Transcript Systemic Response to Injury and Metabolic Support

Systemic Response to Injury
and Metabolic Support
Aaron Lesher
9/1/09
Definitions
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Infection
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Identifiable source of microbial insult
SIRS
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2 or more of the following:
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Sepsis
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Identifiable source of infection + SIRS
Severe Sepsis
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Temp >38 or <36
HR > 90
RR >20 or PaCO2 <32 or mechanical ventilation
WBC >12,000 or <4000 or >10% bands
Sepsis + organ dysfunction
Septic shock
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Sepsis + cardiovacular collapse (requiring vasopressor
support)
The Systemic Inflammatory Response
Syndrome (SIRS)
CNS regulation of inflammation
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Integral role in inflammatory
response that is mostly involuntary
Autonomic system regulates HR, BP,
RR, GI motility and temp
CNS Regulation of Inflammation
Hormonal Response to Injury
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Includes:
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Cytokines
Glucagon
Insulin
Epinephrine
Serotonin
Histamine
Glucocorticoids
Prostaglandins
leukotrienes
ACTH
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A. Is synthesized in the
hypothalamus
B. Is superceeded by pain, anxiety
and injury
C. Continues to be released in a
circadian pattern in injured patients
D. Causes the release of
mineralocorticoids from the adrenal
in a circadian pattern
ACTH
Cortisol
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Essential for survival during physiologic
stress
Potentiates the effects of glucagon and
epinephrine manifesting as hyperglycemia
In liver, stimulate gluconeogenesis
Induces insulin resistance in skeletal
muscle and adipose tissue
In skeletal muscle induces protein
breakdown and release of lactate
Immunosuppressive agent
A primary action of aldosterone is to:
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A. Convert angiotensinogen to
angiotensin
B. Decrease Cl reabsorption in the renal
tubule
C. Decrease K secretion in the renal
tubule
D. Increase Na reabsorption in the renal
tubule
E. Increase renin release by the
juxtaglomerular apparatus
Catecholamine elevation after injury
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A. Is limited to epinephrine only
B. Is limited to norepinephrine only
C. Increases by 10- to 20-fold after
injury
D. Is sustained 24-48 hours before
decreasing
C-reactive protein
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A. Is secreted in a circadian rhythm
with higher levels in the morning
B. Increases after eating a large
meal
C. Does not increase in response to
stress in patients with liver failure
D. Is less sensitive than ESR as a
marker of inflammation
Mediators of Inflammation
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Cytokines
Heat shock proteins
Reactive oxygen metabolites
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Eicosanoids
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Reperfusion injury
Includes prostaglandins, leukotrienes,
thromboxane
Fatty Acid metabolites
Kallikrien-Kinen system
Serotonin
histamine
Cytokine Response to Injury
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Lots of cytokines
Most potent mediators of
inflammatory response
Pro- and anti-inflammatory
Cytokines….
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TNF-Α
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IL-1
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one of the earliest and most potent mediators of
host response
Primary source: monocytes/macrophages and T
cells
Half life of 20 min but potent
Many functions
Primarily released by macrophages and endothelial
cells
Half life less than 6 mins, “sneaky”
Classic febrile response to injury
IL-6
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Linked to hepatic acute phase proteins production
Impt Eicosanoids
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Prostacyclin (PGI2)
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From endothelium
Decreases platelet aggregation
Promotes vasodilation
Thromboxane (TXA2)
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From platelets
Increases platelet aggregation
Promotes vasoconstriction
Cellular Response to Injury
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Transcription factors impt in
inflammatory response as they
dictate the manner and magnitude
with which a cell can respond to
injury
Endothelium-mediated Injury
L-selectins
Beta 2
integrins
E- or Pselectins
ICAM-1,2
Activated
Neutrophil
Nitric Oxide
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A. Is primarily made in hepatocytes
B. Has a half-life of 20-30 minutes
C. Is formed from oxidation of Larginine
D. Can increase thrombosis in
small vessels
Surgical Metabolism
Basic metabolic needs = 25 kcal/kg/day
Where do we get our caloric needs?
