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ESPEN Congress Copenhagen 2016

ALBUMIN - A MATTER OF NUTRITION

ALBUMIN METABOLISM DURING INFLAMMATION

B. Soeters (NL)
Albumin metabolism during
inflammation

Peter B. Soeters, the Netherlands


ESPEN congress Copenhagen 2016
Beans et al
Expert Reviews Mol
Medicine
2003 Vol. 5 March

Stages of wound healing:

Trauma/Damage/Disease
Clotting
Early inflammation
Late inflammation:
Growth biomass/cells
Remodeling/strengthening
Beans et al
Expert Reviews Mol Medicine
2003 Vol. 5 March
Under the microscope:
what we see is inflammation
Inflammation
=
Cell proliferation
Matrix deposition
=
Healing
Plasma albumin and inflammation
Which situations are associated with
hypoalbuminaemia?
Is hypoalbuminaemia caused by diminished
synthesis?
Is hypoalbuminaemia caused by an increase in
interstitial space (extravascular extracellular
volume)?
What are the clinical consequences associated
with hypoalbuminaemic states?
Is there a useful purpose served by the state of
hypoalbuminaemia?
33 Anorexia nervosa studies with both
BMI and plasma albumin levels assessed

Lee JL, Oh ES, Lee RW, Finucane TE. Serum Albumin and Prealbumin in Calorically Restricted,
Nondiseased Individuals: A Systematic Review. Am J Med 2015;128:1023 e1-22.
This patient gained 15 kg in the last week. Her plasma albumin
levels amount to 16 g/L. She was healthy not malnourished before
becoming ill. She suffered from severe diverticulitis.
Barac-Nieto, M., et al., Body composition in chronic undernutrition.
Am J Clin Nutr, 1978. 31(1): p. 23-40.
Nutritional compromise was analyzed
based on: Weight/Height, Albumin, CHI

Barac-Nieto, M., et al., Body composition in chronic undernutrition. Am J Clin


Nutr, 1978. 31(1): p. 23-40.
Disproportional decrease in CHI compared to
decrease in BMI => Oedema + low Alb??
Barac-Nieto, M., et al., Body composition in chronic undernutrition. Am J
Clin Nutr, 1978. 31(1): p. 23-40.
Kwashiorkor Marasmus
Hypoalbuminaemia in Kwashiorkor

Jahoor et al, AmJClinNutr 2005;82:792-800


Jahoor et al, AmJClinNutr
2005;82:792-800
Smith, M. I., et al. (2013). "Gut microbiomes of
Malawian twin pairs discordant for
kwashiorkor." Science 339(6119): 548-554.
Stools from discordant twins
(1 kwashiorkor, 1 healthy/marasmus)

Smith, M. I., et al. (2013). "Gut microbiomes of


Malawian twin pairs discordant for
kwashiorkor." Science 339(6119): 548-554.
Endemic malnutrition in adults and
children
Characterized by
Low height (stunting)
Low muscle mass
Very low plasma albumin, when in severe nutritional
compromisein a proportion of individuals
Oedema significant in this last group
Infestation with parasites/ bowel infection/ other
bacterial or candida infections/ changes in
microbiome and metabolites
In marasmus similar infestation/infection but less
oedema and only moderately decreased albumin
levels. Potential role for the microbiome.
Albumin levels
in pathological
states
(Fraction of
normal)

Levitt DG, Levitt MD. Human


serum albumin homeostasis: a
new look at the roles of
synthesis, catabolism, renal and
gastrointestinal excretion, and
the clinical value of serum
albumin measurements.
International journal of general
medicine 2016;9:229-55.
Are growing states associated with
decreased albumin levels?

Control group First trimester Second trimester Third trimester


(N=23) (N=34) (N=35) (N=24) pa

TNF alpha, TGF beta, Interferon gamma:


moderately elevated in healthy pregnancy
strongly elevated in toxicosis and premature child birth

Guven S, Alver A, Mentese A, Ilhan FC, Calapoglu M, Unsal MA. The novel
ischemia marker 'ischemia-modified albumin' is increased in normal pregnancies.
Acta obstetricia et gynecologica Scandinavica 2009;88:479-82.
Breast cancer and hypoalbuminaemia

P F, B S, M K, et al. Evaluation of Glutathione, Albumin and Ascorbic Acid Levels in Breast


