Systemic Response to Injury & Metabolic Support

a review of Schwartzs Principles of Surgery- Chapter 1 Anas MK hindawi PG1 MGH straight intern 21/6/2012

Introduction

Inflammatory response to injury

Local- limited duration, restores function Major

Clinical Spectrum of SIRS

Infection

Sepsis

Identifiable source of microbial insult

Infection + SIRS

SIRS = 2 or more:

Severe Sepsis

Sepsis + Organ Dysfunction

Temp 38C or 36C HR 90 bpm RR 20 breaths/min or PaCO2 32 mmHg or mechanical ventilation WBC 12,000/L or 4000/L or 10% band forms

Septic Shock

Sepsis + Cardiovascular Collapse (requires vasopressors)

Signaling

Humoral inflammatory mediators in the circulation can induce fever and anorexia i.e. TNF- Neural parasympathetic vagal stimulation attenuates the inflammatory response via Ach release

Reduces HR, increases gut motility, dilates arterioles, constricts pupils, and decreases inflammation Reduces macrophage activation Reduces macrophage release of pro-inflammatory mediators (TNF-, IL-1, IL-18)

Hormone Signaling

Hormone classifications
polypeptide (cytokine, insulin) amino acid (epinephrine, serotonin, or histamine) fatty acid (cortisol, leukotrienes)

Pathways
Receptor Kinases insulin Guanine nucleotide binding (G-protein) - prostaglandins Ligand Gated ion channels

Adrenocorticotropic Hormone

Synthesized anterior pituitary Regulated by circadian signals Pattern is dramatically altered in injured patients Elevation is proportional to injury severity Released by: pain, anxiety, vasopressin, angiotensin II, cholecystokinin, catecholamines, and pro-inflammatory cytokines ACTH signals increase glucocorticoid production

Glucocorticoids

Cortisol elevated following injury,

duration of elevation depends on severity of injury

Potentiates hyperglycemia
Hepatic gluconeogenesis Muscle and adipose tissue > induces insulin resistance Skeletal m.> protein degradation, lactate release Adipose -> reduces release of TG, FFA, glycerol

Exogenous administration

Adrenal suppression in the acutely ill

Acute Adrenal Insufficiency Atrophy of the adrenal glands Weakness, n/v, fever, hypotension Hypoglycemia, hyponatremia, hyperkalemia
Thymic involution, decreased T-killer and NK fcn, graft vs host rxns, delayed hypersensitivity responses, inability of monocyte intracellular killing, inhibition of superoxide reactivity and chemotaxis in neutrophils Down regulates pro-inflammatory cytokine production (TNF, IL-1, IL-6) Increases anti-inflammatory mediator IL-10 Useful in septic shock, surgical trauma, and CABG

Immunosuppression

Macrophage Inhibitory Factor

Glucocorticoid antagonist produced by anterior pituitary & T-lymphocytes Reverses immunosuppressive effects of glucocorticoids Potentiates G- and G+ septic shock Experimentally improves survival

Growth Hormone

During stress -> protein synth, fat mobilization, and skeletal cartilage growth 2 to release of insulin-like growth factor (IGF1) Injury reduces IGF1 levels IGF1 inhibited by pro-inflammatory cytokines

TNF-, IL-1, IL-6

GH admin to pediatric burn patients shows improvement in their clinical course

Catecholamines

Severe injury activates the adrenergic system Norepi and Epi immed. increase 3-4 fold and remain elevated 24-48hrs after injury Epinephrine
hepatic glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis Decreases insulin and glucagon secretion Peripheral- lipolysis, insulin resistance in skeletal m. = stress induced hyperglycemia

Epinephrine other effects

Increase secretion of T3, T4, and renin Reduces release of aldosterone Enhances leukocyte demargination and lymphocytosis

Aldosterone

Synthesized, stored, released from the adrenal zona glomerulosa Maintains intravascular volume
Conserves sodium Eliminates potassium and hydrogen ions Acts on the early distal convoluted tubules

Deficiency- hypotension, hyperkalemia Excess- edema, HTN, hypokalemia, metab alkalosis

