed in a network of gives serum and cells emeshed in a network of

fibrous strands of fibrin formed from fibrinogen (a zymogen).fibrous strands of fibrin formed from fibrinogen (a zymogen).

SerumSerum is a yellow fluid containing various proteins, ions, is a yellow fluid containing various proteins, ions,

nutrients and cellular waste products. nutrients and cellular waste products.

Blood cellslBlood cellsl

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

(Hct).(Hct).

LeukocytesLeukocytes (white cells) (white cells)

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


10

Typical Clinical Values Typical Clinical Values Blood Blood CompositionCompositionTypical Clinical Values Typical Clinical Values Blood Blood CompositionComposition

Blood volume: Blood volume: 70 ml/kg70 ml/kg

Plasma volume: Plasma volume: 35-45 ml/kg35-45 ml/kg

Red cell volume: Red cell volume: 28-35 ml/kg28-35 ml/kg

Hematocrit: 41-45%Hematocrit: 41-45%

Blood volume: Blood volume: 70 ml/kg70 ml/kg

Plasma volume: Plasma volume: 35-45 ml/kg35-45 ml/kg

Red cell volume: Red cell volume: 28-35 ml/kg28-35 ml/kg

Hematocrit: 41-45%Hematocrit: 41-45%


11

Cellular ComponentsCellular Components Blood Blood CompositionComposition Cellular ComponentsCellular Components Blood Blood CompositionComposition

Formed in bone marrowFormed in bone marrow 120 day average life, 120 day average life, removed by spleenremoved by spleen 4.4 to 6.1 x 104.4 to 6.1 x 101212 cells /liter of blood cells /liter of blood Primary function: delivery of OPrimary function: delivery of O22 to tissues and to tissues and

participate in transport of COparticipate in transport of CO22 to the lungs to the lungs Mature erythrocytes have, e.g.,Mature erythrocytes have, e.g.,

glycolytic pathway glycolytic pathway provide energyprovide energy 2,3-bisphosphoglycerate plays 2,3-bisphosphoglycerate plays role in Orole in O22 delivery to tissues delivery to tissues pentose phosphate shunt pentose phosphate shunt yields NADPH that helps maintain yields NADPH that helps maintain

the -SH groups of SH-containing proteins in a reduced state. the -SH groups of SH-containing proteins in a reduced state. Example, Example, 3-phosphoglyceraldehyde dehydrogenase3-phosphoglyceraldehyde dehydrogenase, and , and membrane componentsmembrane components

hemoglobinhemoglobin is 14-18 g/dL of bloodis 14-18 g/dL of blood

Formed in bone marrowFormed in bone marrow 120 day average life, 120 day average life, removed by spleenremoved by spleen 4.4 to 6.1 x 104.4 to 6.1 x 101212 cells /liter of blood cells /liter of blood Primary function: delivery of OPrimary function: delivery of O22 to tissues and to tissues and

participate in transport of COparticipate in transport of CO22 to the lungs to the lungs Mature erythrocytes have, e.g.,Mature erythrocytes have, e.g.,

glycolytic pathway glycolytic pathway provide energyprovide energy 2,3-bisphosphoglycerate plays 2,3-bisphosphoglycerate plays role in Orole in O22 delivery to tissues delivery to tissues pentose phosphate shunt pentose phosphate shunt yields NADPH that helps maintain yields NADPH that helps maintain

the -SH groups of SH-containing proteins in a reduced state. the -SH groups of SH-containing proteins in a reduced state. Example, Example, 3-phosphoglyceraldehyde dehydrogenase3-phosphoglyceraldehyde dehydrogenase, and , and membrane componentsmembrane components

hemoglobinhemoglobin is 14-18 g/dL of bloodis 14-18 g/dL of blood

Erythrocytes (red blood cells, Erythrocytes (red blood cells,

RBC)RBC) Erythrocytes (red blood cells, Erythrocytes (red blood cells,

RBC)RBC)


12

BloodBlood Cellular Cellular ComponentsComponents

BloodBlood Cellular Cellular ComponentsComponents

Lymphocytes, granular – have multi lobed nuclei.Lymphocytes, granular – have multi lobed nuclei.

Monocytes are non granular – have rounded nuclei.Monocytes are non granular – have rounded nuclei.

