The relationship between serum albumin concentration and sarcopenia

The relationship between The relationship between serum albumin concentration serum albumin concentration

and sarcopenia and sarcopenia

日期： 2013-12-11 報告者：楊柏毅

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Outline Introduction Albumin metabolism Disturbances in serum albumin Sarcopenia and skeletal muscle proteins Recent studies about hypoalbuminemia and

sarcopenia Albumin kinetics in hepatic disease Albumin kinetics in renal disease Conclusions 2

Introduction(1) Albumin

The gene located on chromosome 4

A single polypeptide chain of 585 amino acid residues and contains 17 disulfide bonds, molecular weight of 67 kDa

The half-life is 19 days 3

Introduction(2) The most abundant plasma protein, about

50%, responsible for 75~80% of the colloid osmotic pressure(COP, 25–33mm Hg)

Predominantly synthesized by the liver 10~50% of liver protein synthesis 10~15g is produced per day in healthy

subjects

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Introduction(3) A negative acute-phase protein

Acute-phase proteins The plasma concentrations changes in response to

inflammation

Positive acute-phase proteins Serve part of the innate immune system C-reactive protein, fibrinogen( 纖維蛋白元 ),

ferritin( 儲鐵蛋白 ) Negative acute-phase proteins

To save amino acids Albumin, transferrin( 運鐵蛋白 ) 5

Introduction(4) Serum albumin

concentration(3.2~3.5~5~5.4 g/dL) The result of

Synthesis, catabolism Variations in the intra/extravascular distribution The hydration state

Constant over time, daily variation 2.5~3% Reflects the intravascular portion of the pool,

about 40% of the total The extravascular portion － 60% of total The total albumin － 200 g 6

Introduction(5) 2 components of the extravascular pool

Faster(half-life: 6h) － in organs with discontinuous capillaries (liver, spleen, gut)

Slower(half-life: 28h) － in organs with continuous capillaries (mainly skeletal muscle and the skin)

The skin － 11~18%, the muscle － 15%, the liver － 1% of total albumin

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Introduction(6) Important functions of albumin

Mediating blood volume, colloid osmotic pressure (COP), blood PH

Binding, transport, distribution and metabolism of metals, hormones, ligands( 配體 ), therapeutic drugs and metabolites

Significantly alter the half-life, distribution and metabolism of drugs

A carrier of nitrogen from visceral (i.e. the liver) to peripheral (i.e. muscle) organs 8

Albumin metabolism(1) Synthesis by the

ribosome Secretion pathway-

30mins Secreted into the

bloodstream Less than 2 g is

stored within the liver 9

Albumin metabolism(2) Synthesis rate is regulated

The oncotic pressure at the hepatocyte, the extracellular albumin concentration

Nutritional dependency The meal of amino acids(6% of the daily nitrogen

intake), the post-prandial insulin increase Greater effects than other proteins Specific amino acids such as tryptophan(色酸氨 )

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Albumin metabolism(3) Synthesis rate is regulated

By hormones (cortisone, thyroid hormones, insulin, growth hormone, sex hormones)

Inflammation Down-regulate albumin synthesis Total liver protein synthesis (mostly acute phase

proteins) was increased

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Albumin metabolism(4) The factors that regulate albumin

degradation are not clearly established Liver － 15% Kidneys － 10% Muscle, liver and kidney are the main

contributors to albumin catabolism (40–60%)

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Lower serum albumin An indicator for clinical outcome in healthy

elderly subjects and in renal disease Poor functional status in older persons, even

among nondisabled older persons

(Goldwasser P et al. 1997; Weijenberg MP et

al. 1997; Corti MC et al.1994)

Disturbances in serum albumin(1)

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Disturbances in serum albumin(2) The Zutphen Elderly Study

(Weijenberg MP et al. 1997) Serum albumin concentration of 2.5 g/dL

Predicts coronary heart disease Increase all-cause mortality in elderly men

The benefit of a high albumin concentration

(Corti et al. 1994)

>4.3 g/dL related to reduced mortality of 20–40% in elderly compared to 4.1–4.3 g/dL

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Disturbances in serum albumin(3) Low serum albumin occur in

Malnutrition: unintentional weight loss > 10% and serum albumin level < 3.2 g/dL

Malabsorption Liver disorders Cancer Sepsis Renal disease Burn Pregnancy decreases 0.5~0.8 g/dL 15

Disturbances in serum albumin(4) A slight increase in serum albumin

Dehydration or significant fluid loss Sunstroke Exercising strenuously

Hyperalbuminemia (serum albumin >5.5 g/dL) is extremely rare

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Sarcopnia and skeletal muscle proteins(1)