Cancer Patients. Int J Clin Med 2013:405-8.
Albumin concentration in plasma

50

40
g/L
30

20

10
Pre-operative Post-operative
Bernadette van Acker, Dept Surgery, Maastricht
FSR Albumin

15
%/day

10

0
Pre-operative Post-operative

Bernadette van Acker, Dept Surgery, Maastricht


Albumin synthesis rates increase!!
1. Cayol M, Tauveron I, Rambourdin F, et al. Whole-body protein turnover
and hepatic protein synthesis are increased by vaccination in man. Clin Sci (Colch)
1995;89(4):389-96.
2. Fearon KC, Falconer JS, Slater C, McMillan DC, Ross JA, Preston T.
Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer
patients with an ongoing acute-phase protein response [see comments]. Ann Surg
1998;227(2):249-54.
3. Jahoor F, Wykes L, Del Rosario M, Frazer M, Reeds PJ. Chronic protein
undernutrition and an acute inflammatory stimulus elicit different protein kinetic
responses in plasma but not in muscle of piglets. J Nutr 1999;129(3):693-9.
4. Barle H, Januszkiewicz A, Hallstrom L, et al. Albumin synthesis in humans
increases immediately following the administration of endotoxin. Clin Sci (Lond)
2002;103(5):525-31.
5. Jahoor F, Abramson S, Heird WC. The protein metabolic response to HIV
infection in young children. Am J Clin Nutr 2003;78(1):182-9.
6. Dahn MS, Mitchell RA, Lange MP, Smith S, Jacobs LA. Hepatic metabolic
response to injury and sepsis. Surgery 1995;117(5):520-30.
Albumin synthesis rates
(normal values mg/kg/day)

Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of
synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of
serum albumin measurements. International journal of general medicine 2016;9:229-55.
Absolute albumin synthesis rates
in liver disease (fraction of normal)

Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of
synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of
serum albumin measurements. International journal of general medicine 2016;9:229-55.
Albumin
synthesis rates
in pathological
states with
healthy livers
(Fraction of
normal)

Levitt DG, Levitt MD. Human


serum albumin homeostasis: a
new look at the roles of
synthesis, catabolism, renal and
gastrointestinal excretion, and
the clinical value of serum
albumin measurements.
International journal of general
medicine 2016;9:229-55.
Albumin kinetics in several disease states
Decreased absolute synthesis rate /BW in:
Liver disease (acute and chronic)
Kwashiorkor (enormous fatty livers)(+ NASH?)
No decrease but rather normal or increased absolute
synthesis rates /BW in:
Most if not all other disease states
Levitt: Albumin kinetics cannot explain low plasma levels
unless clearance is increased (intestinal, renal) ????
Levitt and Levitt do not take into account the increase in
distribution space, which they only consider to be
present in acute situations.
Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of
synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum
albumin measurements. International journal of general medicine 2016;9:229-55.
Fleck A, Raines G, Hawker F, et al. Increased vascular permeability: a major cause of
hypoalbuminaemia in disease and injury. Lancet 1985;1(8432):781-4.
Figure 3. Sequential measurements of excess extracellular water
(ECW) in 8 elderly (open circles)
and 6 young (solid circles) patients with sepsis. Asterisks indicate
significant changes from the preceding measurement.
Adapted from Cheng et al, Arch Surg 1998 133: 745-51
Tipping point:
Spontaneous
rise of:
albumin, urine production,
decrease of:
BW