Insulin

Hyperglycemia and insulin resistance are hallmarks due to the catabolic effects of circulating mediators Hyperglycemia during critical illness has immunosuppressive effects Injury has 2 phases of insulin release Within hours- release is suppressed Later- normal/xs insulin production with peripheral insulin resistance Tight control of glucose levels esp. in diabetics significantly reduces mortality after injury

Acute Phase Proteins

Nonspecific markers Produced by hepatocytes Response to injury, infection, inflammation C-reactive protein best reflects inflammation
No diurnal variation, not affected by feeding Affected only by hepatic insufficency

Inflammatory Mediators

Heat Shock Proteins Reactive Oxygen Metabolites Eicosanoids Fatty Acid Metabolites Kallikrein-Kinin System Serotonin Histamine Cytokines

Heat Shock Proteins

Induced by burn injury, inflammation, and infection HSPs bind autologous and foreign proteins and function as intracellular chaperones for ligands such as bacterial DNA and endotoxin Requires gene induction by a transcription factor Production seems to decline with age

Reactive Oxygen Metabolites

Short-lived Cause tissue injury by oxidation of unsaturated fatty acids within cell membranes Produced by anaerobic glucose oxidation and reduction to superoxide anion in leukocytes Further metabolized to hydrogen peroxide and hydroxyl radicals Cells are protected by oxygen scavengers glutathione and catalases In ischemia- production of oxygen metabolites are activated but nonfunctional due to no oxygen supply. After reperfusion, large amounts are produced causing injury

Eicosanoids

Eicosanoids

derived primarily by oxidation of the membrane phospholipid arachidonic acid Induced by hypoxic injury, direct tissue injury, endotoxin, norepinephrine, vasopressin, ang II, bradykinin, serotonin, ACh, cytokines, histamine systemic effects : neurotransmission, vasomotor regulation, and immune cell regulation Generate proinflammatory response Adverse effects include acute lung injury, pancreatitis, renal failure NSAIDs ,steroids and leukotriene inhibitors block the end products of eicosanoid pathways

Eicosanoid Effects

Pancreas glucagon secretionPGD2, PGE2 while Insulin secretion by HPETE Liver glucagon stimulated glucose production- PGE2 Adipose lipolysis- PGE2 Bone resorption- PGE2, PGF2, PGI2 Parathyroid PTH secretion- PGE2 Pulmonary BronchoconstrictionPGF2, TXA2, LTC4, LTD4, LTE4 Immune suppress lymphocytesPGE2

Hematologic

platelet aggregation- TXA2

Pituitary

Prolactin- PGE1 LH- PGE1, PGE2, 5-HETE TSH- PGA1, PGB1, PGE1, PGE1 GH- PGE1

Renal renin secretion- PGE2, PGI2 GI cytoprotective- PGE2

Leukotrienes are potent mediators of capillary leakage as well as leukocyte adherence, neutrophil activation, bronchoconstriction, and vasoconstriction Cyclooxygenase pathway products inhibit pancreatic B-cell release of insulin, whereas lipoxygenase pathway products stimulate B-cell activity. Human sepsis trials have failed to show a mortality benefit of inhibiting eicosanoid pathway by using NSAIDs

Fatty Acid Metabolites

Omega 6 FA precursors of inflammatory mediators (LT, PG, platelet activating, factor) Substituting Omega 3 FA attenuate the inflammatory response Reduces TNF, IL6, PGE2 ,NF b attenuates weight loss, increase small-bowel perfusion, and may increase gut barrier protection preoperative supplementation with omega-3 fatty acid was associated with reduced need for mechanical ventilation, decreased hospital length of stay, and decreased mortality with a good safety profile

Kallikrein-Kinin System

Bradykinins are potent vasodilators Stimulated by hypoxic and ischemic injury

Hemorrhage, sepsis, endotoxemia, tissue injury Magnitude proportional to severity of injury

Produced by kininogen degradation by kallikrein Kinins increase capillary permeability (edema), pain, inhibit gluconeogenesis, renal vasodilation, incr bronchoconstriction In clinical trials, bradykinin antagonists help reverse Gsepsis, but do not improve survival

