Pamela Hughes, Jon P. Bradrick and Charles J. Yowler

Outline

Fasting- and Starvation-Induced Malnutrition Physiology

A healthy 75-kg man normally stores 200 to 300 g of carbohydrate, equal to 800 to 1200 kcal (4 kcal/g), mostly as glycogen.³ Fat is normally 15% to 30% (11 to 22 kg) and protein 14% to 20% (10 to 15 kg) of body weight. The average total caloric reservoir is therefore approximately 200,000 kcal, of which 75% is fat. In the complete absence of nutritional intake, an otherwise healthy person could catabolize 1 to 2 g/kg of protein and 2 to 3 g/kg of fat/day. Theoretically, this caloric reserve could sustain life for 3 to 5 months. Realistically, death would occur after burning about 140,000 kcal (75% body fat and 50% body protein).⁴

Starvation involves a cascade of substitution of energy substrates as the body attempts to conserve energy resources and cellular functions. With the onset of starvation, glycogenolysis provides most of the necessary blood glucose. The available glycogen stores are rapidly depleted, and amino acids become the prime source of carbon for hepatic gluconeogenesis. The amino acid sources are muscle, connective tissue, and visceral proteins. As starvation continues, the rate of gluconeogenesis diminishes, coincident with a decrease in metabolic rate and increase in ketone use as fuel by the central nervous system. The early loss of body mass is slowed and accompanied by a decrease in urinary nitrogen excretion. In a healthy patient, nitrogen intake equals urinary excretion, about 10 to 30 g/day. In fasting starvation, urinary nitrogen excretion falls to 3 to 4 g/day, reflecting protein and therefore amino acid conservation.⁴ Because hepatic and GI function are more acutely affected by decreased protein intake, compromised function of both will rapidly develop. One kg of muscle equals roughly 800 kcal, and 1 kg fat equals 7000 kcal, resulting in greater weight loss when muscle is used as an energy source. This is the basis for the correlation of anthropometric measurements with malnutrition (see later).⁵

The brain normally uses glucose as its sole energy source. During starvation, the central nervous system (CNS) converts to the use of fat. Fatty acids cannot cross the blood-brain barrier for use as fuel, but ketones and ketoacids provided by hepatic metabolism of fatty acids can. As starvation continues, the glucose requirement of the CNS falls about 70% and the requirement for gluconeogenesis by the body falls about 50%. This results in significant sparing of lean body mass.

Trauma-, Stress-, and Sepsis-Induced Malnutrition Physiology

Malnutrition can be thought of as a spectrum. One end is the conservative rationing of body energy resources in fasting starvation. The other end is hypermetabolism induced by stress, such as trauma or sepsis. This hypercatabolic state is a neuroendocrine-mediated response to dead tissue, injured tissue, severe perfusion deficits, and invading microorganisms.⁶ The components of the response are the CNS, macroendocrine hormones, and microendocrine cytokines.⁷ The macroendocrine mediators are the anti-insulin, counterregulatory stress hormones—cortisol, glucagon, and catecholamines. Together, their actions are considered synergistic in this response.⁸ Especially in large wounds, such as cutaneous burns, the microendocrine response is mediated on a cellular level by interleukin-1, tumor necrosis factor, and interleukin-6.⁹ However, the total degree and severity of the hypermetabolic response cannot be predicted based only on the severity of the injury.

The manifestations of the neuroendocrine response are increased basal metabolic rate, increased core temperature, increased oxygen consumption, hyperdynamic circulation, loss of lean body mass, reduced insulin release, marked lipolysis with reduced hepatic ketogenesis, increased gluconeogenesis unresponsive to glucose administration, increase in lactate and pyruvate production and release, increased amino acid oxidation and efflux from peripheral stores, increased hepatic protein synthesis, and ureagenesis.7,10 These hypermetabolic responses can be duplicated in normal patients who are given levels of epinephrine, cortisol, and glucagon in concentrations seen in stressed patients.¹¹ After activation, the hypermetabolic response peaks at 48 to 72 hours. It then subsides over another 3 to 4 days. Loss of important vitamins, trace elements, and minerals occurs very rapidly. Malnutrition will result within days. Complications such as infection will prevent the hypermetabolic response from subsiding. A vicious circle may develop because hypermetabolic patients have increased susceptibility to infection and poor wound healing. The response will once again subside if these complications can be controlled. With repeated episodes or persistent hypermetabolic state, organ failure will result.⁷ End-stage organ failure is manifested by liver failure, triglyceride intolerance, rapid rise in lactate levels, reduced amino acid clearance, reduced hepatic protein synthesis, and marked increase in catabolism, with ureagenesis with prerenal azotemia. Once this occurs, it is unresponsive to any nutritional supportive efforts.¹² Table 3-1 is a summary of fasting starvation compared with hypermetabolic catabolism.

Substrate Depletion and Requirements

Given the spectrum from fasting starvation to hypermetabolic catabolism, the clinician must understand the difference between nutritional and metabolic support, as described by Cerra.⁷ In both, the patient’s energy and substrate requirements must be met. The proper nutritional support, however, is dependent on how the patient’s neuroendocrine axis was activated. In fasting starvation, the hormonal response is activated not by starvation, but by the reintroduction of nutritional support. In stress the hormonal response is activated by the stress insult and subsequent nutritional support. Nutritional support therapy of the stressed hypermetabolic patient is more appropriately termed metabolic support because the substrate doses are adjusted to accommodate the metabolic response to injury. Table 3-2^13,14 compares substrate use in starvation to hypermetabolism.

Assessment Tools for Diagnosis of Nutritional Failure