4-12 x 104-12 x 1099 cells/liter of blood cells/liter of blood

Lymphocytes, granular – have multi lobed nuclei.Lymphocytes, granular – have multi lobed nuclei.

Monocytes are non granular – have rounded nuclei.Monocytes are non granular – have rounded nuclei.

4-12 x 104-12 x 1099 cells/liter of blood cells/liter of blood

White CellsWhite Cells


13

Blood Blood Components Components Blood Blood CompositionCompositionBlood and Plasma proteins, amount, functionsBlood and Plasma proteins, amount, functions

Blood Blood Components Components Blood Blood CompositionCompositionBlood and Plasma proteins, amount, functionsBlood and Plasma proteins, amount, functions

Red cells (erythrocytes)Red cells (erythrocytes)– Hemoglobin, 11-17 percentHemoglobin, 11-17 percent

PlasmaPlasma– Albumin, Albumin, 4.7-5.7 mg 4.7-5.7 mg % osmosis% osmosis– Globulins, Globulins, 1.3-2.5 mg %1.3-2.5 mg % immunity immunity– Fibrinogen, Fibrinogen, 0.2-0.4 mg %0.2-0.4 mg % clotting substrate clotting substrate– Enzymes Enzymes released from cellsreleased from cells

Alkaline Phosphatase APAlkaline Phosphatase AP, , 39-117 U/liter39-117 U/liter Lactate Dehydrogenase LDHLactate Dehydrogenase LDH,, 100-250 U/liter100-250 U/liter Creatine PhosphokinaseCreatine Phosphokinase CPKCPK, , Alanine aminotransferaseAlanine aminotransferase ALTALT ; ; Aspartate aminotransferaseAspartate aminotransferase ASTAST 7-37 U/liter7-37 U/liter Serum glutamate oxaloacetate transaminaseSerum glutamate oxaloacetate transaminase SGOT SGOT ThrombinThrombin clotting (coagulation)clotting (coagulation) Plasmin Plasmin fibrinolysisfibrinolysis othersothers

Red cells (erythrocytes)Red cells (erythrocytes)– Hemoglobin, 11-17 percentHemoglobin, 11-17 percent

PlasmaPlasma– Albumin, Albumin, 4.7-5.7 mg 4.7-5.7 mg % osmosis% osmosis– Globulins, Globulins, 1.3-2.5 mg %1.3-2.5 mg % immunity immunity– Fibrinogen, Fibrinogen, 0.2-0.4 mg %0.2-0.4 mg % clotting substrate clotting substrate– Enzymes Enzymes released from cellsreleased from cells

Alkaline Phosphatase APAlkaline Phosphatase AP, , 39-117 U/liter39-117 U/liter Lactate Dehydrogenase LDHLactate Dehydrogenase LDH,, 100-250 U/liter100-250 U/liter Creatine PhosphokinaseCreatine Phosphokinase CPKCPK, , Alanine aminotransferaseAlanine aminotransferase ALTALT ; ; Aspartate aminotransferaseAspartate aminotransferase ASTAST 7-37 U/liter7-37 U/liter Serum glutamate oxaloacetate transaminaseSerum glutamate oxaloacetate transaminase SGOT SGOT ThrombinThrombin clotting (coagulation)clotting (coagulation) Plasmin Plasmin fibrinolysisfibrinolysis othersothers


14

Other Blood Components Other Blood Components ComponentsComponentsOther Blood Components Other Blood Components ComponentsComponents

Blood glucose, ions, lipoproteinsBlood glucose, ions, lipoproteins– Glucose – Glucose – 70-110 mg/dL70-110 mg/dL energy energy– Bilirubin – Bilirubin – 0.2-1.0 mg/dL0.2-1.0 mg/dL (yellow) (yellow)– Calcium – Calcium – 8.3-10.0 mg/dL8.3-10.0 mg/dL various various

functionsfunctions– Uric acid – Uric acid – 2.5-7.0 mg/dL2.5-7.0 mg/dL from purines from purines– BUN (BUN (bblood lood uurea rea nnitrogen) – itrogen) – 10-20 mg/dL10-20 mg/dL kidney function kidney function– Cholesterol, Cholesterol, 120-240 mg/dL120-240 mg/dL cell fluidity cell fluidity– HDL-Cholesterol, HDL-Cholesterol, 35-55 mg/dL35-55 mg/dL removal of chol removal of chol– VLDL and LDL cholesterol VLDL and LDL cholesterol delivery of choldelivery of chol– LDL = TC - HDL - 0.2 TG LDL = TC - HDL - 0.2 TG about 70-100 about 70-100

Triglycerides, Triglycerides, 20-190 mg/dL20-190 mg/dL – Many other compounds, salts, amino acids, etc.Many other compounds, salts, amino acids, etc.

