More On The Clinical And Metabolic Foundation Of Entry Level Clinical Nutrition™: The Acute Phase Response
In part IV of this series I began a review of the excellent book chapter by Martindale et al (1) that describes the many metabolic changes that occur with sickness regardless of whether the sickness involves a crises care burn patient or a chronically ill chronic fatigue syndrome patient. I would now like to continue this review by focusing on the section entitled “The mediators of the response.” Kushner and Rzewnicki (2) examined these mediators almost solely from an inflammatory perspective, focusing on cytokines and acute phase proteins. As you will see, while Martindale et al (1) certainly address these issues, they also point out the mediators of which we are most familiar, stress hormones.
The impact of stress hormones on nutrient metabolism
In the section entitled “The counter-regulatory hormones,” the authors state:
“These are the ‘fight or flight’ hormones such as glucagons, catecholamines, and the glucocorticoids. They are found to be markedly elevated during surgical stress, trauma, sepsis, and critical illness. The net result of their elevation is increased protein mobilization, hyperglycemia, insulin resistance, and increased lipolysis. Glucagon stimulates gluconeogenesis, cortisol increases net protein catabolism, and the catecholamines result in glucose intolerance.”
Of course, issues of glucose/insulin imbalances and protein catabolism are two of the most important metabolic factors of Entry level clinical Nutrition™ that we must optimize to gain meaningful results in chronically ill patients. While Kushner and Rzewnicki (2) tended to look at these factors from the very important but still under appreciated perspective of chronic inflammation, suboptimal levels of stress hormones, as we have been learning for years, are, as stated by Martindale et al (1), just as important.
More on inflammatory mediators and their impact on metabolic and nutritional status
As was noted by Kushner and Rzewnicki (2), cytokines are the primary inflammatory modulators of metabolism. According to Martindale et al (1) tumor necrosis factor alphas (TNFα) is one of the most important in terms of inducing a catabolic state:
“TNF induces a net catabolic state by (1) mediating increased catabolism at the level of the specific tissues, (2) causing anorexia, and (3) activating the hypothalamic-pituitary-adrenal axis. The effects of TNF are dose related and can potentially result in catastrophic tissue injury and lethal shock.”
Of course, TNFα takes on even more clinical significance for our day to day dealings with patients than may be suggested in the above quote when it is realized that it is the primary driver of the fever seen in such conditions as influenza (3). In turn, as suggested in the above quote, TNFα is a primary cause of the highly publicized negative sequalae that often accompanies influenza, particularly swine flu. Another major cytokine driving catabolic physiology is interleukin 1 (IL-1), as noted by the authors:
“IL-1 is a key mediator of the acute phase response. In low concentrations, IL-1 is beneficial to the host and stimulates defense mechanisms. However, during critical illness and surgical stress, it has
been reported to be associated with the development of fever, hypotension, inflammation, and accelerated protein breakdown.”
Before continuing, please note again in the above quote “In low concentrations, IL-1 is beneficial…” As I have been suggesting repeatedly, the acute/chronic phase response and all its inflammatory drivers are actually quite important to the optimization of human existence. Too much occurring for too long is usually when bad things happen.
Next, Martindale et al (1) discuss IL-6 and all of the acute phase reactants I have mentioned previously:
“IL-6 is associated with stimulation of the release of hepatic acute phase reactants. C-reactive protein, fibronectin, antitrypsin, ceruloplasmin, and 1-acid glycoprotein are considered acute phase reactants. Trace elements including zinc, selenium, and iron decrease while copper increases in response to IL-6.”
What is the net result of all of the above I have just described? While what I am about to present is fundamentally the same as what I presented in the review of the Kushner and Rzewnicki (2) chapter, I feel it is so important that it bears repeating:
“The net result is the mobilization of endogenous substrates for tissue repair, energy, and support of the immune system.”