Serotonin

Present in CNS neurons , intestinal chromaffin cells & platelets Vasoconstriction, bronchoconstriction, platelet aggregation Myocardial chronotrope and ionotrope Unclear role in inflammation

Histamine

Stored in neurons, skin, gastric mucosa, mast cells, basophils, and platelets H1 bronchoconstriction, increases intestinal motility and myocardial contractility , vasodilation H2 stimulates gastric parietal cell acid secretion H3 is an autoreceptor found on presynaptic histamine-containing nerve endings and leads to downregulation of histamine release H4 is expressed primarily in bone marrow, eosinophils, and mast cells

Cytokines

Most potent mediators of inflammation Local- eradicate microorganisms, promote wound healing Overwhelming response- hemodynamic instability (septic shock) or metabolic derangements (muscle wasting) Uncontrolled- end-organ failure, death Self-regulatory production of anti-inflammatory cytokines, but inappropriate release may render the patient immunocompromised and susceptible to infection

Tumor Necrosis Factor

Secreted from monocytes, macrophages, Tcells Potent evocation of cytokine cascade Induces muscle catabolism/cachexia, coagulation, PGE2, PAF, glucocorticoids, eicosanoids Circulating TNF receptors compete with cellular receptors and may act as a counter regulatory system to prevent excessive TNF- activity

Interleukin-1

Released by activated macrophages, endothelial cells IL1- cell membrane associated IL1- circulation 2types of receptors same as TNFRs mech. Synergistic with TNF- T = 6 min Induces febrile response by stimulating PG activity in the anterior hypothalamus

Interleukin-2

Promotes T-lymphocyte proliferation and differentiation, Ig production, gut barrier integrity T < 10 min Major injury or perioperative blood transfusions reduce IL-2 activity leading to a transient immunocompromised state Its blockade used pharmacologically in organ transplantation

Interleukin-4

Produced by type 2 T Helper lymphocytes Important in antibody-mediated switching and antigen presentation Induces class switching to promote IgE & IgG4

Important in allergic and antihelmintic responses

Anti-inflammatory- downregulates IL-1, TNF-, IL-6, IL-8 and oxygen radical production Increases macrophage susceptibility to antiinflammatory effects of glucocorticoids

Interleukin-6

Induced by IL-1 and TNF- Levels are detectable within 60 min of injury, peak 4-6 hours, and persist up to 10 days Levels are proportional to extent of tissue injury High plasma IL-6 levels have been associated with mortality during intra-abdominal sepsis Anti-inflammatory

Attenuate TNF- and IL-1 activity Promote release of circulating TNF- receptors & IL-1 antagonists stimulates the release of cortisol

Interleukin-8

Released from macrohages andd endothelial cells mainly Chemoattractant for neutrophils Stimulates release of IFNpLasma levels are associated with disease severity

Interleukin-10

Anti-inflammatory Released from monocytes Down-regulates TNF- activity Increased plasma levels of IL-10 have been associated with mortality and disease severity after traumatic injury significantly contribute to the underlying immunosuppressed state during sepsis

Interleukin-12

Promotes differentiation of type 1 T Helper cells so known as regulator cell mediated Released by activated phagocytes, including monocytes, macrophages, neutrophils, and dendritic cells IL-12 stimulates lymphocytes to increase secretion of IFN- with the costimulus of interleukin-18 stimulates natural killer cell cytotoxicity and helper T cell differentiation IL-12 enhances coagulation as well as fibrinolysis

Interleukin-13

Similar to IL-4, overall anti-inflammatory Modulates monocytes function Unlike IL-4, has no effect on T lymphocytes Inhibits pro-inflammatory cytokines Attenuates leukocyte interaction with activated endothelial surfaces

Interleukin-15

Derived from macrophages mainly functions as a regulator of cellular immunity Shares receptor components with IL-2, and shares promoting lymphocyte activation/prolif. acts as a potent inhibitor of lymphocyte apoptosis

Interleukin-18

Formerly IFN--inducing factor Produced by macrophages Pro-inflammatory, similar to IL-12 Increased levels are pronounced (especially in G- sepsis) IL-18 regulation is in part mediated through IL18binding protein (IL-18BP) which found to be secreted also by molluscum contagiosum skin Pathogen