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Fat 9 kcal/g
Protein 4 kcal/g
Oral carbs 4 kcal/g
Dextrose (in IV
fluids) 3.4 kcal/g
Surgical Metabolism
Metabolism during fasting
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Starvation: fat is the main source
of energy in trauma and starvation
Carbohydrates are stored in the
form of glycogen (2/3 skeletal
muscle, 1/3 liver)
Due to deficiency in glucose-6phosphatase, skeletal muscle not
available for systemic use and
therefore, liver stores are used
quickly
Gluconeogenesis
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Occurs in the liver
Precursors include:
Amino acids
(alanine)
 Lactate
 Pyruvate
 Glycerol
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Cori cycle
In late starvation gluconeogenesis
occurs in kidney
Nitrogen wasting during (simple)
starvation
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Sig amounts of protein must be
degraded to be used for
gluconeogenesis
Urine nitrogen excretion increases
from 7-10g/day to up to 30g/day
Protein degradation occurs mostly
in skeletal muscles, but also some
in solid organs
Nitrogen wasting during (prolonged)
starvation
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Systemic proteolysis decreases
Urinary nitrogen approx 2-5g/day
Reflects change to using ketone
bodies as energy source
Brain begins to use ketones as
energy source after 2 days, and this
becomes the principal energy
source by 24 days
Metabolism following Injury
Fat digestion
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Broken down into micelles and FFAs
Micelles enter enterocytes
Chylomicrons are formed which
enter thoracic duct
Medium and short chain amino
acids enter portal system with
amino acids and carbs
Protein Metabolism
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6 g protein = 1 g N
Provides substrates for
gluconeogenesis and acute phase
proteins
1g protein=4kcal
Protein metabolism
Healthy patients undergoing uncomplicated surgery
can remain NPO (with IVF) for how many days
before significant protein catabolism occurs?
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2 days
4 days
7 days
10 days
Healthy patients without malnutrition
undergoing uncomplicated surgery
can tolerate 10 days of partial
starvation before any significant
protein catabolism occurs
Nutrition facts
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Albumin half life = 18 days
Prealbumin = 3 days
Nutrition in the Surgical Patient
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Harris-Benedict equation calculates basal energy
expenditure (nutrition needs) based on weight,
height, age and gender
Usually estimate 30kcal/kg/day
Goals:
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Provide adequate nonprotein calories to prevent
lean muscle breakdown
Meet substrate requirements for protein synthesis
Estimate 1.5-2 g protein/kg/day
Want 100-150 calories of non protein calories for
each 1 g of nitrogen
The nutritionist in the ICU informs you that one of your intubated
patients “Greuner”’s metabolic cart study has revealed a respiratory
quotient of 1.2. What do you do?
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A. Smile. Thank her politely for the information
and run to google.com to figure out what she is
talking about.
B. Ask her to decrease the daily carbohydrates
that the patient is receiving.
C. Ask her to increase the carbohydrate intake.
D. Do nothing, you are tired and the
respiratory quotient is not important in this
patient.
Respiratory Quotient (RQ)
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Ratio of CO2 produced to O2
consumed – measurement of
energy expenditure
RQ>1 = lipogenesis (overfeeding)
RQ<1 = ketosis and fat oxidation
(starving)
Fat RQ = 0.7
Protein RQ = 0.8
Carbohydrate RQ = 1.0
Enteral Nutrition
Does the gut work?
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Yes
Enteral Nutrition
Parenteral Nutrion
PO feeds?
Yes
No
NGT feeds?
No
Yes
Post pyloric feeds
No
Consider G tube
Consider G-J tube
Enteral Nutrition
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Intact GI tract can tolerate complex
solutions
If GI tract has not been fed for a
long period of time, less likely to
tolerate complex carbohydrates
Results in a reduction of infectious
complications in critically ill patients
Which of the following would be typical
of an enteral hepatic-failure formula?
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A. Lower fluid volume, K, PO4, Mag
B. 50% reduction of carbs
C. 50% of proteins are in the form
of branched chain amino acids
(leucine, isoleucine, and valine)
D. Increased arginine, omega 3
fatty acids, and B carotene
Parenteral Nutrition
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Preoperative PN has been shown to be
beneficial to some surgical patients,
especially in those with severe
malnutrition
Postoperatively it is associated with
higher risk of infectious complications
when used inappropriately
Still fewer infectious risks when compared
with no feeding at all
Parenteral Nutrition
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TPN
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Dextrose concentration is high (1525%)
macro- and micronutrients avail via this
route
PPN
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Reduced dextrose (5-10%)
Reduced protein (3%)
Deficiencies
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Chromium 
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Zinc 
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hyperglycemia, neuropathy
Most frequent in pt on PN
Perioral rash
Copper 
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Microcytic anemia
Thanks!
Questions?