What does this mean in more simple, clinically relevant terms? First, it is quite possible that the supplemental protein you are dosing with the intention of building muscle or detoxification enzymes may actually go to the production of more inflammatory mediators such as C-reactive protein. Second, your efforts to rebuild key tissues such as muscle or gut lining may be sabotaged by the fact that the body may be tearing down these tissues faster than you can build them up so as to free constituents for the production of energy and/or the repair of other tissues deemed more necessary from a stress physiology standpoint. In turn, a basic tenet of Entry Level Clinical Nutrition™ is to institute efforts to reduce inflammation either concurrently or before any efforts are made to rebuild any protein based structures such as muscle, gut lining, or detoxification enzymes.
Specific alterations of nutrient metabolism during the stress response
Next I would like to review the portion of the text by Martindale et al (1) that probably has the most clinical relevance to nutritional practitioners, the direct impact of stress on nutrient metabolism. In beginning their discussion of the subject, the authors first point out total body energy stores:
“When reviewing nutrient metabolism, one must consider total body energy stores. Adipose tissue triglyceride storage in the average 70 kg male consists of approximately 140,000 calories. Muscle contains approximately 24,000 calories of protein, 2,000 calories of glycogen and approximately 3,000 calories from triglyceride. The liver contains 300 calories of glucose in the form of glycogen and 500 calories available from triglyceride.”
Before continuing, please note again how little energy is stored in the form of glycogen. In turn, as I hope you can see, with prolonged stress, the body will need to turn to other sources of glucose which, more often than not, will be protein via gluconeogenesis. How long will it take before protein starts to be used as an energy source? First, consider the situation where the patient is not ingesting ideal amounts of protein or what the authors call “unstressed starvation.” Martindale et al (1) state:
“During unstressed starvation, the body mainly relies on mobilization of endogenous adipose stores for its calorie requirements. Adipose utilization follows a brief period in which glycogen stores are mobilized. In situations of unstressed starvation, most glycogen stores are depleted within 18 to 24 hours. During the initial 24 to 48 hours of unstressed starvation, the basic energy needs are supplied by glycogen and protein with some contribution from fat stores.”
Before continuing, please consider three thoughts. First, the quote above refers to an unstressed situation, which is vastly different from most of your patients. Second, even though the vast majority of your patients are not experiencing actual starvation, I would suspect that many, if not most, are experiencing some form of metabolic intracellular starvation due to the presence of insulin resistance, which, as most of you know, is almost universal in chronically ill, chronically stressed patients and greatly retards intracellular uptake of many key nutrients. Third, and possibly most important, the metabolic phenomena suggested in the above quote have not been occurring in your chronically ill patients for hours but months and years.
Next, Martindale et al (1), in relation to unstressed starvation, make an incredibly important point about gluconeogenesis in terms of the source of protein that is being converted to glucose:
“…it is important to realize that there is very little protein storage per se, and that any protein utilized for gluconeogenesis and acute phase protein synthesis should be considered as loss of functional myofibrillar protein.”
Thus, if your patient is has been ingesting suboptimal amounts of protein for any length of time, it is very likely that your patient is experiencing gluconeogenesis to a certain extent. In turn, with any appreciable level of gluconeogenesis, loss of functional protein, most often from muscle or gut lining, will be an inevitable result. Because of this, as you might expect, Entry Level Clinical Nutrition™ makes rebuilding of muscle and gut lining a very high priority early on in patient treatment.
How much protein loss needs to occur before organ function is significantly impaired? The authors state:
“…most physiologic functions become impaired when 20% of body protein is depleted. Wasting has been shown to impair most organ systems, including respiratory, cardiac, and the immune system.”
How can we determine when patients reach this level of loss of body protein? I would suggest that, while it is not a perfect measurement, we can evaluate body composition using bioelectric impedance technology. As most of you know, the ideal female has about 72 – 78% lean body mass and the ideal male has about 82 – 88% lean body mass. I would suggest that reductions of these numbers by 15 – 20%, which, as you also know, is often seen in obese individuals, would lead to a very strong suspicion that body protein is being lost with attendant loss of function in many, if not most, key organ systems.
