Transcript glut - Pilgrims Hospital

Shiva Sharma
SHO Breast/Endocrine Surgery
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Introduction
Roles of Glutamine in the body
Tissue Protection
Anti-inflammatory regulation
Preservation of metabolic function
Glutamine as therapy
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Leading cause of death in critically ill patients
is sepsis
 230,000 deaths in the USA each year secondary
to sepsis
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Mortality rate from sepsis risen by 90% in last
20years
Development of multi-organ failure
 Organ dysfunction secondary to shock,
inflammation, metabolic disturbances
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Non-essential amino acid
Most abundant AA in the body
 50% free AA in plasma
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Energy source
Precursor to glutathione
 For nucleic acid synthesis
 Anti-oxidant effects
 Used for nitrogen transfer
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Kidney
 Acid-base regulation
 Releases ammonia in urine
 Combines with proton to release bicarbonate into
renal venous bed
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Immune response
 Fuel for monocytes, macrophages, lymphocytes
 Unable to synthesise, rely on plasma glutamine
Roles of Glutamine
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Over last 15-20 years effects of glutamine
studied in ICU setting
Beneficial effects including decreased
morbidity/mortality
Patients in ICU in profound catabolic states
 Release of amino acids from muscle breakdown
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Glutamine however does not increase in
critically ill patients
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Decrease in plasma glutamine observed in
critically ill patients
 Planas M, Schwartz S, Arbos MA, et al: Plasma glutamine levels in septic
patients. JPEN J Parenter Enteral Nutr 1993; 17:299–300
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Low glutamine has also been associated with
increased mortality in ICU patients
 Oudemans-van Straaten HM, et al: Plasma glutamine depletion and
patient outcome in acute ICU admissions. Intensive Care Med 2001;
27:84–90
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Not fully understood
?signalling molecule to regulate gene
expression and intracellular signalling
Stress signal to the body; increase cellular
and immune defence
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Enhancement of Heat Shock Proteins
 These proteins are vital to cellular response to
stresses, and regulate the management of
intracellular proteins
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Wischmeyer etal. performed a series of
experiments in a rat model to show that
glutamine enhanced HSP-70 in septic rats
 Metabolic dysfunction was decreased
 ARDS decreased
 Decreased Mortality
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Ziegler TR etal. also went on to perform a
pilot study; Double blind trial looking at
Glutamine vs Isonitrogenous control solution
in ICU patients on TPN for >5days
Glutamine given as 0.5mg/kg*day
 Showed increase in HSP-70 expression
 Decrease in ICU stay
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Ziegler TR, Ogden LG, Singleton KD, et al: Parenteral glutamine increases
serum heat shock protein 70 in critically ill patients. Intensive Care Med 2005;
31:1079–1086
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Activates peroxisome proliferation activated
receptor-DNA binding sites
 This leads to attenuation of inflammatory
response pathways through inhibitory
transcription factors
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Glutamines acts on NF-kB signalling
pathways
 ?HSP link, as HSP knockout mice loose this
attenuation ability when glutamine administered
after sepsis
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Glutamine decreases insulin resistance
 Reduced hyperglycaemia in ICU patients
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Enhances release of insulin from Beta-cells
Overall improved insulin sensitivity after
administration
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Dechelotte P, et al: L-alanyl-L-glutamine dipeptide-supplemented
total parenteral nutrition reduces infectious complications and
glucose intolerance in critically ill patients: The French controlled,
randomized, double-blind, multicenter study. Crit Care Med 2006;
34:598–604
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Multiple advantages described to support
glutamine administration
Parenteral and enteral supplementation
decrease mortality
REDOXS study looking at glutamines ability
to protect against injury, reduce
inflammation, preserve metabolic function
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Critical Care Connections Inc 2005 (Canadian
Clinical Practice Guidelines) suggest
supplementation of parenteral nutrition with
glutamine and enteral glutamine for
burns/trauma patients
Possible role in patient nutrition
Possible role as prophylaxis in surgery/ICU for
prolonged admissions