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Journal of Parenteral and Enteral

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 DOI: 10.1177/0148607191015002207

1991 15: 207JPEN J Parenter Enteral NutrJohn P. Doweiko and Dominic J. Nompleggi

Reviews: Role of Albumin in Human Physiology and Pathophysiology  

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Reviews

Role of Albumin in Human Physiology and Pathophysiology

JOHN P. DOWEIKO, M.D. AND DOMINIC J. NOMPLEGGI, M.D., PH.D.

From the Department of Medicine and Nutritional Support Services, New England Deaconess Hospital, and the Hematology andGastroenterology Divisions, Brigham and Women’s Hospital, Boston Massachusetts

Reprint requests: John P. Doweiko, MD, Division of Hematology,Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02215.

ABSTRACT. Albumin is one of the major products of hepaticprotein synthesis. Although it is a small molecule, it is an

important diagnostic and prognostic determinant, as well as auseful therapeutic agent. A review of the evolution and struc-ture of albumin as well as a description of its colloidal andbuffering properties is presented. Synthesis, distribution, and

catabolism, the major determinants of serum albumin level, arediscussed. Emphasis is given to those mechanisms responsiblefor the regulation of these processes, including the importanceof nutritional status on substrate availability, energy supply,and hormonal modulation. (Journal of Parenteral and EnteralNutrition 15:207-211, 1991)

Albumin, the predominant product of hepatic proteinsynthesis, has assumed dual importance both as a diag-nostic and prognostic determinant in various diseasestates and as a useful therapeutic agent. It is one of themost ubiquitous constituents of the human body and hasmultiple roles in its physiology. Despite its relative abun-dance, albumin has been among the more engimaticproteins. The importance of this protein was first rec-ognized by Ancell in 1837.~ Since then, its complexitieshave only begun to unfold.

EVOLUTION AND STRUCTURE OF ALBUMIN

a-Fetoprotein is the fetal counterpart of adult albumin;the two share similar properties. The genes for the twoare on the same chromosome in mice; in humans it isknown that the albumin gene is on chromosome numberfour.’ Albumin, a-fetoprotein, and myoglobin probablyevolved from the same ancestral gene about 300-500million years ago.3°4 Over millennia, this primordium wastriplicated via a process of tandem amplification, a ran-dom process occurring during mitosis, which after gen-erating two adjacent sequences, enhances probability ofa similar replication process.3 The multiple disulfidebridges which help to stabilize the albumin moleculedeveloped at a later time, and myoglobin, its descendanthemoglobin, and a-fetoprotein all diverged later fromthis ancestral gene.

Albumin, compared to other plasma proteins, is a

relatively small molecule, consisting of a single polypep-tide chain of 584 amino acids.5 It has a total molecularweight of 69,000 Dalton, arranged predominantly into ahelices held together by 17 disulfide bridgeS.3 The archi-tectural unit of the molecule is the subdomain.5 Eachsubdomain corresponds to the product of the primordialgene and consists of three contiguous a helices arrangedin parallel.5 A pair of subdomains face each other in an

antiparallel fashion to form a domain. Thus, each domainis a cylindrical structure composed of six parallel poly-peptide chains.’ The outside of the cylinder is mainlypolar and the central channel of the domain is lined

by hydrophobic residues producing a sanctuary and po-tential binding site for other hydrophobic species.’Three domains together compose the albumin molecule(Fig. 1).A large number of proline molecules in the segments

between subdomains allows one to move in relation toanother.’ So binding of molecules by albumin maychange the spatial orientation of subdomains to promoteor inhibit other potential binding sites on albumin forother molecules.’ Thus, the molecule has a highly orga-nized, mainly hydrophobic internal structure’ stabilizedby disulfide bonds between half cystine residues and amore flexible surface that is mainly hydrophilic.’ Theellipsoidal shape of the molecule gives a solution ofalbumin the property of very low viscosity.&dquo;’