Next, Martindale et al (1) discuss the impact of stressful situations on protein metabolism, first reviewing what was mentioned above concerning the mediators of the total body response to these stressors:
“As opposed to unstressed starvation, hypermetabolism associated with major catabolic illness, surgery, or trauma results in significant alterations in nutrient homeostasis. As mentioned earlier, systemic hormonal responses to the metabolic insult results in increased ACTH, epinephrine, glucagons, and cortisol production, as well as a host of proinflammatory cytokines such as IL-1, IL-2, IL-6, and TNF in addition to other systemic mediators. These factors, as well as localized tissue ischemia and acidosis, will amplify the catabolic response.”
Before continuing, please note again the additive effect of tissue acidosis, a foundational issue in Entry Level Clinical Nutrition™.
The authors then continue their discussion of what happens in terms of the impact of stressors on nutrient metabolism:
“Similar to unstressed starvation, glycogen stores are exhausted within 12 to 24 hours. In contrast to unstressed starvation, hypermetabolism and gluconeogenesis continue at an accelerated rate. Gluconeogenesis yields the majority of the carbohydrate source to the tissues that require glucose. Muscle protein, in addition to providing the carbon skeleton for gluconeogenesis, serves as a substrate for acute phase protein synthesis by providing the necessary amino acids. As a result of the catabolic insult, the liver reprioritizes its protein synthesis from the production of visceral protein to acute phase proteins. Glutamine and alanine are released from the muscle, delivering glutamine to the gastrointestinal tract and kidney and alanine to the liver for gluconeogenesis.”
Before continuing, I would like to emphasize two key points from this incredibly important and informative quote:
- If acute phase protein synthesis is rising, as suggested by elevated C-reactive protein (CRP), the protein that was used to make CRP came from muscle.
- As I have noted previously, when metabolic stress occurs, the liver reduces the production of proteins used by key organ systems and increases production of inflammatory proteins. Therefore, when you see an elevated CRP, growth and repair of key organ systems is decreasing.
Next Martindale et al (1) discuss the impact of metabolic stressors on glucose metabolism:
“Hyperglycemia is a common occurrence during the hypermetabolic state and is thought to result from an accelerated gluconeogenesis and the relative peripheral insulin resistance. This hyperglycemia associated with hypermetabolic stress is seen despite the usual compensatory increase in insulin release commonly noted in ICU patients. The main site of insulin resistance during stress is at the peripheral tissue level.”
For me, the main clinical take-away point that can be derived from the above quote is that our assumption that elevated blood sugar and dysinsulinism is solely a dietary issue is incorrect. While there is no denying that diet plays a role in most patients, responses to metabolic stressors also play an overwhelmingly important role in creating both the hyperglycemia and insulin resistance we are seeing so often. In turn, when making attempts to optimize blood sugar levels and insulin metabolism, we must go beyond the usual modalities that are solely directed at the optimization of intake and metabolism of dietary carbohydrates.
In concluding the discussion in this section, I would like to suggest one disturbing consideration. The discussion above, as you saw, divides the effects of unstressed starvation and metabolic stress into two neatly defined categories. In fact, it is my guess that this neat division does not accurately portray reality. In contrast, I would hypothesize that in most chronically ill patients we are seeing an additive effect of both processes.
Focusing on protein metabolism
Next, Martindale et al (1) focus more directly on the changes that occur in protein metabolism when subjected to metabolic stress. The authors state:
“The critically ill patient is generally hypercatabolic secondary to marked proteolysis that exceeds protein synthesis.”
The authors continue:
“Marked skeletal muscle catabolism is necessary to provide a substrate for immune function, tissue repair, and inflammation. These processes result in an increase in urea excretion in the urine, which reflects the increased net protein catabolism. The net result is a significant decrease in the lean body mass.”