Interferon-

Helper T lymphocytes activated by bacterial antigens, IL-2, IL-12, or IL-18 produce IFN- IFN- can induce IL-2, IL-12, or IL-18 Detectable in circulation by 6 hrs and remain elevated for up to 8 days Activate circulating and tissue macrophages Induces acute lung inflammation by activating alveolar macrophages after surgery or trauma Negative regulators of IFN- include IL4, IL-10, and glucocorticoids

Granulocyte-Macrophage ColonyStimulating Factor

upregulates both granulocyte and monocyte cell lines from hematopoietic bone marrow stem cells Delays apoptosis of macrophages and PMNs Promotes the maturation and recruitment of PMNs in inflammation potentiate acute lung injury during critical illness

High Mobility Group Box 1

DNA transcription factor Expressed 24-48 hrs after injury Associated with weight loss, food aversion, shock, SIRS and Sepsis Peak levels are associated with ARDS and death

Cell Signaling Pathways

Heat Shock Proteins

Ligand Gated Ion Channels

Cell Signaling Pathways

G-protein receptors

Largest family of signaling receptors Adjacent effector protein activated receptor Second messengers cAMP or calcium Can result in gene transcription or activation of phospholipase C
When activated, receptors dimerize, phosphorylate, and recruit secondary signaling molecules Used in gene transcription and cell proliferation by mean of cell signaling for several growth factors i.e. insulin, PGDF, IGF-1

Tyrosine Kinases

Cell Signaling Pathways

Janus Kinase/Signal Transduction and Activator of Transcription (JAK-STAT)

IL-6, IL-10, IL-12, IL-13, IFN- Ligand binds to the receptor, receptor dimerizes, enzymatic activation via phosphorylation propagates through the JAK domain and recruits STAT to the cytosolic receptor portion. STAT dimerizes and translocates into the nucleus as a transcription factor within minutes of JAKs binding to cytokines Suppressors of cytokine signaling (SOCS) block JAK-STAT

Mitogen-Activated Protein Kinases

(MAPK) pathway is a major cellular inflammatory signaling pathway with regulatory roles over cell proliferation and cell death MAPK isoforms exhibit appreciable crosstalk, which can modulate the inflammatory response

Nuclear Factor-B

NF-B activates genes important for the activation of proinflammatory cytokines and acute phase proteins Cytosolic NF-B is maintained by binding to the inhibitor protein I-B Low intracellular I-B appears to prolong the inflammatory response and enhanced activity of NF-B appears to delay the apoptosis of activated immune cells

Toll-Like Receptors and CD14

Lipopolysaccharide (LPS), an endotoxin, is an important mediator of gramnegative sepsis syndrome TLR4 is primarily the receptor for gram-negative endotoxins and TLR2 is the counterpart for gram-positive sepsis Specific point mutations in the TLR gene change susceptebility for infections among patients

Tumor Necrosis Factor

Apoptosis - normal fcn of cellular disposal w/o activating the immune/inflammatory system 2 receptors
TNFR-1 : inflammation, apoptosis, circulatory shock TNFR-2 : no inflammation or shock

CD95 (Fas) receptor similar structure to TNFR-1

Initiates apoptosis

Cell Mediated Inflammation

Platelets

Source of eicosanoids and vasoactive mediators Clot is a chemoattractant for PMNs/monocytes Modulate PMN endothelium adherence Migration occurs within 3 hrs of injury

Mediated by serotonin, PAF, PGE2

Eosinophils

Migrate to parasitic infection and allergen challenge to release cytotoxic granules Reside in the GI, lung, and GU tissues Activated by IL-3, GM-CSF, IL-5, PAF, and anaphylatoxins C3a and C5a

Cell Mediated Inflammation

Lymphocytes

T-helpers produce IL-3, TNF-, GM-CSF

TH1: IFN-, IL-2, IL-12 TH2: IL-4, IL-5, IL-6, IL-9, IL-10, IL-13 Severe infection shift toward more TH2

Mast Cells

First responders to injury Produce histamine, cytokines, eicosanoids, proteases, chemokines, TNF- (stored in granules) Cause vasodilation, capillary leakage, and recruit immunocytes

