Body Fuels

Human metabolism is organized in such a way, so that fuel consumption occurs in a hierarchical way

when more than one energy source is present, with excess stored for the postprandial or fasting period.

In the postprandial state, the body contains fuel reserves that it can also mobilize in an orderly fashion,

as fasting is prolonged. The same fuel reserves are accessed during stress metabolism, although in a less

orderly fashion (Table 3-1).

Calorically dense fat is by far the largest energy repository, providing 9 kcal/g when mobilized and

oxidized. The ability of the body to store fat is essentially limitless. Protein comprises the next largest

energy store in the human body, yet amino acids when oxidized yield 4 kcal/g. And unlike fat, protein

plays both a structural and functional role in the body, thus, in severe protein loss, major functional

consequences can be expected. In malnutrition, proteolysis frees up amino acids to be used for

gluconeogenesis to produce glucose, which in turn can be used as fuel. Carbohydrate reserves are

minimal and exist in the form of glucose or glycogen in the liver. These can be depleted quickly,

typically within 12 hours, unless replenished through nutrition. Carbohydrates, like protein, also yield

approximately 4 kcal/g when mobilized for energy production (Table 3-2).

Carbohydrates. Carbohydrates are the most commonly used fuel by the human body, providing

frequently over 45% to 60% of daily energy requirements. Each gram of carbohydrate that is

administered enterally yields approximately 4 kcal when broken down, whereas intravenously

administered carbohydrates (such as dextrose-containing solutions) provide slightly less (approximately

3.4 kcal/g).

Table 3-2 Energy Value of Various Energy Sources

The basic unit of carbohydrate metabolism in humans is glucose, and nearly all dietary carbohydrates

are converted to glucose for energy production. Digestion of carbohydrates begins as proximally as the

oral cavity with food ingestion, where salivary amylase breaks down polysaccharides into smaller oligoand disaccharides. This process continues in the duodenum and proximal jejunum with the pancreatic

amylase. Oligosaccharidases that are present in the brush border of the proximal small bowel further

hydrolyze oligosaccharides into di- or monosaccharides, most commonly glucose, to be absorbed by the

gut mucosa. Once glucose reaches the bloodstream, it stimulates secretion of insulin from the endocrine

pancreas (beta cells), which has major anabolic effects and stimulates protein synthesis, inhibits

lipolysis, and upregulates glycogen production. Conversely, during stress, pancreatic glucagon exerts

opposite effects: it promotes breakdown of glycogen, but also fat and protein, to be used as additional

energy sources during a time when energy requirements are maximal. Deficiencies in carbohydrate

digestion are rare in surgical patients, even in patients in whom the pancreatic exocrine function is

significantly decreased. Patients with pre-existing celiac or Whipple disease may, however, have limited

capacity to absorb carbohydrates.

The human central nervous system and circulating blood cells require glucose constantly for their

energy requirements. In periods of extended fasting, after the liver has used up its stores of glycogen,

the human body breaks down protein and uses the resulting amino acids to generate glucose, and even

converts fat into ketones that can partly substitute glucose as an energy source. When glucose is

reinstated through nutrition, these metabolic adaptations are completely reversed. During stress,

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gluconeogenesis and glycogen breakdown is accelerated and ketone production minimized, leading to

an abundance of glucose for use as the human body mounts an inflammatory response.

Lipids. Lipids are the second most commonly used fuel for energy by the human body, accounting for

35% to 45% of daily caloric intake. Each gram of fat yields approximately 9 kcal of energy when

oxidized. When lipids enter the proximal small bowel, cholecystokinin and secretin are released, which

make the gallbladder contract and release bile into the duodenum. Bile salts contained in bile are

necessary for lipid absorption, especially the long-chain fatty acids that are found in a typical western

diet, which occurs mostly in the distal ileum. Surgical resection of the distal ileum may lead to depletion

of the bile salt pool and fat malabsorption.

