Characterizing the Hypermetabolic State

In response to traumatic or thermal injuries, sepsis, or other inflammatory insults, the body’s physiologic response is to stimulate a state of hypermetabolism in an effort to recover and repair tissue damage. The hypermetabolic response to disease (e.g., stressed starvation) is quite different from the metabolic response in healthy animals (adapted starvation) to inadequate nutrition (Table 33-1).^5,6 In both situations, glucose is preferentially metabolized initially to support energy needs, with rapid depletion of hepatic glycogen reserves in the face of inadequate energy intake. Body protein, primarily skeletal muscle, is degraded to release amino acids in providing substrate for hepatic gluconeogenesis. In adapted starvation, energy metabolism ultimately switches from glucose to fatty acids and ketone bodies as fuel resources in all but obligate glucose-utilizing tissues. The basal metabolic rate (BMR) is lowered and the rate of gluconeogenesis is slowed dramatically to conserve body protein. These adaptive responses are specifically directed to minimize body protein wastage.⁸

In contrast to these survival adaptations, the hypermetabolic state is differentially characterized by increased metabolic rate fueled predominately by glucose via continued gluconeogenesis from mobilized amino acids.⁹ Increased protein degradation, coupled with moderately decreased protein synthesis, culminates in extensive skeletal myofibril degradation.^7,10 Increased energy metabolism is sustained in an effort to support tissue repair, immune function, and inflammatory responses at the expense of body protein wastage. Although insulin, glucagon, catecholamines, and glucocorticoids are the primary regulatory hormones controlling metabolic adaptations in both instances, hypermetabolism is uniquely characterized by high concentrations of inflammatory cytokines (e.g., Interleukin (IL)-1, IL-6, tumor necrosis factor alpha [TNF-α]), which promote this metabolic dysfunction of exaggerated proteolysis and increased basal metabolic rate.^7,10 Insulin resistance relative to control over gluconeogenesis is suggested by the lack of responsiveness to insulin or glucose infusions, yet tissue glucose utilization is near maximum.⁸ Fatty acids are readily oxidized, but body fat mobilization is limited as a result of a hyperglycemia-induced state of hyperinsulinemia. Affected animals may effectively retain body fat deposits at the expense of lean body loss. Although the role of increased inflammatory mediators is well recognized as part of the exaggerated hypermetabolic response, the exact mechanism is not understood and most likely is not a consequence of a single mediator.^5,8

Consequences of Hypermetabolism

The primary goal of the hypermetabolic response is to provide substrate in support of the reparative process. The hypermetabolic state provides substrate to increase body temperature in an effort to combat pathogens. For every 1°C increase in body temperature, the BMR is increased by 10% to 15%.⁹ Mobilization of amino acids from body protein provides not only substrate for the gluconeogenic process but also amino acids for hepatic acute phase protein synthesis and for tissue repair. Additional amino acids may be made available to the liver from decreased synthesis of constitutive proteins (e.g., albumin, retinol-binding protein, apoproteins). Laboratory findings of hyperglycemia, hyperlactatemia, hypoalbuminemia, and azotemia are indicators of these metabolic adaptations. Collectively, these responses help support the body’s immune response to the insult, as evidenced by observed leukocytosis and increased mediators of the inflammatory process.

Although the hypermetabolic response is to facilitate recovery, the response is graded along a continuum and may become detrimental if prolonged or exaggerated. Severity of the hypermetabolic state is proportional to the insult and coupled with the stress hormonal milieu as influenced by local and systemic inflammatory mediator and growth factor responses.8,9 With increased energy expenditure, body fuel resources are diminished. Mobilization of body protein results in varying degrees of muscle weakness, fatigue, and atrophy.^7,10 Secondary complications of respiratory distress and thromboembolic risks may manifest following muscle demise. As body protein degradation continues, the state of malnutrition ensures that those tissues dependent on active protein synthesis are most severely affected. As a consequence, wound healing, immune response, and integrity of the intestinal mucosal barrier may be compromised. Failure of the mucosal barrier results in bacterial translocation from the gut lumen to the vascular space, which leads to bacterial septicemia. Multiple organ failure and death are the most common sequelae to septicemia in such compromised patients.⁵