Cell Mediated Inflammation

Monocytes

Downregulation of receptor TNFR is clinically and experimentally correlated with CHF, nonsurvival in sepsis Modulate acute inflammation Maturation is stimulated by G-CSF Rolling (L-selectin (fast), P-selectin (slow) Adhesion/transmigration ICAM 1, 2, PECAM 1, VCAM 1, CD18

Neutrophils

Endothelium-Mediated Injury

Neutrophil-Endothelium Interaction
Increased vascular permeability facilitate oxygen delivery and immunocyte migration Accumulation of neutrophils at injury sites can cause cytotoxicity to vital organs Ischemia-reperfusion injury potentiates this response by releasing oxygen metabolites and lysosomal enz.

Nitric Oxide

Derived from endothelial surfaces responding to Ach, hypoxia, endotoxin, cellular injury, or shear stresses of circulating blood T = seconds Reduces microthrombosis, mediates protein synthesis in hepatocytes Formed from oxidation of L-arginine via NOS

Prostacyclin (PGI2)

Endothelium derived in response to shear stress and hypoxia Vasodilator Platelet deactivation (increases cAMP) Clinically used to reduce pulmonary hypertension (especially pediatric)

Endothelins

Produced as a response to a variety of factors injury, anoxia, thrombin, IL-1, vasopressin ET-1 is a potent vasoconstrictor, 10x more potent than angiotensin II Works in synergism with NO acc. To vascular smooth muscle tone

Platelet Activating Factor

Phospholipid component of cell membranes, constitutively expressed at low levels Released by PMNs, platelets, mast cells, monocytes during acute inflammation Further activates PMNs and platelets Increases vascular permeability PAF antagonists reduce ischemia/reperfusion injury

Metabolism During Fasting

Comparable to changes seen in acute injury Requires 25-40 kcal/kg/day of carbs, protein, fat Normal adult body contains 300-400g carbs (glycogen) 75-100g hepatic, 200-250g muscle (not available systemically due to deficiency of G6P)

Mass (kg) Energy (Kcal) Water Protein 49 6 0 24,000 800 140,000 164,800

Days Available 0 13 0.4 78 91.4

Glycogen 0.2 Fat Total 15 70.2

Metabolism During Fasting

A healthy 70kg adult will use 180 g /d of glucose to support obligate glycolytic cells (neurons, RBCs, PMNs, renal medulla, skeletal m.) Glucagon, Norepi, vasopressin, AngII promote utilization of glycogen stores Glucagon, Epi, and cortisol promote gluconeogenesis Precursors include lactate (sk.m., rbc, pmn), glycerol, and aa (ala, glutamine)

Metabolism of Simple Starvation

Lactate is not sufficient for glucose demands Protein must be degraded (75 g/d) for hepatic gluconeogenesis Proteolysis from decreased insulin and increased cortisol Elevated urinary nitrogen (7 -> 30 g/d)

Metabolism of Prolonged Starvation

Proteolysis is reduced to 20g/d and urinary nitrogen excretion stabilizes to 2-5g/d Organs (myocardium, brain, renal cortex, sk.m) adapt to ketone bodies in 2-24 days Kidneys utilize glutamine and glutamate in gluconeogenesis Adipose stores provide up to 40% calories (approx 160 g FFA and glycerol)

Stimulated by reduced insulin and increased glucagon and catecholamines

Metabolism Following Injury

Magnitude of expenditure is proportional to the severity of injury Changes in

Lipid Absorption

Oxidation of 1g fat = 9 kcal energy Dietary lipids require pancreatic lipase and phospholipase to hydrolyze TG into FFA and monoglycerides within the duodenum After gut absorption, enterocytes resynthesize TG from monoglycerides + fatty acyl-CoA Long chain TG (>12 carbons) enter the circulation as chylomicrons. Shorter FA chains directly enter portal circulation and are transported via albumin Under stress, hepatocytes utilize FFA as fuel Systemically TG and chylomicrons are used from hydrolysis with lipoprotein lipase (suppressed by trauma and sepsis)