Sarcopenia Age-associated loss of skeletal muscle mass

and function Causes

Multifactorial, include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies

Diagnosis Gait speed <1 m/s and low muscle mass (eg,

appendicular mass relative to height2 that is ≤ 7.23 kg/m2 in men and ≤ 5.67 kg/m2 in women 17


Muscle Approximately one half of body proteins Changes in muscle mass←→ Body protein

content/metabolism Affecting strength, muscle functions, control

of posture

Muscle protein turnover is slow ( 2% per ≦day), changes in muscle mass reflect long-term alterations in muscle metabolism

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The muscle mass is the result of

(Wolfe RR 2001; Lang CH et al. 2002) Muscle protein synthesis

Hyperaminoacidemia, hyperinsulinemia Growth hormone, insulin-like growth factor

1(IGF-1) Exercise

Muscle protein degradation Inhibited by insulin and amino acids

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Recent studies about Recent studies about hypoalbuminemia and sarcopenia(1)hypoalbuminemia and sarcopenia(1)

Significant The Health, Aging and Body Composition

Study (Health ABC)

(Visser M et al. 2005) The Longitudinal Aging Study Amsterdam

(LASA)

(Schalk et al. 2005)

Trend, but inconsistent or insignificant The Osteoporotic Fractures in Men Study

(MrOS) (Caryn KS et al. 2012) 20


Participants Measurement Period

Health ABC

1882 black and white men and women, aged 70–79y, no difficulty walking one-quarter of a mile or climbing 10 steps without resting

Serum albumin at baselineAppendicular skeletal muscle mass(ASM)Total-body fat-free mass(FFM)Trunk lean mass (TLM)

5y

LASA 676 women and 644 men aged 65~88y

Serum albumin at baselineGrip strength

Baseline, 3y,6y

MrOS 5229~1267 community-dwelling (primarily white)men 65y, able to ≧walk without the assistance of another person and had at least one native hip

Serum albumin at baseline and 2yAppendicular skeletal muscle mass(ASM)Grip strengthLeg power

Baseline, 2y, 4.6y

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Other covariates or confounders Demographic factors, medical history,

medication use, alcohol consumption, smoking status

Physical activity level Weight training Total caloric intake and protein intake Inflammatory markers

Interleukin 6 (IL-6) and C-reactive protein (CRP)

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The Health ABC Study(1)The Health ABC Study(1)

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The Health ABC Study(5) Lower serum albumin in older persons was

associated with a greater loss of ASM during a 5y follow-up

Lower serum albumin concentrations, even >3.8 g/dL, are associated with future loss of ASM

Low serum albumin may be a risk factor for sarcopenia

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The LASA Study(1)The LASA Study(1)

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The LASA Study(3)

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The LASA Study(5)

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The LASA Study(7) Lower serum albumin was associated with

weaker muscle strength Lower serum albumin was associated with

greater decline in muscle strength over 3y Low serum albumin, even within the

normal range, is independently associated with weaker muscle strength and future decline in muscle strength in older women and men 34

The MrOS Study(1) Men who died or voluntarily withdrew (n =

603) or who did not participate in Visit 2 (n = 749) Older at baseline Serum albumin <4.0 g/dL at baseline Lower baseline grip strength and leg power

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The MrOS Study(2)The MrOS Study(2)

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The MrOS Study(3)The MrOS Study(3)

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The MrOS Study(4) Although a statistically significant trend

was observed between serum albumin change and changes of ASM and leg power (P <0 .03), there was substantial overlap in the CIs across categories

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The MrOS Study(5) Serum albumin demonstrated modest and

inconsistent trends with loss of muscle mass and function

Low serum albumin within the normal range is not a risk factor for this process in elderly men

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Discussion about controversy(1) The MrOS Study may appear to

contradict past research findings, but the magnitude of change is similar Mean change of ASM mass The difference in mean ASM mass change

between the highest and lowest serum albumin categories

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Discussion about controversy(2) Differences in analysis methods

The analysis of data from the LASA used a one-sided, trend P-value, can result in smaller P-values than the two-sided P-value in the MrOS study

Large sample sizes result in associations that are small in magnitude with highly statistically significant P-values

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Discussion about controversy(3) The potential bias in the MrOS study

Participants who died, voluntarily withdrew, or did not participate were more likelySerum albumin <4.0 g/dLLower grip strength and leg power

Primarily white men, and the results may not be generalizable to women or other racial groups

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Discussion about controversy(4) The results of available literature are not

compelling and do not support the use of serum albumin as a risk factor for sarcopenia

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Albumin kinetics in hepatic disease(1)

Measure 1 point 2 points 3 points

Total bilirubin, μmol/l (mg/dL)

<34 (<2) 34-50 (2-3) >50 (>3)

Serum albumin, g/dL

>3.5 2.8-3.5 <2.8

PT INR <1.7 1.71-2.30 > 2.30

Ascites None MildModerate to Severe

Hepatic encephalopathy None

Grade I-II (or suppressed with medication)