Blood glucose, ions, lipoproteinsBlood glucose, ions, lipoproteins– Glucose – Glucose – 70-110 mg/dL70-110 mg/dL energy energy– Bilirubin – Bilirubin – 0.2-1.0 mg/dL0.2-1.0 mg/dL (yellow) (yellow)– Calcium – Calcium – 8.3-10.0 mg/dL8.3-10.0 mg/dL various various

functionsfunctions– Uric acid – Uric acid – 2.5-7.0 mg/dL2.5-7.0 mg/dL from purines from purines– BUN (BUN (bblood lood uurea rea nnitrogen) – itrogen) – 10-20 mg/dL10-20 mg/dL kidney function kidney function– Cholesterol, Cholesterol, 120-240 mg/dL120-240 mg/dL cell fluidity cell fluidity– HDL-Cholesterol, HDL-Cholesterol, 35-55 mg/dL35-55 mg/dL removal of chol removal of chol– VLDL and LDL cholesterol VLDL and LDL cholesterol delivery of choldelivery of chol– LDL = TC - HDL - 0.2 TG LDL = TC - HDL - 0.2 TG about 70-100 about 70-100

Triglycerides, Triglycerides, 20-190 mg/dL20-190 mg/dL – Many other compounds, salts, amino acids, etc.Many other compounds, salts, amino acids, etc.


15

Immunoglobins Immunoglobins Plasma Plasma ProteinsProteins

Immunoglobins Immunoglobins Plasma Plasma ProteinsProteins

Blood proteins constitute approx. 7% solute weightBlood proteins constitute approx. 7% solute weightElectrophoresis resolves serum into 5-major Electrophoresis resolves serum into 5-major

fractions.fractions.

Albumin Albumin (54-58%)(54-58%) 11-globulins -globulins (6-7%)(6-7%) 22-globulins -globulins (8-9%)(8-9%) 11-globulins -globulins (13-14%)(13-14%) -globulins -globulins (11-12%)(11-12%) Note: The different globulin fractionsNote: The different globulin fractions contain more than one protein.contain more than one protein.

Blood proteins constitute approx. 7% solute weightBlood proteins constitute approx. 7% solute weightElectrophoresis resolves serum into 5-major Electrophoresis resolves serum into 5-major

fractions.fractions.

Albumin Albumin (54-58%)(54-58%) 11-globulins -globulins (6-7%)(6-7%) 22-globulins -globulins (8-9%)(8-9%) 11-globulins -globulins (13-14%)(13-14%) -globulins -globulins (11-12%)(11-12%) Note: The different globulin fractionsNote: The different globulin fractions contain more than one protein.contain more than one protein.


16

BloodBlood Plasma Plasma ProteinsProteinsDehydration Dehydration

BloodBlood Plasma Plasma ProteinsProteinsDehydration Dehydration

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

Dehydration gives increased levels, in other Dehydration gives increased levels, in other cases, high values are frequently due to increases cases, high values are frequently due to increases in one or more globulin fractions.in one or more globulin fractions.

A decrease in total plasma protein is usually A decrease in total plasma protein is usually

associated with a low [albumin].associated with a low [albumin].

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

Dehydration gives increased levels, in other Dehydration gives increased levels, in other cases, high values are frequently due to increases cases, high values are frequently due to increases in one or more globulin fractions.in one or more globulin fractions.

A decrease in total plasma protein is usually A decrease in total plasma protein is usually

associated with a low [albumin].associated with a low [albumin].


