NUTRITION AND METABOLIC STRESS
In its never-ending quest to maintain homeostasis, the human body responds to stress, physiologic or psychologic, with a chain reaction that involves the central nervous system and hormones that affect the entire body. Magnitude and duration of the stress determine just how the body will react. It is important for nurses to understand metabolic changes that take place in reaction to stress, both in uncomplicated stress that is present when patients are at nutritional risk, and in more multifarious variations that result from severe stress brought about by trauma or disease.
IMMUNE SYSTEM
One of the first body functions affected by impaired nutritional status is the immune system. When metabolic stress develops, hormonal and metabolic changes subdue the immune system’s ability to protect the body. This activity is further depressed if impaired nutritional status accompanies the metabolic stress. A deadly cycle often develops: impaired immunity leads to increased risk of disease, disease impairs nutritional status, and compromised nutritional status further impairs immunity.
Recovery requires that this cycle be broken.
Overview
Immunity is composed of many cell functions that protect people against the effects of injury or microscopic invasion.
People interact with many other living organisms in the environment.
The size of these organisms varies from large (other humans and animals) to microscopic (bacteria, viruses, molds, spores, pollens, protozoa, and cells from other people or animals).
As long as microorganisms do not enter the body’s internal environment, they pose no threat to health. The body has some defenses to prevent microorganisms from gaining access to the internal environment.
These defenses are not perfect, and invasion of the body’s internal environment by microorganisms occurs often. Invasion occurs much more frequently than does an actual disease or illness because of proper immune functioning.
Purpose of Inflammation and Immunity
The purpose of inflammation and immunity is to neutralize, eliminate, or destroy microorganisms that invade the internal environment. To accomplish this purpose without harming the body, immune system cells use defensive actions only against non-self proteins and cells. Therefore immune system cells can distinguish between the body’s own healthy self cells and other, non-self proteins and cells.
Self Versus Non-Self
Non-self proteins and cells include infected body cells, cancer cells, and all invading cells and microorganisms. This ability to recognize self versus non-self, which is necessary to prevent healthy body cells from being destroyed along with the invaders, is called self-tolerance.
The immune system cells are the only body cells capable of distinguishing self from nonself.
The process of self-tolerance is possible because of the different kinds of proteins present on cell membranes.
All organisms are made up of cells. Each cell is surrounded by a plasma membrane.
With any cell, many different proteins protrude through the plasma membrane.
For example, in liver cells, many different proteins are present on the cell surface (protruding through the membrane).
The amino acid sequence of each protein type differs from that of all other protein types. Some of these proteins are found on the liver cells of all animals (including humans) that have livers, because these protein types are specific to the liver and actually serve as a marker for liver tissues.
Other protein types are found only on the liver cells of humans, because these protein types are specific markers for humans. Still other protein types are found only on the liver cells of humans with a specific blood type.
In addition, each person’s liver cells have surface protein types that are specific to that individual. These proteins are unique to the person and would be identical only to the proteins of an identical twin. These unique proteins, found on the surface of all body cells of that individual, serve as a “universal product code” or a “cellular fingerprint” for that person (Workman, Ellerhorst-Ryan, & Koertge, 1993).
The proteins that make up the universal product code for one person are recognized as “foreign,” or non-self, by the immune system of another person. Because the cell-surface proteins are non-self to another person’s immune system, they are antigens, proteins capable of stimulating an immune response.
This unique universal product code for each person is composed of the human leukocyte antigens (HLAs).
“Leukocyte antigen” is actually an incorrect term, because these antigens are also present on the surfaces of nearly all body cells, not just on leukocytes. HLAs are a normal part of the person and act as antigens only if they enter another person’s body. These antigens specify the tissue type of a person.
Other names for these personal cellular fingerprints are human transplantation antigens, human histocompatibility antigens, and class I antigens.
Humans have about 40 major HLAs (known as histocompatibility antigens) that are determined by a series of genes collectively called the major histocompatibility complex (MHC). However, the exact number of minor HLAs that any person has is not known. The specific antigens that any person has (of a large number of possible antigens) are genetically determined by which MHC genes were inherited from his or her parents.
This universal product code (HLA) is a key feature for recognition and self-tolerance. The immune system cells constantly come into contact with other body cells and with any invader that happens to enter the body’s internal environment.