COLLOIDAL AND BUFFERING PROPERTIES

OF ALBUMIN

During health, the human body contains a total ofabout 200 g of albumin. The normal serum albumin levelis 3.5 to 5.0 g/dL’ accounting for about 50% of the serumproteins. An important function of albumin in normalphysiology is its role in fluid distribution throughout thebody because of its colloidal properties. Colloid oncoticpressure is a function of the number of particles withina compartment and is independent of their composition.Within the intravascular space, albumin provides up to75% of the normal oncotic pressure, 4,6,9,10,12 especiallybelow 3 g/dL, with little relative increase in this functionabove this level.&dquo; Albumin provides a greater oncoticeffect than anticipated because of Gibbs-Donnan equilib-rium : A difference in the concentration of large, chargedmolecules such as albumin on either side of a semiperme-able membrane prevents migration of small diffusableions. Tissue oncotic pressure varies among organs and isa proportion of that of plasma. 11 Because of its charge,

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6-

FIG. 1. A conceptual model of the albumin molecule. Each subdomainconsists of three contiguous polypeptide chains arranged in parallel, asindicated by the arrows. Two subdomains face each other in an anti-parallel fashion to form a domain. Three domains together form thecomplete molecule.

water solubility and the large extravascular pool, albuminhas a major role in the regulation of the fluid concentra-tion of different tissues.11,12 Although some tissues suchas skin contain relatively large amounts of albumin,much of this is bound to the tissue and is unavailable toexert its full oncotic effect. 13Because of its unique composition and abundance,

albumin plays an important role in acid-base physiology.The molecule contains a number of histidine residues,each with a pKa close to 7.4, making the protein able tofunction as a blood buffer.&dquo; However, it is relatively lessimportant in this capacity than hemoglobin.14 Approxi-mately two thirds of the normal anion gap originatesfrom plasma proteins,15 and albumin with its net chargeof negative 19 at normal serum pH is responsible foralmost half of the normal anion gap. Therefore, changesin the level of serum albumin may contribute to changesin serum acid-base status. Any increase in serum albuminlevel increases the anion gap.15 Related to this, alkalemiamay cause release of hydrogen ions from albumin andother plasma proteins, thus increasing their net ioniccharge and therefore the anion gap: A chloride-respon-sive metabolic alkalosis results.15 A decrease in serumalbumin may reduce the anion gap, contributing towarda metabolic alkalosis: &dquo;primary hypoproteinemic alka-losis.&dquo;16 One study has shown that a decrease of albuminof 1 g/dL decreases the normal anion gap by 3 mEq/literand causes an increase in serum bicarbonate by 3.5 mM/dL.16 Another study has shown that although hypoalbu-minemia tends to cause a low anion gap, there is no wayof predicting the individual anion gap from albuminlevels alone.17

PHENOTYPIC VARIANTS OF ALBUMIN

Albumin may exist in man as genetic or less frequentlyposttranscriptional variants, which for the most part are

antigenically identical to the prevalent molecule butdiffer in electrophoretic pattern.1,4,18 The genotype con-tains two autosomal codominant alleles for albumin, theexpression of which determines the albumin phenotype.Over 80 albumin variants have been identified.2° Most ofthese variants exist in the heterozygous state; homozy-gous allotypes are very rare.19 Although some variantalbumins may be harmful, most heterozygotes are

healthy. However, the variants may have subtle altera-tions in properties.’

Pedigree analysis of genetic variants has confirmedthat the genes for albumin are inherited by Mendeliancodominant autosomal alleles.4,7 Different albumin typesare found to reflect population differences, with thehighest frequency occurring in American Indians and thelowest within Eurasian peoples.2oThere is a condition of analbuminemia: Essentially

total absence of serum albumin. This is common in pigs,but rare in humans. So far, 18 families with the syndromehave been identified. There is an unexpected paucity ofsequellae from this condition beyond mild edema.2° Thisis perhaps because the small amount of albumin that isavailable has a half-life nearly 10 times the normal andalso because increases in other plasma substances suchas globulins and lipids counter the lack of albumin.The most common exogenously induced albumin var-

iant is bisalbuminemia.7,21 This is transient, nonheredi-tary albumin variant which is present in serum in con-centrations much less than normal albumin. Its produc-tion has been associated with aging, drugs, especially thepenicillins, and pancreatitis.2o