Before presenting the next quote, I would like to emphasize a key point I made many times over the years in discussing stressed, chronically ill patients. Dietary protein needs go up dramatically over the levels needed to correct simple dietary inadequacy. In turn, in ailing patients, optimal protein intake is much higher than the 0.8 g per kg body weight that is typically suggested in most nutritional texts. In turn, supplementation, often in the form of free form amino acids, is suggested. With the above in mind, consider the following quote:
“Compared to those patients with simple starvation, the protein needs of critically ill and hyperdynamic patients are significantly increased. In concert with muscle proteolysis from the metabolic stress are increased ureagenesis, increased hepatic synthesis of acute phase proteins, increased urinary nitrogen losses, and the increased use of amino acids as oxidative substrate for energy production. Although the accelerated catabolic rate is not reversed by provision of glucose lipid or protein, the protein synthetic rate is at least partially responsive to amino acid infusions. In many cases, nitrogen balance is attained through the support of protein synthesis. Current recommendations for stressed patients are for 15% to 20% of the total nutrient intake to be provided as protein or 1.5 to 2.0 g/kg/d.”
Please note again that, even with protein or amino acid supplementation, the accelerated catabolic physiology cannot be halted with supplementation alone. As I will demonstrate in future newsletters, reduction of inflammation, a key component of Entry Level Clinical Nutrition™, is just as important as optimal macronutrient feeding in slowing accelerated catabolic physiology. In turn, Entry Level Clinical Nutrition™ was designed to be used as seven equally important “spokes in a wheel” so to speak, rather than seven isolated panaceas where focus on any one might yield miraculous results.
Focusing on carbohydrate metabolism
Before presenting the next set of quotes, I would like to state the obvious that, unlike protein, the problem with dietary carbohydrate in most of our chronically ill patients is not deficiency but excessive intake. With this in mind, consider the following:
“In the metabolically stressed adult, the maximum rate of glucose oxidation is 4-6 mg/kg/min, roughly equivalent to 400-600 g/d in a 70 kg person. Provision of glucose greater than this rate usually results in lipogenesis, hepatic steatosis, and hyperglycemia. In the hypermetabolic patient, a significant portion of the oxidized glucose will be derived from endogenous amino acid substrates via gluconeogenesis and from the Cori cycle. In the severely stressed patient, up to one-half of the glucose oxidized may be provided via gluconeogenesis. In the hypermetabolic patient, this endogenous glucose metabolism is not suppressed by exogenous glucose administration.
In fact, providing additional glucose in these situations can lead to significant hyperglycemia with its associated complications.”
The authors continue:
“Complications of excess glucose administration include hyperglycemia, protein glycosylation, hyperosmolar states, immunosuppression, excessive carbon dioxide production associated with increased work of breathing, and hepatic steatosis.”
Before continuing, I would like to emphasize some of the more clinically relevant points of these important quotes:
- Under significant stress, chronically ill patients can only oxidize about 400-600 g or 1600 – 2400 calories of carbohydrate per day. As you know, many patients will be ingesting amounts that are equal or in excess to this, which can cause significant adverse sequelae such as adipose tissue production, fat production in the liver, and increases in serum glucose.
- Given that, in metabolically stressed patients, most of the above oxidized glucose will come from endogenous sources such as gluconeogenesis and the Cori cycle, and given that the addition of exogenous carbohydrate does not slow utilization of endogenous sources, addition of significant amounts of dietary carbohydrate can have disastrous results that include elevated blood sugar and all the complications associated with this. Other disastrous results include increases in hemoglobin A1C, suppressed immunity, and build up of fat in the liver.
With the above in mind, Martindale et al (1) suggest that, even when carbohydrate intake is reduced, it is important to periodically monitor for elevations in blood sugar.