Fatty Acid Oxidation

FFA + acyl-CoA = LCT are transported across the mitochondrial inner membrane via the carnitine shuttle Medium-chain TG (MCT) 6-12 carbons long, freely cross the mitochondrial membrane Fatty acyl-CoA undergoes -oxidation to acetylCoA to enter TCA cycle for oxidation to ATP, CO2, and water Excess acetyl-CoA is used for ketogenesis

Carbohydrate Metabolism

Carbohydrates + pancreatic intestinal enzymes yield dimeric units (sucrase, lactase, maltase) Intestinal brush border disaccharidases break them into simple hexose units which are transported into the intestinal mucosa Glucose and galactose are absorbed via a sodium dependent active transport pump Fructose absorption via facilitated diffusion

Carbohydrate Metabolism

1g carbohydrate = 4 kcal energy IV/parenteral nutrition 3.4 kcal/g dextrose In surgical patients dextrose administration is to minimize muscle wasting Glucose can be utilized in a variety of pathways phosphorylation to G6P then glycogenesis or glycogenolysis, pyruvic acid pathway, or pentose shunt

Protein and Amino Acid Metabolism

Average adult protein intake 80-120 g/day

Following injury, glucocorticoids increase urinary nitrogen excretion (>30g/d), peak at 7d, persist 3-7 wks

Nutrition in the Surgical Patient

Nutritional assessment to determine the severity of deficiencies/excess Wt loss, chronic illnesses, dietary habits, quality/quantity of food, social habits, meds Physical exam loss of muscle/adipose tissue, organ dysfunction Biochemical Cr excretion, albumin, prealbumin, total lymphocyte count, transferrin

Surgical Nutrition

Support the requirements for protein synthesis Nonprotein calorie : nitrogen objective ratio = 150:1 A lower rate of 80-100:1 may be beneficial in some critically ill or hypermetabolic patients Basal Energy Expenditure (BEE):
men = 66.47 + 13.75(W) + 5(H) 6.76(A) kcal/d women = 655.1 + 9.56(W) + 1.85(H) 4.68 (A) kcal/d W= wt in kg, H= Ht in cm, A= age in years

Enteral Feeding

Less expensive and risks than parenteral Reduced intestinal atrophy 44% reduction in infections over parenteral in the critically ill Healthy patients without malnutrition undergoing uncomplicated surgery can tolerate 10 d of maintenance IV fluids only before significant protein catabolism begins

Initiation of Enteral Feeding

Immediately after adequate fluid resuscitation (UOP) Not absolute prerequisites: presence of bowel sounds, passage of flatus or stool Gastric residuals of >200ml in 4-6 hrs or abdominal distention requires cessation/lowering the rate

Enteral Formulas

Low-residue isotonic

caloric density 1.0kcal/ml, 1500-1800 ml/day Provide carbs, protein, lytes, water, fat, water sol vitamins, calorie:Nitrogen of 150:1. No fiber bulk = minimum residue Standard for stable patients with an intact GI tract
Soluble and insoluble fiber (soy) Delay GI transit time and reduce diarrhea Not contraindicated in the critically ill

Isotonic with fiber

Enteral Formulas

Immune-Enhancing

Glutamine, argenine, omega-3 FA, nucleotides, beta-carotene. Benefits not consistent in trials Expensive
1.5-2 kcal/ml, higher osmolality (ok for intragastric feeding) for fluid restriction/inability to tolerate larger volumes

Calorie-Dense

High-Protein

Isotonic and nonisotonic available calorie:Nitrogen ratio of 80-120:1

Enteral Formulas

Elemental
Contain predigested nutrients, small peptides Limited complex carbs and fat (long/med chains) Easily absorbed, but limited long term use High osmolality = slow infusion or diluted Expensive

Renal-Failure
Lower fluid volume, K, phos, and Mg Essential aa, high calorie : nitrogen ratio, no vitamins

Enteral Formulas

Pulmonary-Failure
Fat content is increased to 50% of total calories Reduces CO2 production and ventilation burden

Hepatic-Failure
50% of aa are branched chains (Leu, Ile, Val) Potentially reverses encephalopathy Controversial, no clear benefits in trials

Enteral Access

Nasogastric Tube - requires intact mental status and laryngeal reflexes to reduce aspiration