SYNTHESIS OF ALBUMIN AND ITS REGULATION

The serum albumin concentration is the outcome of anumber of processes occurring simultaneously. Theseinclude synthesis and catabolism, which are somewhatindependent. The state of hydration22 and the intravas-cular and extravascular distribution are also importantvariables.Albumin synthesis is unique to the adult liver23 which

normally contains about 750 mg of the newly synthesizedmolecule. The average daily synthesis of 12 to 25 g canaccount for up to 50% of hepatic productive efforts atany one time,24 but less than 10% of the total hepaticanabolic function per day.22 Albumin synthesis consumesabout 6% of daily nitrogen intake.4 4

Only one half to one third of all hepatocytes producealbumin at any one time.6 Polysomes which are boundto the endoplasmic reticulum produce albumin which isexported from the hepatocyte. These are very sensitiveto the concentration of tryptophan.~ Polysomes whichare free within the cytosol of the hepatocyte producealbumin which is needed for intracellular use by thehepatocyte and which is not exported.

In culture, hepatocytes synthesize blood proteins ex-cept albumin at a basal rate. This indicates that regula-tion of albumin production is unlike that of the majorityof other plasma proteins.25 With normal nutrition andhormonal environment, the principal regulator of syn-thesis seems to be the oncotic pressure near the syntheticsite.’ Albumin synthesis is not sensitive to serum levels

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per se, but to the colloidal oncotic pressure near the

synthetic site. This seems to be a property of osmore-ceptors sensitive to the interstitial environment of thehepatocytes. Because of this, albumin synthesis tends tobe reciprocal with that of globulins in serum.4,25,26The hepatic synthetic capacity for albumin depends

upon a complex interaction between the quantity andquality of nutrients, route of intake and the ratio of totalprotein and caloric fuel substances. 17 Caloric deprivationcauses a decrease in the hepatic synthesis of albumin ofas much as 50% within 24 hour1,4,28 and this persists aslong as the deficiency continues. The deficiency statedecreases albumin synthesis out of proportion to totalhepatic protein production, and repletion has a greatereffect on albumin than on other proteins.4°29 The direc-tion of reduction is along the same vector as that ofglycogen removal during fasting: from the portal canalstoward the hepatic venules. 31The mechanism of attenuation of albumin synthesis

depends upon the duration of deprivation. Early duringthe deficiency state, there is disaggregation of free andendoplasmic-bound polysomes. 31,32 This results in a

decrease in the rate of initiation of albumin mRNAtranslation.33 However, there is no major alterationin the hepatocyte content of polysomes or albuminmRNA.32,34,35 Thus, the albumin synthetic system is sus-tained and poised for a rapid recovery. 4,32,35 This is unlikethe situation with other hepatically synthesized proteinsduring states of deprivation.25 This mechanism may becommon to the pathophysiology of decreased albuminsynthesis associated with conditions other than nutri-tional deficiencies.36During the early period of nutritional deficiency, 50 to

90% of the amino acids that go into albumin productionare derived from breakdown of intrahepatic proteins.4 4This is in contrast to other hepatically synthesized pro-teins which are produced from amino acids obtained fromthe catabolism of muscle proteins. During more pro-longed periods of starvation there occurs a reduction inthe number of mRNAs for albumin.44 This mechanismis a slower response to the deprivation and is not rapidlyreversible.33The disaggregation of polysomes and the resulting

decrease in albumin synthesis can be reversed withinminutes by a single feeding of amino acids.31,32 However,not all amino acids have the same capacity to promotethis change. The albumin synthesizing system is verysensitive to tryptophanl and this amino acid seems toplay a special role in enhancing rRNA and mRNA po-lymerases for albumin,31 and thereby albumin mRNAsynthesis.Amino acids other than tryptophan also stimulate

albumin synthesis and these same amino acids also stim-ulate urea production.6,31,3, The urea cycle may have amore important role in normal physiology than onlynitrogen disposal. 32,38 Conversely, the urea cycle may playa role in protein synthesis.1,31,32,38 If albumin synthesis isincreased, urea production is also, and albumin synthesisis reduced when urea synthesis is attenuated. 32.39Although the supply of amino acids to the albumin

synthetic site is important , 40 the energy supply is also

important.’-5 Energy supply may take precedence in thenormal physiology of albumin production. Because ofcompensatory mechanisms noted above, there is little orno change in the amino acid concentration in the inter-stitium or cytosol of the hepatocyte in the fasted or fedstate. So the decrease in albumin synthesis with fastingis not primarily due to decreased availability of aminoacids.35 The refeeding of glucose alone leads to restora-tion of polysome aggregation and albumin synthesis.Therefore, energy rather than amino acid supply moredirectly determines polysome aggregation and conse-quent albumin synthesis under normal circumstances. 15