17

Relative Distribution of Normal Human Plasma Proteins by Relative Distribution of Normal Human Plasma Proteins by ElectrophoresisElectrophoresisRelative Distribution of Normal Human Plasma Proteins by Relative Distribution of Normal Human Plasma Proteins by ElectrophoresisElectrophoresis

% %

Protein ComponentProtein Component Total ProteinTotal Protein pIpI

*Albumin*Albumin 55.255.2 4.7 4.7

*Globulins, total*Globulins, total 44.944.9

A/G ratioA/G ratio 1.23 1.23

--GlobulinsGlobulins 14.014.0 5.1 5.1

11--GlobulinsGlobulins 5.3 5.3




*Fibrinogen*Fibrinogen 6.5 6.5 5.4 5.4

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

% %

Protein ComponentProtein Component Total ProteinTotal Protein pIpI

*Albumin*Albumin 55.255.2 4.7 4.7

*Globulins, total*Globulins, total 44.944.9

A/G ratioA/G ratio 1.23 1.23






*Fibrinogen*Fibrinogen 6.5 6.5 5.4 5.4

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


18

BloodBlood Plasma Plasma

ProteinsProteins

AlbuminAlbumin

BloodBlood Plasma Plasma

ProteinsProteins

AlbuminAlbumin

4 to 5 g/dL4 to 5 g/dL Synthesized in the liverSynthesized in the liver Not a glycoprotein, Not a glycoprotein, mol wt 68,000mol wt 68,000 One of smallest plasma proteins, One of smallest plasma proteins, ellipsoid, with net ellipsoid, with net

charge of -18 at pH 7.4, pI 4.7charge of -18 at pH 7.4, pI 4.7 About 55% plasma proteins by weight, thus, its mole About 55% plasma proteins by weight, thus, its mole

fraction is much higher than the other larger proteinsfraction is much higher than the other larger proteins Osmotic pressure of blood is approx. 75-80% due to Osmotic pressure of blood is approx. 75-80% due to

albuminalbumin

4 to 5 g/dL4 to 5 g/dL Synthesized in the liverSynthesized in the liver Not a glycoprotein, Not a glycoprotein, mol wt 68,000mol wt 68,000 One of smallest plasma proteins, One of smallest plasma proteins, ellipsoid, with net ellipsoid, with net

charge of -18 at pH 7.4, pI 4.7charge of -18 at pH 7.4, pI 4.7 About 55% plasma proteins by weight, thus, its mole About 55% plasma proteins by weight, thus, its mole

fraction is much higher than the other larger proteinsfraction is much higher than the other larger proteins Osmotic pressure of blood is approx. 75-80% due to Osmotic pressure of blood is approx. 75-80% due to

albuminalbumin


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BloodBlood Plasma Plasma ProteinsProteinsAlbuminAlbumin

BloodBlood Plasma Plasma ProteinsProteinsAlbuminAlbumin

4 to 5 g/dL4 to 5 g/dL Transports diverse substances, Transports diverse substances, many of which are sparingly many of which are sparingly

soluble in water.soluble in water.– free fattyfree fatty acids bind tightly to albumin for transport acids bind tightly to albumin for transport

from liver to peripheral tissuesfrom liver to peripheral tissues– bilirubinbilirubin is transported to liver for excretion in the bile is transported to liver for excretion in the bile– participation in the regulation of Caparticipation in the regulation of Ca2+2+, steroid , steroid

hormones, and tryptophan transporthormones, and tryptophan transport– drugsdrugs, e.g., aspirin, dicumarol, penicillin G, , e.g., aspirin, dicumarol, penicillin G,

sulfonamides, and other bind tightly to albumin.sulfonamides, and other bind tightly to albumin. High [albumin] observed in dehydrationHigh [albumin] observed in dehydration Low [albumin] observed in liver disease, nephrotic Low [albumin] observed in liver disease, nephrotic

syndrome, malnutrition, and protein deficiencysyndrome, malnutrition, and protein deficiency