History and Signalment of Problem

The duration and severity of the insult should be considered relative to the initiation of nutritional support, primarily in assessing the length of time the animal has not consumed food and the potential for ongoing nutrient losses. Large open wounds or effusive disease with continuous drainage increase protein losses above and beyond those from hypermetabolism. Anorexia for more than 5 to 7 days in adult animals or 1 to 2 days in neonatal animals would warrant initiation of support. The extent of any preexisting conditions such as cardiac, renal, or hepatic disease that may affect nutritional support decisions must be determined. Animals should be cardiovascularly stable before enteral support is initiated, as the gut may be poorly perfused in lieu of perfusion to other essential organs. Underlying issues of dehydration, acid–base deficits, and electrolyte imbalances need to be evaluated and addressed independent of nutritional support. Historical information should be used to assess potential changes in body weight or body condition score (BCS) over time prior to presentation. The history should also ascertain the current physiologic state of the patient as it would relate to ongoing nutrient requirements.

Determination of Intake Ability

The patient’s ability to consume food determines the appropriate method of nutritional support. If the underlying problem impairs the animal’s ability to chew or swallow, enteral support options may be limited to tube feeding. Camelids are obligate nasal breathers and are highly stressed with orogastric tube placement, thus potentially limiting the extent to which enteral support may be used. Disease conditions of the mandible or the maxilla, fractures, tooth abscesses, inflammatory conditions of the mouth or pharynx, and neurologic conditions may impede the animal’s ability to chew and swallow food. These processes may also impede the camelid’s ability to regurgitate and remasticate C1 contents. Renal or hepatic failure may diminish the animal’s desire to eat.

Estimation of Digestion or Absorption Ability

Some level of clinical assessment of the camelid’s ability to digest consumed food and absorb end products of digestion is another consideration. With camelids being pregastric fermenting species, some assessment of the health of the foregut microbial population should be undertaken. Percutaneous paracentesis of C1 contents has been described and is considered a safe diagnostic procedure in llamas and alpacas, but may not be acceptable in compromised patients.¹² Disease conditions such as C3 ulcers, enteritis, small bowel resection, and colitis, among others, may limit the ability of the animal to process and assimilate enteral nutrients.

Nutritional Status

Methods to assess nutritional status of an individual are detailed elsewhere (see Chapter 12). Readily available objective measures of body composition and energy expenditure are not currently available in veterinary medicine. The simplest measure of nutritional status is a current body weight and some assessment of body weight change over time. Greater than 10% unintentional body weight loss over a period of days to weeks would be of concern in camelids. A study showed that feed-restricted llamas that lost 15% to 20% of body weight over a 1- to 2-week period were more predisposed to hepatic lipidosis.¹³ Lactating females may lose upward of 20% of body weight over the first month of milk production. Neonates losing greater than 5% body weight should be evaluated for nutritional support. The BCS may be used to assess degree of fat reserves as well as body protein, although current systems have not been validated relative to protein changes per unit of BCS. Lower body condition scores (<3 on a 1-to-5 scale) indicate lower subcutaneous body fat deposits but also suggest a loss in skeletal muscle mass as bony processes become more evident. These changes may be seen by using ultrasonographic measures of fat and muscle thickness.

Additional subjective criteria in assessing nutritional status might include a poor-quality hair coat or unexplained fleece loss in camelids. Indications of poor wound healing may also suggest an inadequate nutritional state.