Difficult to place, requires radiographic confirmation If required >30 d, convert to PEG Problems: clogging, kinking, inadvertent removal Impaired swallowing/obstruction, major facial trauma Contraindications: ascites, coagulophathy, gastric varices, gastric neoplasm, lack of suitable location Tubes can be use for 12-24 mos Requires endoscopic transillumination of abdominal wall and passage of catheter into an insufflated stomach Complications in 3% of cases: infection, peritonitis, aspiration/pneumonia, leaks, dislodgement, bowel perforation, enteric fistulas, bleeding

Percutaneous Endoscopic Gastrostomy

Percutaneous Endoscopic Gastrostomy-Jejunostomy

Feeding administered past the pylorus Cannot tolerate gastric feedings/signif aspiration Passes a catheter through an existing PEG past the pylorus into the duodenum Long term malfunction >50% due to retrograde tube migration into the stomach, kinking, clogging

Direct Percutaneous Endoscopic Jejunostomy

Same technique as PEG placement but requires an enteroscope/colonscope to reach the jejunum Less malfunction than PEG-J Kinking/clogging reduced by placing larger caliber catheters

Surgical Gastrostomy and Jejunostomy

With complex abdominal trauma/laparatomy there may be an opportunity for placement Contraindication: distal obstruction, severe intestinal wall edema, radiation enteritis, inflammatory bowel disease, ascites, severe immunodeficiency, bowel ischemia Adverse effects: abdominal/bowel distention, cramps, pneumotosis intestinalis, small bowel necrosis

Parenteral Nutrition

Continuous infusion of hyperosmolar carbs, proteins, fats and other nutrients through a catheter into the SVC Optimal > 100-150 kcal/g nitrogens Higher rates of infection compared to enteral Studies with parenteral nutrition and complete bowel rest results in increased stress hormone and inflammatory responses

Parenteral Nutrition Rationale

Seriously ill patients with malnutrition, sepsis or surgery/trauma when use of the GI tract for feeding is not possible
Short bowel syndrome after massive resection Prolonged paralytic ileus (>7 days) Severe intestinal malabsorption Functional GI disorders esophageal dyskinesia Etc.

Total Parenteral Nutrition

Central parenteral nutrition, aka TPN Requires access to a large diameter vein Dextrose content is high (15-25%)

Peripheral Parenteral Nutrition

Lower osmolality Reduced dextrose (5-10%) Protein (3%) Not appropriate for severe malnutrition due to need for larger volumes of some nutrients Shorter periods, < 2 wks

Parenteral Nutrition

Dextose 15-25% Amino acids 3-5% Vitamins (Vit K is not included) Lipid emulsions to prevent essential FA deficiency (10-15% of calories) Prepared by the pharmacy from commercially available kits If prolonged supplement trace minerals

Zinc (eczematous rash), copper (microcytic anemia), chromium (glucose intolerance)

Parenteral Nutrition

Insulin supplement to insure glucose tolerance IV fluids/electrolytes if high fluid losses Freq. monitor fluid status, vital signs, UOP, electrolytes, BUN, and LFTs. Glucose q6h

Complications

Hyperglycemia pt with impaired glc tolerance or high infusion rate

Tx- volume replacement, correct electrolytes, insulin Avoid by monitoring daily fluid balance, glc, & lytes

Overfeeding results in CO2 retention and respiratory insufficiency Hepatic steatosis Cholestasis and gallstones Hepatic abnormalities serum transaminase, alk phos and bilirubin Intestinal - atrophy from disuse, bacterial overgrowth, reduced lymphoid tissue and IgA production, impaired gut immunity

Special Formulations

Glutamine and Arginine

Glutamine nonessential aa, comprises 66% of free amino acids During stress glu is depleted and shunted as a fuel source to visceral organs and tumors Inconclusive data for benefits of increased supplementation Arginine nonessential aa, promotes net nitrogen retention and protein synthesis in the critically ill/injured. Benefits still under investigation.
Canola or fish oil. Displaces omega-6 FAs, theoretically reducing pro-inflammatory responses ? Increase cell proliferation, DNA synthesis, T Helper cell function

Omega-3 Fatty Acids

Nucleotides

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