Lipids are most commonly classified by the length of their contained hydrocarbon chains. Short-chain

fatty acids typically refer to lipids containing 2 to 5 carbon length chains and are a product of dietary

fiber fermentation in the colon by the intestinal flora. They are absorbed by and are the preferred fuel

for the colonocytes. Medium-chain fatty acids (6 to 9 carbon length chains) are also not typically found

in the human diet, but are commonly used in numerous enteral nutrition formulas, as they are easier to

digest, compared to longer chain triglycerides. They are water soluble, and hence require no

emulsification or micelle formation for transport. Lipase is not required. The medium-chain triglycerides

are absorbed directly into the portal circulation. Unlike the short- and medium-chain fatty acids which

can be produced from other dietary substrates, two long-chain fatty acids (>9 carbon length chains),

linoleic and linolenic acids, are essential for human nutrition. These are not water soluble and require

bile salts for emulsification as stated above, lipase for digestion, and micelle/chylomicron formation for

transport. They gain access to the bloodstream via the lymphatic system (thoracic duct). Insufficient

intake of these essential fats can lead to fatty acid deficiency, which can be prevented with provision of

at least 3% to 4% of the daily calories as linoleic and linolenic acids. These two fatty acids are also a

precursor of eicosanoids, significant mediators of the inflammatory response. On a cellular level,

lipoprotein lipase is necessary for intake, and carnitine for transport from the cytosol into the

mitochondria for oxidation. Long-chain triglycerides are the main form of energy storage in the human

body, given the numerous high-energy bonds they contain.

Protein. Protein is different from carbohydrate and lipids in that it contains nitrogen that neither fatty

acids nor glucose do. It is also a key structural component, and there are no inactive protein stores.

Essentially all proteins are either functional or structural in the human body.

Proteins are polypeptides, containing numerous amino acids as their building blocks, and yield 4

kcal/g when used for energy production. Dietary protein is broken down into amino acids and smaller

peptides by gastric pepsin and pancreatic proteases, the latter activated by enterokinase in the

duodenum. These amino acids and oligopeptides get absorbed mostly in the proximal gastrointestinal

tract and travel to the liver, where they are recycled to synthesize new protein. In a healthy, 70-kg

weighing adult male over 300 g of protein are recycled daily. The branched-chain amino acids (BCAAs;

leucine, isoleucine, and valine) are transported to muscle unaltered, while other amino acids are

distributed to the intra- and extracellular pool for protein synthesis as needed. Excess amino acids are

usually converted to glycogen or free fatty acids.

In addition to the dietary protein, intracellular proteins are continuously recycled, and the resulting

free nitrogen is excreted, mostly through urine. Most of the urine nitrogen is in the form of urea (85%),

with smaller amounts excreted as creatinine and ammonia. Urinary nitrogen decreases significantly with

protein-free diets (decreased intake), but increases during stress (greater turnover).

Amino acid metabolism generates ammonia, a highly toxic compound, which is converted into urea

(nontoxic) in the liver. Glutamine and alanine serve as ammonia-transporting vehicles in a nontoxic

form from the metabolically active peripheral tissues to the viscera. There, ammonia is resynthesized

and either excreted (by the kidneys, where it also acts as a buffering system) or detoxified to urea

(liver). Diseases that affect the functional capacity of either the kidneys or the liver can lead to

significant ammonia build up in the body, with potentially toxic consequences to the central nervous

system.

Other Nutrients

To maintain health, in addition to energy, numerous other nutrients are required for the numerous

metabolic functions of the human body. These include nucleotides, vitamins, and trace elements. The

former are increasingly identified as important for the nutrition of the critically ill patient, whereas

vitamins and trace elements are important for numerous anabolic functions.