Beyond physical measures of nutritional status, blood analyte concentrations or other blood parameters may be used for secondary assessment of nutritive status. Hypoalbuminemia (<2.0 grams per deciliter [g/dL]) is often considered an indicator of malnutrition, although this often may result from diseases inducing increased blood protein losses. Lymphopenia, although not a specific indicator of nutritional state, is associated with animals in poor nutritional status or under stress. In camelids, other blood analytes such as nonesterified fatty acids (NEFA; >0.8 milliequivalents per liter [mEq/L; >0.8 millimoles per liter [mmol/L]) and β-hydroxybutyrate (BHB; >5 milligrams per deciliter [mg/dL; >0.48 mmol/L]) are indicators of risk for metabolic or energy-related problems.⁴ Other blood analyte indicators of camelid nutritional status have yet to be identified and validated.

Rationale for Use

A cardinal rule of nutrition is “If the gut works, use it.” Providing nutrients via the gastrointestinal tract is more physiologic and may minimize potential complications related to mucosal barrier dysfunction and impaired local immune response. Most data suggest a reduction in mortality in critically ill patients supported by enteral nutrition through a reduction in septic complications leading to death.⁸ Enteral nutrition provides direct nutritional support to enterocytes, which may maintain the physical barrier, as well as having indirect trophic effects.^7,8 Enteral nutrition may also improve mesenteric blood flow and autonomic stimulation, thus improving gut function and activity. Supportive enteral nutrition is critical to maintaining normal functionality to the forestomach fermentation vat.

Appetite Stimulation

A simple approach to improving nutrient intake is to stimulate appetite. Various techniques to increase appetite exist, although these methods are not well understood and documented in camelids.¹⁴ Options include increasing feed palatability or variety, limiting environmental stress factors, pharmacologic stimulation, foregut transfaunation, and provision of a stimulating feeding environment. All of these may have some applicability, with the basic caveat that an intervention should do more good than harm. It should be remembered that correction of dehydration and underlying metabolic abnormalities is the top priority in stimulating intake.

Although many feed characteristics to promote improved palatability are known for companion animals (e.g., moisture, temperature, fat or protein content), extrapolation to camelids may not be appropriate.¹⁴ In our clinical experience, providing a variety of feedstuffs has been the most useful method of stimulating intake. Alfalfa leaves, fresh grass clippings, and blackberry leaves or any other browse material are among the best feeds to help stimulate feed intake.

Environmental factors to consider are freshness of offered feed and availability of water resources. Feed should be available as often as possible, and feeding should not be associated with administration of pharmacologic agents in treating underlying disease. Buddy animals are helpful in some cases, but allowing an animal to eat without competition is often better. A positive environment for feed consumption should be maintained. This may require elevating the feed to facilitate access.

Use of direct fed microbial (DFM) products (“probiotics”) may not be appropriate as compared with transfaunation of rumen juice from another animal. Microbial populations associated with most DFM products include a number of lactobacilli, which are not really desired bacterial species, as they produce lactic acid as a primary fermentation end product. These microbes are more desirable as colonies populating the intestinal tract rather than the forestomach. Rumen juice has the better range of desired microbial populations. Some benefit may be achieved by providing yeast-based products, either live cultures or yeast extracts. Most commercial yeast products are derived from cultures of Saccharomyces cerevisiae. A number of probiotic products may also contain yeast components as well as live bacterial cultures. Yeast products have been shown to generate metabolic derivatives that promote forestomach bacterial growth and subsequently increase dry matter intake and fiber digestibility.15,16 Improving fiber digestibility results in greater volatile fatty acid production in support of energy needs as well as increasing rate of particulate passage allowing for increased intake capability.

Pharmacologic stimulation of appetite is generally of short duration and variable efficacy. Diazepam (0.05 milligrams per kilogram [mg/kg], intravenously [IV]) works very well in some camelids but not at all in others. B-vitamin injections are supposed to stimulate appetite and improve glucose utilization. Analgesic agents may also be effective when pain is inhibiting appetite. Efficacy of other compounds is not well characterized in camelids.