In addition to nutritional parameters, the hormonalmilieu of the hepatocyte is also important to albuminsynthesis. Cortisone, thyroid hormone, growth hormone,sex hormones, and insulin alter albumin production andtheir effects are additive.1,40 In media devoid of hormones,hepatic synthesis of albumin is decreased remarkablyThis is associated with a decrease in albumin mRNA

indicating decreased transcription of the albumin gene.25Particular hormones may act in other ways. Albumin

synthesis and degradation correlate with thyroid hor-mone levels and plasma T3 is inversely related to plasmaalbumin concentration.¢2 Control of RNA and ribosomalproduction appears to be an important aspect of thy-roidal regulation of albumin synthesis.1,4 Cortisol maypromote binding of ribosomes to endoplasmic reticulum,thus increasing the albumin synthetic rate. Insulin de-ficiency has been associated with decreased albuminproduction,43 but insulin is necessary only for maximaland not basal albumin production,l,4O probably acting byincreasing gene transcription. 18,42,44

RELEASE OF ALBUMIN FROM THE HEPATOCYTE AND

DISTRIBUTION IN THE BODY FLUIDS

The original product of albumin synthesis contains asix amino acid terminus not found on albumin whichcirculates in the blood. This sequence directs albuminfrom ribosomes into secretory pathways and then iscleaved off as one of the last events in albumin produc-tion.’ The parent albumin molecule with the extra aminoacid sequence is found in small amounts in serum espe-cially with rapid albumin production.’ The newly formedalbumin is not stored in the hepatocyte45 but is releaseddirectly into the hepatic interstitium via an energy-dependent process.46 From the interstitium, the albuminmolecules then move into the sinusoid and hepatic ve-nous drainage.47.48 The concentration of potassium in thehepatocyte is important in facilitating release of albuminfrom the hepatocyte into extracellular fluid4°: As theintracellular potassium concentration declines, so doesrelease of albumin from the hepatocyte.~ Hepatic lymphdrainage is not important in the normal flow of newlysynthesized albumin from hepatocyte to circulatingplasma.6,40The newly synthesized albumin becomes part of the

hepatic venous drainage and rapidly distributes through-out the plasma pool, with equilibrium of 90% throughoutthe plasma within 2 minutes or two to three circula-tions.1,4,40 The intravascular space comprises 30 to 40%of the total exchangeable albumin pool,1.’1.40.49..’)(I while the

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extravascular pool makes up the remaining 60 to 70%.The extravascular compartment is composed of twounits, each with its own rate of distribution of intravas-cular albumin into the compartment. 51 One compartmentis made of tissues with discontinuous capillaries such asliver, spleen, and gut and has the more rapid rate ofdistribution with a half-time of 6 hour, and the secondcompartment is composed of tissues with continuouscapillaries such as skeletal muscle and skin and has aslower rate of distribution with a half-time of 28 hour.52Therefore, there are three pharmacokinetic compart-ments of albumin distribution: The intravascular com-

partment and a two-part extravascular compartment.52Because of these dynamics, after the plasma equilib-

rium phase, intravascular albumin equilibrates withinthe extravascular space at a rate of almost 6% perhour.l°4,9°53 Therefore, during health, the plasma half-lifeof infused albumin is about 24 hour.8°55 However, infu-sions of concentrated albumin solutions in normal sub-

jects may increase the transcapillary flux of albumin byas much as 3-fold.56 The extravascular distribution ofalbumin varies among different organs.4° Skin, whichcomposes only 6% of total body weight, contains 11 to18% of the total body albumin 20 and 30 to 40% of thetotal extravascular p001.40,52 In the normal state, skeletalmuscle contains about 15% of the total albumin pool.4°>52Most viscera contain insignificant amounts of exchange-able albumin .40 The liver, the site of albumin production,contains less than 1% of the albumin pool.’ Because ofthis distribution, skin contains 64% of extravascularwater, and skeletal muscle 17%.6 Over one-third of afluid overload can accumulate within these two organswith a paucity of clinical signs.~ The complex distributiondynamics of albumin makes the serum level a poor indi-cator of total albumin stores in the body.52Complete equilibration between the intra- and extra-