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Nucleotides. Nucleic acids are the building blocks for DNA and RNA, and are not typically considered

essential for a balanced nutrition in healthy adults. However, dietary requirements become significant

during severe stress and critical illness, as nucleic acids are necessary for rapidly proliferating cells, such

as the cells participating in the immune function. Diets augmented with RNA or the nucleotide uracil

have been shown to restore delayed hypersensitivity and improve the lymphoproliferative response. As

such, they have been included in enteral nutrition formulas, where they may aid recovery from severe

infections.13

Vitamins. Vitamins A, D, E, and K are fat soluble and are absorbed in the small bowel in association

with long-chain fatty acids. From there, they are transported to the liver (vitamins A and K) or the skin

and subcutaneous tissue (vitamins D and E) for storage. Fat-soluble vitamins are required for normal

immune function and play a significant role in wound healing. Daily vitamin A intake in patients on

chronic corticosteroid regimens may counteract most of steroid-mediated adverse effects of wound

healing.

Unlike vitamins A, D, E, and K, vitamins B1, B2, B6, and B12, along with vitamin C, niacin, folate,

biotin, and pantothenic acid are water soluble and are absorbed in the proximal small bowel. From

there, they are transferred to the liver with the portal circulation for use or storage. Water-soluble

vitamins are required for normal amino and nucleic acid metabolism.

Electrolytes and Trace Elements. Electrolytes are important components of both the intra- and

extracellular compartment, where they play a major role in maintaining electrical and osmotic balance

across the body’s plasma membranes. Such electrolytes include sodium (Na+), potassium (K+), calcium

(Ca2+), magnesium (Mg2+), chloride (Cl−), and are cations (with a positive charge) or anions (with a

negative charge), due to uneven distribution of electrons. Sodium is the main extracellular electrolyte

and is important in maintaining volume homeostasis and blood pressure control. Conversely, potassium

is one of the key intracellular cations. The role of electrolytes is diverse, and includes functions as

varied as the conduction of electric signals, cotransport of larger molecules against their concentration

gradient, muscular contraction, and participation in numerous essential biochemical reactions.

Trace elements play an important role in numerous metabolic, immunologic, and healing functions

and eight minerals have been identified as “essential.” These include iron, iodine, zinc, chromium,

copper, selenium, manganese, and molybdenum.

Iron is an integral component of the heme core in hemoglobin and of the mitochondrial cytochrome

complex. Subtle impairments in central nervous, musculoskeletal, and immune system function can be

identified in patients with iron deficiency, before microcytic anemia becomes clinically evident.

Impaired cerebral, muscular, and immunologic function can occur in patients with iron deficiency before

anemia becomes clinically evident. Particular attention has to be paid to pregnant and lactating females,

in whom iron requirements are even greater than the rest of the population.

Iodine is a key component of the thyroidal hormonal system. Deficiencies are rare in the western

world, due to widespread use of iodinated salt. However, chronically malnourished patients can develop

significant iodine deficiency, which can typically manifest clinically as diffuse goiter and

hypothyroidism.

Zinc deficiency can manifest with skin discoloration and perioral rash, neuritis, hair loss, and

alterations in taste and smell. Chromium deficiency presents as impaired glucose tolerance during

prolonged fasting and is fairly common with total parenteral nutrition (TPN). Copper deficiency

presents with microcytic anemia, typically unresponsive to iron, abnormal skin keratinization, and, in

its most severe cases, pancytopenia. Selenium deficiency, which can similarly be identified in cases of

prolonged TPN administration, manifests as neuromuscular dysfunction or cardiac conduction defects,

which in the most severe cases can lead to heart failure. Manganese deficiency can be identified as the

underlying cause in a syndrome presenting as unintentional weight loss, hair color changes, and

hypolipidemia. Molybdenum deficiency is associated with hypomethioninemia and hypouricemia,

resulting in nausea and vomiting, tachycardia, and nonfocal central nervous system dysfunction (Table

3-3).

Nutritional Assessment

Metabolism is altered to varying degrees by stress, namely surgical injury, critical illness, infection, and

physical trauma. In most cases, these alterations are short lived and reversible in a previously wellnourished individual, even if fasting is superimposed during acute illness. However, pre-existing

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