ESPEN Congress Copenhagen 2016
Transcript of ESPEN Congress Copenhagen 2016
ALBUMIN METABOLISM DURING INFLAMMATION
B. Soeters (NL)
ESPEN Congress Copenhagen 2016 ALBUMIN - A MATTER OF NUTRITION
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 withhypoalbuminaemia?
• Is hypoalbuminaemia caused by diminishedsynthesis?
• Is hypoalbuminaemia caused by an increase in interstitial space (extravascular extracellularvolume)?
• What are the clinical consequences associatedwith hypoalbuminaemic states?
• Is there a useful purpose served by the state of hypoalbuminaemia?
33 Anorexia nervosa studies with bothBMI 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 albuminlevels amount to 16 g/L. She was healthy not malnourished beforebecoming 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 analyzedbased on: Weight/Height, Albumin, CHI
Barac-Nieto, M., et al., Body composition in chronic undernutrition. Am J ClinNutr, 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, AmJClinNutr2005;82:792-800
Smith, M. I., et al. (2013). "Gut microbiomes of Malawian twin pairs discordant forkwashiorkor." 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 forkwashiorkor." 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.
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 levels in pathological
states(Fraction of
normal)
Are “growing states” associated withdecreased albumin levels?
Control group First trimester Second trimester Third trimester
(N=23) (N=34) (N=35) (N=24) pa
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.
TNF alpha, TGF beta, Interferon gamma:moderately elevated in healthy pregnancystrongly elevated in toxicosis and premature child birth
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
Pre-operative Post-operative
50
40
30
20
10
g/L
Bernadette van Acker, Dept Surgery, Maastricht
FSR Albumin
Pre-operative Post-operative
15
10
5
0
%/day
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 ratesin 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.
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.
Albuminsynthesis ratesin pathological
states withhealthy livers(Fraction of
normal)
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 bepresent 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:Spontaneousrise 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
2001;56(4):M212-6.
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 andtissue 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 (extravascularextracellular volume)?
Yes, due to increased membrane permeability and capillary escape of fluid, electrolytes andproteins, leading to increased extravascular, extracellular volume (oedema): the distributionspace of albumin.
• What are the clinical consequences associated with inflammatory/hypoalbuminemicstates?
Diminished capacity to generate an adequate immune/host response to a renewedchallenge (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?
• NSAID’s in acute inflammation– some NSAID’s 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
• NSAID’s 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