At each encounter, the immune system cells compare the surface protein universal product codes (HLAs) to determine whether or not the encountered cell belongs in the body’s internal environment.
If the encountered cell’s universal product code (HLA) perfectly matches the HLA of the immune system cell, the encountered cell is considered self and is not attacked by the immune system cell. If the encountered cell’s universal product code (HLA) does not perfectly match the HLA of the immune system cell, the encountered cell is considered non-self, or foreign.
The immune system cell takes action to neutralize, destroy, or eliminate the foreign invader.
Immune function changes during a person’s life, according to nutritional status, environmental conditions, medications, the presence of disease, and age. Immune function is most efficient when people are in their 20s and 30s and slowly declines with increasing age. The older adult has decreased immune function, causing greater susceptibility to a variety of pathologic conditions.
Organization of the Immune System
The immune system is not confined to any one organ or area of the body. The cells of the immune system originate in the bone marrow. Some of these cells mature in the bone marrow; others leave the bone marrow and mature in different specific body sites. After maturation, most immune system cells are released into the blood, where they circulate to most areas of the body and exert specific effects.
The bone marrow is the source of all blood cells, including immune system cells. The bone marrow produces an immature, undifferentiated cell called a stem cell (Guyton & Hall, 2000).
This immature stem cell is also described as pluripotent, multipotent, and totipotent. These terms describe the potential future of the stem cell. When the stem cell is first created in the bone marrow, it is undifferentiated. The cell is not yet committed to maturing into a specific blood cell type. At this stage, the stem cell is flexible and has the potential to become any one of a variety of mature blood cells.
presents a scheme showing the major possible maturational outcomes for the pluripotent stem cell. The type of mature blood cell the stem cell becomes depends on which maturational pathway it follows.
The maturational pathway of any stem cell depends on body needs at the time, as well as on the presence of specific hormones (cytokines, factors, or poietins) that direct commitment and induce maturation.
For example, erythropoietin is made in the kidney. When immature stem cells are exposed to erythropoietin, the immature stem cells commit to following the erythrocyte maturational pathway and become mature red blood cells.
White blood cells (leukocytes) are cells that protect the body from the effects of invasion by foreign microorganisms. These cells are the immune system cells.
The leukocytes can provide protection through a variety of defensive actions (Abbas, Lichtman, & Pober, 1997). These actions include the following:
Recognition of self versus non-self
Phagocytic destruction of foreign invaders, cellular debris, and unhealthy or abnormal self cells
Lytic destruction of foreign invaders and unhealthy self cells
Production of antibodies directed against invaders
Activation of complement
• Production of hormones that stimulate increased formation of leukocytes in bone marrow
Production of hormones that increase specific leukocyte growth and activity
The three processes necessary for immunity and the cell types involved in these responses can be categorized as inflammation;
antibody-mediated immunity (AMI), also known as humoral immunity; and cell-mediated immunity (CMI).
These three processes use different defensive actions, and each process influences or requires assistance from the other two processes.
Therefore full immunity, or immunocompetence, requires the function and interaction of all three processes.
ANTIBODY-MEDIATED IMMUNITY
Antibody-mediated immunity (AMI), also known as humoral immunity, involves antigen-antibody interactions to neutralize, eliminate, or destroy foreign proteins. Antibodies for these actions are produced by populations of В-lymphocytes.
Purpose
The primary functions of B-lymphocytes are to become sensitized to a specific foreign protein (antigen) and to produce antibodies directed specifically against that protein. The antibody (rather than the actual B-lymphocyte) then takes part in one of several actions to neutralize, eliminate, or destroy that antigen.
Immunity
The leukocytes with the most direct role in AMI are the Blymphocytes.
Macrophages and T-lymphocytes cooperate with B-lymphocytes to start and complete antigen-antibody interactions.
Therefore for optimal AMI, the entire immune system must function adequately.
B-lymphocytes start life as pluripotent stem cells in the bone marrow, the primary lymphoid tissue. The pluripotent stem cells destined to become B-lymphocytes commit early to following the lymphocyte maturational.
At the point of commitment these stem cells are no longer pluripotent but are limited to differentiation into lymphocytes. The committed lymphocyte stem cells are released from the bone marrow into the blood. They then migrate into various secondary lymphoid tissues, where maturation is completed.
In humans the secondary lymphoid tissues for B-lymphocyte maturation are the spleen, germinal centers of lymph nodes, tonsils, and Peyer’s patches of the intestinal tract.