Focusing on lipid metabolism
Concerning alterations in lipid metabolism that occur with significant metabolic stress, Martindale et al (1) state the following:
“In critically ill patients there is an increased rate of fatty acid oxidation. Plasma linoleic and arachidonic acid decrease, while oleic acid increases. This occurs as a result of increased lipolysis that is associated with epinephrine-induced β2-adrenergic stimulation. Free fatty acids are released into the plasma at a rate far exceeding their oxidation. Excess fatty acids undergo hepatic re-esterification, with resultant accelerated hepatic triglyceride formation. The resultant fatty acid profile is consistent with apparent essential fatty acid depletion. In addition, due to the hyperglycemia that often occurs, the elevated insulin levels can reduce lipid mobilization from body fat stores. Thus, in the absence of nutritional fat delivery, a clinical picture of essential fatty acid deficiency can develop earlier than occurs with starvation.”
Since there is a large amount of fairly complicated but clinically important information in the above quote, I would like to emphasize some key points:
- First, under metabolic stress, particularly when associated with increased levels of catecholamines, there is an increase in levels of fat breakdown, resulting in decreases in blood linoleic and arachidonic acids and increases in the monounsaturated oleic acid.
- With metabolic stress, free fatty acids are released from adipose tissue at rates far greater than what can be oxidized. This leads to increases in serum triglycerides. Furthermore, as triglycerides increase, levels of essential fatty acids decrease.
- Given that elevated blood sugar and hyperinsulinemia often accompany these stress related alterations in fat metabolism, it can become more difficult to lose fat from body fat stores.
- Unless additional essential fatty acids are delivered in the diet, the impact of metabolic stress on lipid metabolism can lead to essential fatty acid deficiency.
In turn, due to the above, Martindale et al (1) recommend the provision of lipids to metabolically stressed patients, particularly essential fatty acids:
“Although lipids have their limitations, they remain an important exogenous substrate in critically ill patients as they can facilitate protein sparing, decrease the risk of excess carbohydrate, limit volume delivery by their high caloric density, and provide essential fatty acids.”
How much fat should be provided daily to metabolically stressed patients? The authors state:
“Daily fat when given in moderation can be provided without adverse effects, as critically ill patients efficiently metabolize moderate amounts of exogenous lipids. Fat may comprise between 10% to 30% of total energy requirements.”
Thus, as I hope you can see, it may be a mistake to place a chronically ill patient on a low fat diet.
Focusing on fluid and electrolytes
As I hope I have convinced you by now, focus on fluid and electrolytes such as potassium and magnesium is an incredibly important and, in my opinion, still under appreciated need in chronically ill patients. In turn, for this and other reasons, we usually recommend this as a starting point in Entry Level Clinical Nutrition™. What does Martindale et al (1) have to say on this major issue?
“Critically ill patients have significant gains in total body water compared to normal unstressed individuals.”
“…the hypermetabolic responses to stress also cause avid fluid and salt retention. There is a 15% to 20% increase in the expansion of the extracellular fluid space.”
With this reality in mind, what do the authors recommend in terms of supplementation?
“Fluid and electrolytes should be provided to maintain adequate urine output and normal serum electrolyte concentrations, with emphasis on the intracellular electrolytes, potassium, phosphorus, and magnesium.”
In addition, the authors make the following, usually under appreciated point, about the benefits of electrolyte supplementation:
“Optimal levels are required to maximize protein synthesis and the attainment of nitrogen balance.”
Therefore, as emphasized in Entry Level Clinical Nutrition™, do not just focus on increase protein/amino acid intake and the reduction of inflammation, as many often do, when attempting to increase muscle mass and functional protein synthesis. Optimization of electrolyte balance, which usually involves decreasing sodium intake and increasing potassium and magnesium intake, is equally as important.