Hubner M, Mantziari S, Demartines N, Pralong F, Coti-Bertrand P, Schafer M. Postoperative Albumin Drop Is a Marker for
Surgical Stress and a Predictor for Clinical Outcome: A Pilot Study. Gastroenterology research and practice
2016;2016:8743187.
Significance of low plasma albumin
Low plasma albumin is not due to diminished
synthesis
In most disease states absolute synthesis rates
increase
Lower concentrations are due to dilution in a larger
amount of body water outside the cells unless
substantial clearance by gut/kidney
Increases in total body water outside cells are due to
increased capillary escape of fluid, albumin,
electrolytes as an inevitable consequence of
inflammation (compare wound healing)
Therefore low plasma albumin is a sign of the
presence of inflammation
Its course also may reflect rather precisely recovery or
worsening of the disease process
Inflammation (Albumin levels) as predictor of outcome
1. Allen KL, Miskulin D, Yan G, et al. Association of nutritional markers with physical and mental health status in
prevalent hemodialysis patients from the HEMO study. Journal of Renal Nutrition 2002;12(3):160-9.
2. Bruce AC, Erik LP, Louise HB, Carol AP. Protein malnutrition and hypoalbuminemia as predictors of vascular events
and mortality in ESRD. American journal of kidney diseases : the official journal of the National Kidney Foundation 2004;43(1):61-
6.
3. Corti MC, Guralnik JM, Salive ME, Sorkin JD. Serum albumin level and physical disability as predictors of mortality
in older persons. JAMA 1994;272(13):1036-42.
4. Engelman DT, Adams DH, Byrne JG, et al. Impact of body mass index and albumin on morbidity and mortality after
cardiac surgery. J Thorac Cardiovasc Surg 1999;118(5):866-73.
5. Heimann TM, Greenstein AJ, Mechanic L, Aufses AH, Jr. Early complications following surgical treatment for Crohn's
disease. Ann Surg 1985;201(4):494-8.
6. Iwata M, Kuzuya M, Kitagawa Y, Iguchi A. Prognostic value of serum albumin combined with serum C-reactive
protein levels in older hospitalized patients: continuing importance of serum albumin. Aging Clin Exp Res 2006;18(4):307-11.
7. Kudsk KA, Tolley EA, DeWitt RC, et al. Preoperative albumin and surgical site identify surgical risk for major
postoperative complications. Journal of Parenteral and Enteral Nutrition 2003;27(1):1-9.
8. Pifer TB, McCullough KP, Port FK, et al. Mortality risk in hemodialysis patients and changes in nutritional indicators:
DOPPS. Kidney International 2002;62(6):2238-45.
9. Rapp-Kesek D, Stahle E, Karlsson TT. Body mass index and albumin in the preoperative evaluation of cardiac surgery
patients. Clin Nutr 2004;23(6):1398-404.
10. Romagnoni F, Zuliani G, Bollini C, et al. Disability is associated with malnutrition in institutionalized elderly people.
The I.R.A. Study. Istituto di Riposo per Anziani. Aging (Milano) 1999;11(3):194-9.
11. Stenvinkel P, Barany P, Chung SH, Lindholm B, Heimburger O. A comparative analysis of nutritional parameters as
predictors of outcome in male and female ESRD patients. Nephrology, Dialysis, Transplantation 2002;17(7):1266-74.
12. Suttmann U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, Muller MJ. Incidence and prognostic value of
malnutrition and wasting in human immunodeficiency virus-infected outpatients. Journal of Acquired Immune Deficiency Syndrome
and Human Retrovirology 1995;8(3):239-46.
13. Yamamoto T, Allan RN, Keighley MR. Risk factors for intra-abdominal sepsis after surgery in Crohn's disease. Dis
Colon Rectum 2000;43(8):1141-5.
14. Zuliani G, Romagnoni F, Volpato S, et al. Nutritional parameters, body composition, and progression of disability in
older disabled residents living in nursing homes. Journal of Gerontology, Series A: Biological Sciences and Medical Sciences
Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of
synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of
serum albumin measurements. International journal of general medicine 2016;9:229-55.
Plasma albumin and inflammation
Which clinical situations are associated with hypoalbuminaemia?
All inflammatory states (endemic malnutrition, disease, surgery/trauma, infection, growth
(not extensively discussed) = all states where. increased immune cell proliferation and
tissue synthesis are occurring.
Not when exclusively in the presence of a negative nutrient balance).

Is hypoalbuminema caused by diminished synthesis?


No, except partly in liver failure and possibly in Kwashiorkor.

Is hypoalbuminaemia caused by an increase in interstitial space (extravascular


extracellular volume)?
Yes, due to increased membrane permeability and capillary escape of fluid, electrolytes and
proteins, leading to increased extravascular, extracellular volume (oedema): the distribution
space of albumin.

What are the clinical consequences associated with inflammatory/hypoalbuminemic


states?
Diminished capacity to generate an adequate immune/host response to a renewed
challenge (ICU: second hit).
Inflammatory state is a risk in itself

Is there a useful purpose served by increased escape of albumin into the interstitium?
Very likely, not discussed: transporter/regulator, extracellular scavenger and others.
Should we inhibit the inflammatory response?
NSAIDs in acute inflammation
some NSAIDs increase anastomotic leakage after surgery
increase the risk of premature birth/ abortion in pregnancy
aggravate heart failure
induce small bowel lacerations and bleeding
Induce renal failure
NSAIDs in chronic inflammation
Growth:
Increases risk of premature birth
Increases risk of cryptorchism in boys
But: delays early recurrence after primary treatment of breast cancer
Chronic inflammatory disease
Corrects the dysbalance between pro- and anti-inflammatory activity
Severe protracted inflammation due to treatment failure of
primary cause (or due to hyperinflammation):
Kills us