The broad brush-stroke fundamentals of intermediary metabolism have been known for years, however,

knowledge on the details expands at an ever-increasing rate. A working understanding of the

fundamental biochemical reactions by which substrates are metabolized is important for all surgical

disciplines. Advanced knowledge of the genetics, cellular biology, bioenergetics, and molecular biology

is being exploited to support and perhaps enhance general and specialized cellular function, combat

disease, and improve health.

References

1. Lodish H, Berk A, Kaiser CA, et al., eds. Molecular Cell Biology. 7th ed. New York, NY: WH Freeman;

2013:699–704.

2. The ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocolbased care for early septic shock. N Engl J Med 2014;370:1683–1693.

3. Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as

goals of early sepsis therapy. JAMA 2010;303(8):739–746.

4. Whittaker SA, Fuchs BD, Gaieski DF, et al. Epidemiology and outcomes in patient with severe sepsis

admitted to the hospital wards. J Crit Care 2015;30(1):78–84. Available from:

http://dx.doi.org/10.1016/j.jcrc.2014.07.012. Accessed May 27, 2016.

5. Berg JM, Tymoczko JL, Stryer L, et al., eds. Biochemistry. 7th ed. New York, NY: WH Freeman;

2012:601–605.

6. Botham KM, Mayes PA. Lipid transport and storage. In: Murray RK, Bender DA, Botham KM, et al.,

eds. Harper’s Illustrated Biochemistry. 29th ed. New York, NY: McGraw-Hill; 2012:237–249.

7. Bauer RC, Stylianou IM, Rader DJ. Functional validation of new pathways in lipoprotein

metabolism identified by human genetics. Curr Opin Lipidol 2011;22:123–128.

8. Turner N, Cooney GJ, Kraegen EW, et al. Fatty acid metabolism, energy expenditure and insulin

resistance in muscle. J Endo 2014;220:T61–T79.

9. Römisch K. Endoplasmic reticulum-associated degradation. Annu Rev Cell Dev Biol 2005;21:435–456.

10. Brosnan JT. Interorgan amino acid transport and its regulation. J Nutr 2003;133(6 suppl 1):2068S–

2072S.

11. Berg JM, Tymoczko JL, Stryer L, et al., eds. Biochemistry. 7th ed. New York, NY: WH Freeman;

2012:711–722.

12. Ah Mew N, Lanpher BC, Gropman A, et al. Urea Cycle Disorders Overview. In: Pagon RA, Adam

MP, Ardinger HH, et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington;

2003:1993–2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1217/. Accessed May

27, 2016.

13. Lodish H, Berk A, Kaiser CA, et al., eds. Molecular Cell Biology. 7th ed. New York, NY: WH Freeman;

2013:517–552.

14. Koliaki C, Roden M. Hepatic energy metabolism in human diabetes mellitus, obesity, and nonalcoholic fatty liver disease. Mol Cell Endo 2013;379:35–42.

15. Chapter 12: cellular energetics. In: Lodish H, Berk A, Kaiser CA, et al., eds. Molecular Cell Biology.

7th ed. New York, NY: WH Freeman; 2013:531–532.

16. Rosen ED, Spiegelman BM. What we talk about when we talk about fat. Cell 2014;156:20–44.

17. Riddick DS. Drug biotransformation. In: Kalant H, Grant DM, Mitchell J, eds. Principles of Medical

Pharmacology. 7th ed. Toronto: Saunders-Elsevier; 2007.

18. Bonkovsky HL, Guo JT, Hou W, et al. Porphyrin and heme metabolism and the porphyrias. Compr

Physiol 2013;3(1):365–401.

19. Winter WE, Bazydlo LA, Harris NS. The molecular biology of human iron metabolism. Lab Med

2014;45(2):92–102.

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Chapter 3

Surgical Nutrition and Metabolism

George Kasotakis

Key Points

1 Starvation and systemic inflammatory response result in erosion of the fat-free mass and body

weight (malnutrition) and are indicators for nutrition support if present.

2 Inflammation increases energy utilization and alters the metabolism of glucose, protein, fat, and

trace minerals.