How important is it to constantly monitor fluid and electrolyte issues as treatment progresses? The authors state:
“Once nutritional support is initiated, fluid balance, body weight, and electrolytes should be monitored closely as they may change rapidly once adequate protein and calories have been provided and the patient shifts from catabolism to anabolism.”
Of course, to accomplish the above in terms of electrolyte serum testing is optimal. However, given that this is not always practical in the outpatient setting, at least make sure the patient continues to monitor first morning urine pH, which is incredibly easy, practical and cost effective in the outpatient setting.
Focusing on vitamins and minerals
As we all know, the supplement industry and most clinical nutritionists have, for years, made supplementation of vitamins and minerals the foundation of most nutritional therapies. However, as I have suggested earlier in this series, when patient outcome in chronically ill patients is the ultimate determinant of how to proceed clinically, a large body of research is now questioning our tradition of making vitamins and mineral supplementation a necessary “sacred cow” in every patient protocol. For, a large body of research is now legitimately questioning our long held dogma that maintains virtually everyone is deficient and, since these nutrients are “natural,” a little might help and a lot can’t hurt. Therefore, current research is now, more and more, suggesting that vitamin and mineral supplementation is not a central, foundational, nutritional panacea that should be included in abundance in all nutritional protocols but a component of nutritional therapy that is just as important as every other factor just discussed in this newsletter installment. Interestingly, critical care nutritionists have understood for years that vitamin and mineral supplementation is not a panacea but an important part of a comprehensive program. Martindale et al (1) state:
“It is estimated that micronutrient requirements are increased during stress and sepsis due to increased metabolic demands; however, consistent objective data to support universal supplementation are lacking.”
Of course, as suggested earlier in this installment and in Entry Level Clinical Nutrition™, certain selected micronutrients such as zinc, copper, selenium, vitamin D, and iodine are often depleted during metabolic stress and should be measured and, if found to be deficient, supplemented. However, quality, outcome-based research that supports the idea of across-the-board, routine supplementation of all vitamins and minerals is, as suggested by Martindale et al (1) and others, is lacking.
However, with the above being stated, are there situations where doses of micronutrient supplementation significantly above RDA levels are indicated? In another chapter of the same text that contains the Martindale et al (1) chapter, this question is answered. Mason (4) states:
“Certainly there is little debate that supraphysiologic supplementation is indicated for a brief period when a frank deficiency of a micronutrient is identified. As a general guideline, the provision of 5 to 10 times the RDA on a daily basis for 5-7 days, either enterally or parenterally, will suffice as a means of repletion.”
In concluding their chapter on stress physiology, the acute phase response, and their intimate relationship with nutrient metabolism and the role of clinical nutrition in addressing these issues, Martindale et al (1) provide the following summation in their conclusions section. Before presenting this quote, though, I would like to state that the message also very succinctly sums up what I have been trying to present that, first, redefining what we do in this new age of increased illness and scarcity really is incredibly important in terms of improving the rate of successful outcomes which, ultimately, will be the best predictor of successful practices in these financially challenging times. Secondly, the quote sums up my position that only with understanding of the intimate response between nutrient metabolism and how the body responds to stressful situations can we truly reach the higher level of successful outcomes suggested above. The authors state:
“Critically ill or traumatized patients present a unique array of problems for the clinician. As a result of their injury, they are hypermetabolic and hypercatabolic. In addition, there are metabolic alterations to the normal packaging and utilization of nutrients. Nutritional support of these metabolically stressed populations should complement this evolutionary response and should have the objectives of attempting to preserve lean body mass, maintain or up regulate the immune function, and sustain vital organ function while minimizing or averting metabolic complications.”
Of course, as suggested in the next quote, many are of the opinion that the answers to these nutritional needs lie with technological advancements and development of “cutting edge” nutraceutical interventions:
“A litany of novel feeding approaches is now undergoing evaluation, such as preoperative carbohydrate loading, designer enteral formulas, biological mediators such as monoclonal antibodies, and anabolic agents.”