vascular albumin pools takes 7 to 10 days.52 Entry ofalbumin into the interstitium is via intracellular vesiclesof the capillary endothelium and this is independent ofwater and ion flow which occurs via interendothelialjunctions .50 The independence of albumin and ion/waterflow allows for a large, stable extravascular mass ofalbumin which can be mobilized into plasma whenneeded there .41,5’ This also makes albumin the majorprotein of edema fluid, composing 1 g/dL of edema ofcardiac, renal, and liver disease, and 2 g/dL in lymphe-dema.’ In many disease states, the normal ratio betweenbody compartments is disrupted, and this alone will

change the serum albumin concentration.22 As an ex-ample, prolonged immobilization increases extravascularalbumin at the expense of intravascular albumin .12 Nor-mally, 80% of the albumin which moves into the inter-stitium returns to the intravascular space via the thoracicduct within 48. 40,57

CATABOLISM OF ALBUMIN

The half-life of albumin is 17 to 19 days,49 and about4% of the exchangeable pool is degraded per day.4’ Al-bumin has a high total catabolic rate in comparison withother plasma proteins, but because of its abundance ithas a low fractional catabolic rate.’ Albumin is degraded

regardless of life span.4° Unlike the situation in whichnutritional intake is normal, during states of caloric andprotein deprivation, exogenously administered albuminmay increase its own catabolism and slow the normalrate of synthesis of albumin by the liver. 4,28,58Albumin synthesis and catabolism are not inter-

dependent4°: One can change without change in theother. Before reaching the catabolic site(s), albumin hasto egress from plasma, and then traverse and equilibratewith an extravascular compartment. Although the exactlocation and nature of the catabolic site(s) are obscure, 41catabolism is receptor independent and not a localizedentity. 40 Probably all organs participate to some extentin total daily catabolism with the normal liver degradingabout 10% of the total catabolic pool.51

CONCLUSIONS

Despite its relatively small size, albumin is one of themost abundant of the plasma proteins. The molecule hasmajor importance in human physiology because of itscolloidal properties, and it plays a less important role inthe acid-base physiology of the human organism. Eachmolecule is composed of three units, or domains, whichfunction together to give the molecule its unique bindingproperties.Albumin is synthesized exclusively by the liver. Its

synthesis depends upon a complex interaction of thenutritional state, the hormonal milieu, and the intersti-tial environment of the hepatocyte. During health,plasma albumin, which composes 30 to 40% of the totalalbumin pool, is maintained at a steady level. The com-plex interactions between the synthesis, distribution, andcatabolism of the molecule have recently begun to unfold.Of these processes, the latter remains the most enig-matic.

REFERENCES

1. Rothschild MA: Albumin synthesis (first of two parts). N Engl JMed 286:748-757, 1972

2. Kao FT, Waskins JW, Law ML, et al: Assignment of the structuralgene coding for albumin to human chromosome 4. Hum Genet62:337-341, 1982

3. Alexander F, Young PR, Tilgham SM: Evolution of the albuminα-fetoprotein ancestral gene from the amplification of a 27 nucleo-tide sequence. J Mol Biol 173:159-173, 1984

4. Rosenoer VM, Oratz M, Rothschild MA (eds): Albumin Structure,Function, and Uses. Pergamon Press, Elmsford, NY, 1977

5. Brown JR: Structural origins of mammalian albumin. Fed Proc35:2141-2144, 1976

6. Tullis JL: Albumin 1: Background and use. JAMA 237:355-359,1977

7. Weitkamp LF: The contribution of variation in serum albumin tothe characterization of human populations. Isr J Med Sci 9:1238-1248, 1973

8. Rothschild MAL Albumin synthesis (second of two parts). N EnglJ Med 286:816-820, 1972

9. Skillman JJ, Parish BM, Tanenbaum BJ: Pulmonary arteriove-nous admixture: Improvement with albumin and diuresis. Am JSurg 119:440-447, 1970