3 Hypermetabolism is seen in numerous disease states, and not merely in trauma and sepsis.

4 Numerous methods exist to aid assessment of patients’ nutritional status, each with its own

advantages and disadvantages.

5 A strong relation between protein depletion and postoperative complications has been demonstrated

in nonseptic, nonimmunocompromised patients undergoing elective major gastrointestinal surgery.

6 The main goal of perioperative or posttraumatic nutritional support is repletion or maintenance of

protein, energy stores, and other nutrients to allow rapid and full recovery from illness.

7 Whenever providing nutritional support, supply caloric intake in the form of carbohydrate and fat in

a 2:1 ratio, if no contraindications exist.

8 Enteral nutritional support is always preferable than parenteral nutrition, in the presence of a

functioning gastrointestinal tract.

9 The maintenance of an intact brush border and intercellular tight junctions prevents the movement

of toxic substances into the intestinal circulation and minimizes bacterial translocation. These

functions may be affected in critical illness. Enteral nutrition helps restore them.

10 Allow hypocaloric enteral feedings in the acute phase of critical illness for up to 5 to 7 days in

previously well-nourished patients. Start as early as feasible.

11 Routine glutamine supplementation is not supported during critical illness.

12 Supply micronutrients to prevent refeeding syndrome, and monitor electrolytes, liver function tests,

and triglyceride levels as needed.

13 The adequacy of nutritional support should be reassessed frequently and adjustments made as

needed until full convalescence.

INTRODUCTION

Patients undergoing gastrointestinal procedures with evidence of malnutrition at baseline are more

likely to suffer postoperative morbidity, mortality, and require longer hospital stays compared to their

well-nourished counterparts.1,2 The problem is greater than most realize, with up to 14% of patients

scheduled for elective gastrointestinal tract procedures found to be malnourished and up to 40% of

those with gastrointestinal disease found to be at risk for malnutrition.3 It has been shown that poor

nutritional status can detrimentally affect postoperative outcomes,4 and in a consensus review of

Enhanced Recovery After Surgery, it was recommended that patients receive carbohydrate loading 24

hours preoperatively and nutritional supplements, from the day of surgery, until oral intake is

achieved.5

In addition to patients undergoing elective surgery, severe injury and critical illness are associated

with a hypermetabolic state that can increase energy expenditure dramatically and complicate the

resuscitation and recovery of the critically ill or severe injury victim. Over the last few years,

aggressive nutritional support has been underlined as an integral part of the caring of the critically ill

surgical patient, and the Society for Critical Care Medicine (SCCM) and the American Society for

Parenteral and Enteral Nutrition (ASPEN) have made recommendations toward providing early,

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aggressive nutritional support that enables patients to preserve their immune function, maintain lean

body mass, and minimize metabolic complications.6,7 This chapter addresses the areas of nutritional

assessment and management of the surgical patient, reviewing key metabolic principles and providing

an overview of pertinent literature.

BASIC METABOLIC PRINCIPLES

Body Composition

Total body mass is composed of aqueous and nonaqueous components, with the former constituting

approximately 55% to 60% of total body mass (total body water, TBW). Mineralized bone and adipose

tissue make up the majority of the nonaqueous component. The relationship between total body mass

and TBW is relatively constant for an individual and typically reflects the amount of body fat. Solid

organs and muscle contain a higher proportion of water than bone and fat, therefore young lean males

have a higher proportion of their total body mass as water, compared to obese or elderly individuals.

Obesity, older age, and female gender shift the body composition to a greater fat mass (Fig. 3-1).8

The aqueous portion is divided into three functional fluid compartments: plasma (5% of body

weight), interstitial or extracellular fluid (ECF; 15% of body weight), and intracellular fluid (ICF; 40%

of body weight) (Fig. 3-2). In a typical 70-kg male, there are approximately 3.5 L of plasma, 10.5 L of

interstitial fluid, and 28 L of intracellular volume, while the remainder 28 kg represent the nonaqueous

portion. Of the above, the body cell mass constitutes the metabolic engine of the body, while the

extracellular component forms the supporting “scaffolding” for the body cell mass.