In response to this quote, you may point out that what it suggests are clearly critical care, intensive care unit approaches that would hardly ever find their way into typical outpatient, clinical nutrition practices. Nevertheless, I would suggest that even a casual perusal of the displays of manufacturers who exhibit at the usual symposiums directed towards nutritional practitioners or a quick read of the supplement advertisements that populate journals directed toward nutritional practitioners, to me, makes it clear that our version of what is described in the above quote is becoming more and more common. Specifically, doesn’t it seem like we are seeing more and more high tech, unique extractions or derivatives of sometimes exotic herbs or nutrient forms that are suggested to have panacea-like qualities that can ease the pain and suffering of complex, chronically ill patients because they have an almost magical ability to wash away the “toxins” and other remnants of daily living in our increasingly stressful and biochemically hostile environment? While I must say, in all honesty, that I have great appreciation for these new developments, I must also say, in all honesty, that feedback from many of you suggests that the rate of positive outcomes from these new developments never seems to equal what is promised by the polished marketing materials supplied by the manufacturers. Furthermore, my concerns about this variance between what was promised and what actually occurs in terms of outcome with chronically ill patients are heightened by the sometimes significant cost of these new, “cutting-edge” approaches to nutritional care.
Therefore, the quote from Martindale et al (1) that follows resonates deeply with me, as I hope it does for you, because it emphasizes that, no matter how tempting the research papers and marketing from the developers of these new approaches to clinical nutrition might be, we should still start with the foundational approaches that form the heart of Entry Level Clinical Nutrition™. For, not only are these foundational approaches time-tested and highly efficacious (I’ve lost count how many times I have heard from many of you that correcting electrolyte imbalances with potassium or magnesium, or removing significant allergens such as gluten from the diet, or improving gut function, or optimizing protein intake through diet, free-form amino acids, and/or protein powders led to significant improvements in patient chief complaints), they can lay a vitally important biochemical and metabolic groundwork that will vastly improve the chances of positive outcomes with the new, high-tech products. The authors state:
“However, the basics of nutritional and metabolic support must be addressed before any new and novel approaches are attempted. These basics include early enteral feeding, adequate fluid resuscitation, appropriate protein, calorie, and micronutrient administration…”
In future installments of this series I will present published literature that goes into much greater detail on all the concepts introduced in this discussion of the book chapters by Kushner and Rzewnicki (2) and Martindale et al (1). However, in the next newsletter I will explore in great detail probably the most important and most controversial
assumption made in Entry Level Clinical Nutrition™. In my opinion, it really is true that the physiology and biochemistry that I have highlighted over and over from papers that are specifically designed to address the needs of critical care patients can reliably be applied to the needs of our outpatient, chronically ill patients on a direct, continuous, and ongoing basis.
Moss Nutrition Report #233 – 06/01/2010 – PDF Version
- Martindale RG et al. The metabolic response to stress and alterations in nutrient metabolism. In: Shikora SA et al, ed. Nutritional Considerations in the Intensive Care Unit. Dubuque, IA: Kendall/Hunt Publishing Co.; 2002:11-19.
- Kushner I & Rzewnicki. Acute phase response. In: Gallin JI & Snyderman R, ed. Inflammation: Basic Principles and Clinical Correlations, 3rd Edition. Philadephia: Lippincott Williams & Wilkins; 1999:317-329.
- Ludwig-Beymer P et al. Pain, temperature regulation, sleep, and sensory function. In: McCance KL & Huether SE, ed. Pathophysiology: The Biologic Basis for Disease in Adults and Children, Second Edition. St. Louis: Mosby; 1994:437-476.
- Mason JB. Vitamin and trace elements in the critically ill patient. In: Shikora SA et al, ed. Nutritional Considerations in the Intensive Care Unit. Dubuque, IA: Kendall/Hunt Publishing Co.; 2002:61-77.