10. Weil MA, Hemming RJ, Puri VK: Colloid oncotic pressure: Clinicalsignificance. Crit Care Med 7:113-116, 1979

11. Granger DN, Galel JC, Drake RE, et al: Physiologic basis for theclinical use of albumin solutions. Surg Gynecol Obstet 146:97-104,1978

at LSU Libraries on November 14, 2014pen.sagepub.comDownloaded from

211

12. Rackowec ED, Falk JL, Fein LA, et al: Fluid-resuscitation incirculatory shock: A comparison of the cardiorespiratory effects ofalbumin, hetastarch and saline solutions in patients with hypovol-emic and septic shock. Crit Care Med 11:839-850, 1983

13. Shoemaker WC: Evaluation of colloids, crystalloids, whole bloodand red cell therapy in the critically patient. Clin Lab Med 2:35-63, 1982

14. White A, Handler, P, Smith EL, et al: Principles of Biochemistry.McGraw-Hill Book Company, New York, 1978

15. Madias NE, Ayuis JC, Adrogue HJ: Increased anion gap in meta-bolic alkalosis. N Engl J Med 300:1421-1423, 1979

16. McAuliffe J, Lind LJ, Leith DE, et al: Hypoproteinemic alkalosis.Am J Med 81:86-90, 1986

17. Nanji AA, Campbell DJL, Pudek MR: Decreased anion gap asso-ciated with hypoalbuminemia and polyclonal gammopathy. JAMA246:859-860, 1981

18. Flaim KE, Hutson SM, Lloyd CE, et al: Direct effects of insulinon albumin gene expression in primary cultures of rat hepatocytes.J Am Physiol Soc 249 (5 part 1):E447-453, 1985

19. Fine JM, Marneux M, Rochu D: Human albumin genetic variants:An attempt at classification of European allotypes. Am J HumGenet 40:278-286, 1987

20. Tarnoky AL: Genetic and drug-induced variations in serum albu-min. Adv Clin Chem 21:101-146, 1980

21. Imai M, Tanase Y, Tokuyuki N, et al: A receptor for polymerizedhuman and chimpanzee albumins on hepatitis B virus particle co-occurring with hepatitis B e antigen. Gastroenterology 76:242-247,1979

22. Karlberg HI, Kern KA, Fisher JE: Albumin turnover in sarcoma-bearing rats in relation to cancer anorexia. Am J Surg 145:95-101,1983

23. Cereghini S, Raymondjean J, Carranca AC, et al: Factors involvedin control of the albumin gene. Cell 50:627-638, 1987

24. Laks H, Pilon RN, Anderson W, et al: Acute normovolemic he-modilution with crystalloid versus colloid replacement. Surg Forum25:21-22, 1974

25. Bjorneboe M, Schwartz M: Investigations concerning the changesin serum proteins during immunization. J Exp Med 110:259-270,1959

26. Rothschild MA, Oratz M, Franklin ED, et al: The effect of hyper-gammaglobulinemia on albumin metabolism in hyperimmunizedrabbits studied with albumin I 131. J Clin Invest 41:1564-1571,1962

27. Smith JE, Lunn PG: Albumin-synthesizing capacity of hepatocytesisolated from rats fed diets differing in protein and energy content.Ann Nutr Metab 28:281-287, 1984

28. Mirtallo JM, Schneider NS, Ruberg RL: Albumin in TPN solu-tions: Potential savings from a prospective review. JPEN 4:300-302, 1980

29. Dionigi RD, Cremaschi RE, Jemos V, et al: Nutritional assessmentand severity of illness classification systems: A critical review ontheir clinical relevance. World J Surg 10:2-11, 1986

30. Lebouton AV: Routine overnight starvation and immunocytochem-istry of hepatocyte albumin content. Cell Tissue Res 227:423-427,1982

31. Rothschild MA, Oratz M, Schreiber SS: Alcohol, amino acids andalbumin synthesis. Gastroenterology 67:1200-1213, 1974

32. Oratz M, Rothchild MA, Shreiber SS: The role of the urea cycleand polyamines in albumin synthesis. Hepatology 4:567-571, 1983

33. Ledford BE, Jacoabs DF: Translation kinetics in cultured mousehepatoma lines. Eur J Biochem 152:611-618, 1985

34. Cassio D, Weiss JC, Oh MO, et al: Expression of the albumin genein rat hepatoma cells and their de-differentiated variants. Cell27:351-358, 1981