Figure 3-1. Body composition as a function of gender and age. (Data from Cohn SH, Vaartsky D, Yasumura S, et al. Compartmental

body composition based on total-body nitrogen, potassium, and calcium. Am J Physiol 1980; 239:E524–E530.)

In clinical practice, body composition is inferred indirectly using the body mass index (BMI; kg/m2),

which reflects the fatty proportion of the total body weight. According to the Centers for Disease

Control and Prevention, a BMI between 25 and 29.9 kg/m2 is indicative of being overweight, whereas

an individual with a BMI of ≥30 kg/m2 is considered obese.

Body composition may change acutely after trauma or major surgery.9 These changes are

characterized by a rapid loss of lean body mass and expansion of the ECF compartment, the latter

manifesting clinically as edema. The underlying changes in body cell mass and fat mass are difficult to

recognize until much later in the process, when they manifest as temporal or extremity wasting. Tools

to assess changes in body composition during critical illness have been described (arm circumference

and tissue bioelectrical impedance), but their use and utility in daily clinical practice are limited.10–12

Energy and Substrate Metabolism

Energy Production and Measurement

The human body functions much like an engine, in that it uses oxygen to burn fuel (carbohydrate, fat,

and protein) and generate energy, excreting the byproducts of this combustion (carbon dioxide, water,

urea, and heat) to the environment (Fig. 3-3). This energy, which is necessary for numerous functions of

the human body, both on micro- (molecular synthesis and transport) and macroscopic (breathing and

mobility) levels, is derived from the energy present in the chemical bonds of the nutrients consumed.

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When no nutrition is provided, such as during periods of starvation or immediately after surgery or

trauma, the body oxidizes stored fuel to generate energy.

Figure 3-2. Aqueous and nonaqueous body composition.

The energy production process is relatively inefficient, as approximately half of the nutrientcontaining energy is eventually converted to heat, instead of all of it being utilized for work. Some of

this heat is used to help maintain body temperature (via meticulously regulated hypothalamic

mechanisms), while the remainder is released to the environment – mostly through the skin. During

illness, or following surgery or trauma, the central temperature regulating mechanisms become reset,

leading to the development of fever, usually an appropriate response to a physiologic stressor. This

increase in body temperature typically intensifies the rate of enzymatic-facilitated chemical reactions

that are essential to the inflammatory response.

All energy produced by the human body comes from oxidation of fuel via a series of

decarboxylation/dehydrogenation reactions. The fuel undergoing oxidation is derived from food or

mobilization of fuel stores. The energy released by these reactions is captured in adenosine triphosphate

(ATP), the human body’s energy “coin,” via a series of redox reactions. In the final step of energy

production from carbohydrates or fat, hydrogen is combined with oxygen to form water. The oxygen

required and the carbon dioxide produced in this process are transported by the circulatory system and

exchanged with the environment by the lungs. Protein oxidation is a special case, in which nitrogen is a

byproduct, in addition to carbon dioxide and water. This nitrogen is removed by the kidneys, after

conversion to urea by the liver.

Energy is measured in joules or calories. The joule is the SI unit of energy and is defined as the

energy required to exert a force of 1 N for a distance of 1 m (unit of measure is kg/m2/s

2). In the

United States, energy is most commonly measured in g-calories (gram-calories) or kg-calories (kilocalories or kcal). A g-calorie is the amount of heat required to raise the temperature of 1 g of water

from 14.5°C to 15.5°C at the pressure of one standard atmosphere, whereas the kg-calorie is the amount

of heat needed to increase the temperature of 1 kg of water under the same circumstances. Joules and

g-calories are very small units of energy (1 J is expended by a resting person every hundredth of a

second), therefore megajoules (MJ) and kilocalories are far more commonly used to describe energy

produced from human nutrition. A megajoule is equivalent to 106 J, while a kilocalorie is equivalent to

103 calories. One megajoule corresponds to 239 kcal.

Figure 3-3. Fuel utilization in human metabolism.

CLASSIFICATION

Table 3-1 Fuel Reserves of a Healthy, 70-kg Adult Male

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