4 to 5 g/dL4 to 5 g/dL Transports diverse substances, Transports diverse substances, many of which are sparingly many of which are sparingly

soluble in water.soluble in water.– free fattyfree fatty acids bind tightly to albumin for transport acids bind tightly to albumin for transport

from liver to peripheral tissuesfrom liver to peripheral tissues– bilirubinbilirubin is transported to liver for excretion in the bile is transported to liver for excretion in the bile– participation in the regulation of Caparticipation in the regulation of Ca2+2+, steroid , steroid

hormones, and tryptophan transporthormones, and tryptophan transport– drugsdrugs, e.g., aspirin, dicumarol, penicillin G, , e.g., aspirin, dicumarol, penicillin G,

sulfonamides, and other bind tightly to albumin.sulfonamides, and other bind tightly to albumin. High [albumin] observed in dehydrationHigh [albumin] observed in dehydration Low [albumin] observed in liver disease, nephrotic Low [albumin] observed in liver disease, nephrotic

syndrome, malnutrition, and protein deficiencysyndrome, malnutrition, and protein deficiency


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Blood Blood Plasma Plasma ProteinsProteins , , , , andand GlobulinsGlobulins

Blood Blood Plasma Plasma ProteinsProteins , , , , andand GlobulinsGlobulins

--FetoglobulinFetoglobulin,, a major glycoprotein of human fetal a major glycoprotein of human fetal plasma and amnionic fluid, but is normally present in plasma and amnionic fluid, but is normally present in very low amounts in adults. Prenatal screening.very low amounts in adults. Prenatal screening.

CeruloplasmCeruloplasm named for its blue color due to bound Cunamed for its blue color due to bound Cu2+2+, , which it transports and aids in Cuwhich it transports and aids in Cu2+2+ homeostasis. homeostasis. In In Wilson’s diseaseWilson’s disease, bound copper is low while brain and liver , bound copper is low while brain and liver levels of levels of CuCu2+2+ increase with resulting neurological changes and increase with resulting neurological changes and liver damageliver damage

HaptoglobinsHaptoglobins form stable 1:1 complexes with form stable 1:1 complexes with hemoglobin when hemolysis of erythrocytes occurs hemoglobin when hemolysis of erythrocytes occurs intravascularly. Hence, iron in hemolytically released intravascularly. Hence, iron in hemolytically released hemoglobin cannot be excreted into the urine by the hemoglobin cannot be excreted into the urine by the kidney due to the high molecular weight of these protein kidney due to the high molecular weight of these protein complexescomplexes

--FetoglobulinFetoglobulin,, a major glycoprotein of human fetal a major glycoprotein of human fetal plasma and amnionic fluid, but is normally present in plasma and amnionic fluid, but is normally present in very low amounts in adults. Prenatal screening.very low amounts in adults. Prenatal screening.

CeruloplasmCeruloplasm named for its blue color due to bound Cunamed for its blue color due to bound Cu2+2+, , which it transports and aids in Cuwhich it transports and aids in Cu2+2+ homeostasis. homeostasis. In In Wilson’s diseaseWilson’s disease, bound copper is low while brain and liver , bound copper is low while brain and liver levels of levels of CuCu2+2+ increase with resulting neurological changes and increase with resulting neurological changes and liver damageliver damage

HaptoglobinsHaptoglobins form stable 1:1 complexes with form stable 1:1 complexes with hemoglobin when hemolysis of erythrocytes occurs hemoglobin when hemolysis of erythrocytes occurs intravascularly. Hence, iron in hemolytically released intravascularly. Hence, iron in hemolytically released hemoglobin cannot be excreted into the urine by the hemoglobin cannot be excreted into the urine by the kidney due to the high molecular weight of these protein kidney due to the high molecular weight of these protein complexescomplexes


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BloodBlood Plasma Plasma ProteinsProteins

BloodBlood Plasma Plasma ProteinsProteins

-Proteinase inhibitor-Proteinase inhibitor ((-antitrypsin)-antitrypsin) protects tissue protects tissue from digestion by from digestion by elastaseelastase. Inherited genetic defect . Inherited genetic defect results in 15-20% of normal serum level. Lowered levels results in 15-20% of normal serum level. Lowered levels are associated with emphysemaare associated with emphysema

-Globulin-Globulin includes several proteins including includes several proteins including lipoproteinslipoproteins TransferrinTransferrin binds Febinds Fe3+3+ for transport to tissues for transport to tissues

especially the reticuloendothelial system, and helps especially the reticuloendothelial system, and helps regulate [free iron] in plasma preventing iron regulate [free iron] in plasma preventing iron accumulation in tissues and urinary loss of iron. accumulation in tissues and urinary loss of iron. Increases in pregnant and iron-deficient individualsIncreases in pregnant and iron-deficient individuals