35. Princen JMG, Mal-Basks GRB, Yap SH: Restoration effects ofglucose refeeding on reduced synthesis of albumin and total proteinon disaggregated polyribosomes in liver of starved rats: Evidenceof post-transcriptional control mechanism. Ann Nutr Metab27:182-193, 1983

36. Grossman SB, Shafritz DA: Influence of chronic renal failure onprotein synthesis and albumin metabolism in rat liver. J ClinInvest 59:869-878, 1977

37. Oratz M, Schreiber SS, Rothschild MA: Study of albumin synthesisin relation to urea synthesis. Gastroenterology 65:647-650, 1973

38. Rothschild MA, Oratz MD, Schreiber SS: Effects of nutrition andalcohol on albumin synthesis. Alcohol Clin Exp Res 7:28-30, 1983

39. Lescoat L G, Theze N, Fraslin JM, et al: Influence of ornithine onalbumin synthesis by fetal and neonatal hepatocytes maintainedin culture. Cell Differ 21:21-29, 1987

40. Rothschild MA, Oratz M, Schreiber S: Albumin metabolism. Gas-troenterology 64:324-337, 1973

41. Lunn PG, Austin S: Dietary manipulation of plasma albuminconcentration. J Nutr 113:1791-1802, 1983

42. Plant PW, Deeley RG, Grieninger G: Selective block of albumingene expression in chick embryo hepatocyte cultures without hor-mones and its partial reversal by insulin. J Biol Chem 258:15355-15360, 1983

43. Rosso VK, Ware AJ: Cirrhotic ascites: Pathophysiology, diagnosis,management. Ann Intern Med 105:573-585, 1986

44. Flaim KE, Kutson SM, Lloyd CD, et al: Direct effect of insulin onalbumin gene expression in primary cultures of rat hepatocytes. JAm Physiol Soc 9:429-432, 1985

45. Rothschild MA, Oratz M, Schreiber S: Serum albumin. Hepatology8:385-401, 1988

46. Stadhouders AM: Intracellular transport and secretion of proteins.IN Clinical Aspects of Albumin, Yap SH, Majoor CLH, VanTongeren JHM (eds). Martinus Nijhoff Medical Division, TheHague, 1978, pp 9-24

47. Maurice M, Feldmann G, Druet P, et al: Immunoperoxidase local-ization of albumin in hepatocytes of nephrotic rats with specialreference to change in the Golgi apparatus. Lab Invest 40:39-45,1979

48. Peters T Jr, Fleischer B, Fleischer S: The biosynthesis of rat serumalbumin. J Biol Chem 246:240-244, 1971

49. Benotti P, Blackburn GL: Protein and caloric or macronutrientmetabolic management of the critically ill patient. Crit Care Med7:520-525, 1979

50. Rothschild MA, Oratz M, Schreiber SS: Extravascular albumin. NEngl J Med 301:497-498, 1979

51. Yedger S, et al: Tissue sites of catabolism of albumin in rats. AmJ Physiol 244:E101-E107, 1983

52. Jusko WLJ, Gretch M: Plasma and tissue protein binding of drugsin pharmacokinetics. Drug Metab Rev 5:43-140, 1976

53. Dawidson I, Gelin LE, Haglind EP: Plasma volume, intravascularprotein content, hemodynamic and oxygen-transport changes dur-ing intestinal shock in dogs. Crit Care Med 8:73-80, 1980

54. Karanko MS, Laaksonen O, Meratoja OA: Effects of concentratedalbumin treatment after aortocoronary bypass surgery. Crit CareMed 15:727-742, 1987

55. Deysine M, Lieblick N, Aurses AH: Albumin changes during clin-ical septic shock. Surg Gynecol Obstet 137:475-478, 1973

56. Marty AT: Hyperoncotic albumin therapy. Surg Gynecol Obstet139:105-109, 1974

57. Hoye RC, Bennett SH, Geelhoed GW, et al: Fluid volume andalbumin kinetics occurring with major surgery. JAMA 222:1255-1261, 1972

58. Ford EG, Jennings M, Andrassy RJ: Serum albumin (oncoticpressure) correlates with enteral feeding tolerance in the pediatricsurgical patient. J Pediatr Surg 22:597-599, 1987

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