Grade III-IV (or refractory

The Child-Pugh score

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Points ClassOne year survival

Two year survival

5-6 A 100% 85%

7-9 B 81% 57%

10-15 C 45% 35%

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Albumin synthesis in liver cirrhosis Correlates directly with the Child–Pugh

classification Maybe normal in Child A p’ts Decreased in Child B and C p’ts Correlates with the galactose(半乳糖 )

elimination capacity and the aminopyridine test

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Albumin synthesis in liver cirrhosis

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Albumin kinetics in renal disease Albumin metabolism

In the nephrotic syndrome In end stage renal disease(ESRD, just before

dialysis) In peritoneal dialysis (PD) In hemodialysis (HD)

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Albumin metabolism in the nephrotic syndrome(1)

The nephrotic syndrome is characterized by Proteinuria ( 3.5 g/day)≧

Mostly albuminuria Increased permeability of the glomerular capillary to

plasma proteins

Hypoalbuminemia Edema Hyperlipidemia

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Adaptive responses to albumin loss From extravascular albumin pool to the

intravascular pool － limited value, more depleted

Increased albumin catabolism, 95% of the filtered albumin is reabsorbed and catabolized in the kidney

Upregulation of albumin synthesis to 145~200%

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Fibrinogen Hepatic-derived protein Increased synthysis and elevated in the

nephrotic syndrome Contribute to thrombosis and coronary artery

disease (CAD)

A strong correlation for the incresed synthysis of albumin, fibrinogen and transferrin

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Albumin metabolism in ESRD(just before dialysis)

Normal catabolism, small increased(20%) or normal albumin synthysis

Serum albumin normal, despite significant albumin loss in urine

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Albumin metabolism in PD(1) Normal catabolism, but

albumin loss during PD Albumin synthysis

increased(135%), but unable to higher levels

Serum albumin decreased A correlation between total

albumin loss and serum albumin

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Albumin metabolism in PD(2) The mechanisms of protein loss during PD

Albumin shift from extravascular sites adjacent to the peritoneum

Direct passage of albumin from blood stream to peritoneal cavity

Tendency of the inter-dialysis peritoneal fluid to equilibrate with plasma proteins

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Albumin metabolism in HD(1) No protein loss, normal

albumin catabolism Normal serum albumin Increased albumin

synthysis Albumin synthysis

correlated positively with plasma volume

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Albumin metabolism in HD(2) Causes of hypoalbuminemia in HD p’ts

The acute-phase response decrease albumin synthysis and increase catabolism

(Kaysen et al. 2002)Long-lived acute-phase proteins(ceruloplasmin or α1-acid glycoprotein) correlated positively with albumin FCR

Blood volume is expanded57

Albumin metabolism in HD(3) Hyperfibrinogemia

Observed as well in ESRD and dialysis p’ts Associated with an increased prevalence of

coronary heart disease (CHD) Resulted from increased synthesis alone A strong correlation was observed for

albumin and fibrinogen synthysis in dialysis p’ts

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Conclusion(1) The limited effect of muscle strengthening

exercise on the hypoalbuminemic p’ts Malnutrition: unintentional weight loss > 10%

and serum albumin level < 3.2 g/dL Liver disorders Renal disease Cancer Sepsis

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Conclusion(2) Early mobilization is still important

Mobilize secretions, improve lung hygiene and expansion

Prevent postural hypotention, normalize blood volume distribution, maintain cardiovascular function

Prevent ileus and postural hypotention

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Reference(1) Berthil H.C.M.T. Prinsen, Monique G.M. de Sain-van der

Velden. Albumin turnover: experimental approach and its application in health and renal diseases. Clinica Chimica Acta 2004; 347: 1–14.

Paolo Tessari. Protein metabolism in liver cirrhosis: from albumin to muscle myofibrils. Current Opinion in Clinical Nutrition and Metabolic Care 2003; 6: 79–85.

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Reference(2) Visser M, Kritchevsky SB, Newman AB et al. Lower

serum albumin concentration and change in muscle mass: The Health, Aging, and Body Composition Study. Am J Clin Nutr 2005;82:531–537.

Schalk BW, Deeg DJ, Penninx BW et al. Serum albumin and muscle strength: A longitudinal study in older men and women. J Am Geriatr Soc 2005;53:1331–1338.

Caryn KS, Jodi AL, Peggy MC et al. Serum Albumin in Relation to Change in Muscle Mass, Muscle Strength, and Muscle Power in Older Men. J Am Geriatr Soc 2012; 60: 1663–1672.

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The relationship between serum albumin concentration and sarcopenia

Health & Medicine

Transcript of The relationship between serum albumin concentration and sarcopenia