HemopexinHemopexin binds heme preventing its urinary binds heme preventing its urinary excretion; the liver removes the complexes from the excretion; the liver removes the complexes from the blood enabling reutilization of hemeblood enabling reutilization of heme

-Globulins-Globulins immunoglobulins IgA, IgD, IgE, and IgMimmunoglobulins IgA, IgD, IgE, and IgM

-Proteinase inhibitor-Proteinase inhibitor ((-antitrypsin)-antitrypsin) protects tissue protects tissue from digestion by from digestion by elastaseelastase. Inherited genetic defect . Inherited genetic defect results in 15-20% of normal serum level. Lowered levels results in 15-20% of normal serum level. Lowered levels are associated with emphysemaare associated with emphysema

-Globulin-Globulin includes several proteins including includes several proteins including lipoproteinslipoproteins TransferrinTransferrin binds Febinds Fe3+3+ for transport to tissues for transport to tissues

especially the reticuloendothelial system, and helps especially the reticuloendothelial system, and helps regulate [free iron] in plasma preventing iron regulate [free iron] in plasma preventing iron accumulation in tissues and urinary loss of iron. accumulation in tissues and urinary loss of iron. Increases in pregnant and iron-deficient individualsIncreases in pregnant and iron-deficient individuals

HemopexinHemopexin binds heme preventing its urinary binds heme preventing its urinary excretion; the liver removes the complexes from the excretion; the liver removes the complexes from the blood enabling reutilization of hemeblood enabling reutilization of heme

-Globulins-Globulins immunoglobulins IgA, IgD, IgE, and IgMimmunoglobulins IgA, IgD, IgE, and IgM

, , , , andand GlobulinsGlobulins, , , , andand GlobulinsGlobulins


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Fibrinogen Fibrinogen Fibrin Fibrin Fibers Fibers Plasma Plasma ProteinsProteinsBlood CoagulationBlood Coagulation

Fibrinogen Fibrinogen Fibrin Fibrin Fibers Fibers Plasma Plasma ProteinsProteinsBlood CoagulationBlood Coagulation

A soluble, multi protein molecule made in the liverA soluble, multi protein molecule made in the liver Thrombin Thrombin (from prothrombin activation)(from prothrombin activation) proteolysis of proteolysis of

fibrinogen releases 4 peptides. fibrinogen releases 4 peptides. Fibrin self-aggregates Fibrin self-aggregates into long thread-like fibers. into long thread-like fibers.

Cris-crossed fibrin network enmeshes cells and cell Cris-crossed fibrin network enmeshes cells and cell debris at a trauma site forming a debris at a trauma site forming a soft clotsoft clot..

Fibrin fibers are covalently cross-linked Fibrin fibers are covalently cross-linked into into hard hard clot.clot.

Plasmin proteasePlasmin protease(from plasminogen activation)(from plasminogen activation) slowly slowly hydrolyzes the fibrin meshwork hydrolyzes the fibrin meshwork (clot dissolution (clot dissolution accompanies wound healing)accompanies wound healing)

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

A soluble, multi protein molecule made in the liverA soluble, multi protein molecule made in the liver Thrombin Thrombin (from prothrombin activation)(from prothrombin activation) proteolysis of proteolysis of

fibrinogen releases 4 peptides. fibrinogen releases 4 peptides. Fibrin self-aggregates Fibrin self-aggregates into long thread-like fibers. into long thread-like fibers.

Cris-crossed fibrin network enmeshes cells and cell Cris-crossed fibrin network enmeshes cells and cell debris at a trauma site forming a debris at a trauma site forming a soft clotsoft clot..

Fibrin fibers are covalently cross-linked Fibrin fibers are covalently cross-linked into into hard hard clot.clot.

Plasmin proteasePlasmin protease(from plasminogen activation)(from plasminogen activation) slowly slowly hydrolyzes the fibrin meshwork hydrolyzes the fibrin meshwork (clot dissolution (clot dissolution accompanies wound healing)accompanies wound healing)

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


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Plasma Plasma ProteinsProteins

Plasma Plasma ProteinsProteins

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blood proteins lecture 57 baynes & dominiczak, chapter 3 and 4 gene c. lavers, ph.d....

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