Antigen-Antibody Interactions
The body learns to make enough of any specific antibody to provide long-lasting immunity against specific microorganisms or toxins. Seven steps in a series of special interactions are required for the production of a unique and specific antibody directed against a unique and specific antigen whenever the person is exposed to that antigen. These steps are exposure and invasion, antigen recognition, lymphocyte sensitization, antibody production and release, antigen-antibody binding, antibody-binding reactions, and sustained immunity memory.
ANTIGEN RECOGNITION
To begin to make antibodies against an antigen, the “virgin” or previously unsensitized B-lymphocyte must first recognize the antigen as non-self. В-lymphocytes cannot carry out this important function alone; they require the actions of macrophages and helper/inducer T-cells.
This cooperative effort is started by the macrophages. After the membrane of the antigen has been altered somewhat by opsonization, the macrophage recognizes the invading foreign protein (antigen) as non-self and physically attaches itself to the antigen.
This attachment to the antigen does not result in phagocytosis or in immediate destruction of the antigen. Instead, the macrophage presents the attached antigen to the helper/ inducer T-cell. At this time, the helper/inducer T-cell and the macrophage process the antigen in such a way as to expose the antigen’s recognition sites (universal product code).
After processing the antigen, the helper/inducer T-cell brings the antigen into contact with the B-lymphocyte so that the Blymphocyte can recognize the antigen as non-self. virgin B-lymphocyte can undergo sensitization only once.
Therefore each B-lymphocyte can be sensitized to only one antigen.
As a result of sensitization, this B-lymphocyte can respond to any substance that carries the same antigens (codes) as the original antigen. Once it is sensitized to a specific antigen, the Blymphocyte always remains sensitized to that specific antigen.
In addition, all daughter cells of that sensitized B-lymphocyte are sensitized to that same specific antigen.
Immediately after it is sensitized, the B-lymphocyte (or Bblast) divides and forms two different types of lymphocytes, each one remaining sensitized to that specific antigen.
One new cell becomes a plasma cell and immediately starts to produce antibody directed specifically against the antigen that originally sensitized the B-lymphocyte.
The other new cell becomes a memory cell.
The plasma cell functions immediately and has a short life span. The memory cell remains sensitized but functionally dormant until the next exposure to the same antigen.
• LYMPHOCYTE SENSITIZATION
Once the B-lymphocyte recognizes the antigen as non-self, the B-lymphocyte becomes sensitized to this antigen.
ANTIBODY PRODUCTION AND RELEASE
Antibodies are produced by the plasma cell. When fully stimulated, each plasma cell can produce as much as 300 mole tibody specific only to the antigen that originally sensitized the parent B-lymphocyte.
For example, in the case of the baby-sitter who was exposed to and invaded by the chickenpox virus, the plasma cells that are derived from the Blymphocytes sensitized to the chickenpox virus can produce only antichickenpox antibodies. The exact antibody type (e.g., immunoglobulin G [IgG] or immunoglobulin M [IgM]) that the plasma cell can produce may vary, but the specificity of that antibody remains forever directed against the chickenpox virus.
Antibody molecules produced by the plasma cells are secreted into the blood and other extracellular fluids as free antibody.
Individual molecules of free antibody remain in the blood for 3 to 30 days. Because the antibody circulates in body fluids (or body “humors”) and is separate from the Blymphocytes, the immunity provided is sometimes called humoral immunity. Circulating antibodies can be transferred from one person to another to provide the receiving person with immediate immunity of short duration.
ANTIGEN-ANTIBODY BINDING
An antibody is a Y-shaped molecule. The tips of the short arms of the Y are the areas that recognize the specific antigen and bind to it. Because each antibody molecule has two tips (Fab fragments, or arms), antibody molecules can bind either to two separate antigen molecules or to two areas of the same antigen molecule.
The stem of the Y forms what is called the Fc fragment.
This area of the antibody molecule can bind to Fc receptor sites on leukocytes. The leukocyte then has not only its own mechanisms of attacking antigens but also the added power of having antibodies on its surface that stick to antigens.
The actual binding of antibody to antigen is usually not lethal to the antigen. Instead, the physical binding of the antibody to the antigen starts other actions that neutralize, eliminate, or destroy the antigen.
Role of Nutrition
For the immune system to function optimally, adequate nutrients must be available.
A well-nourished body will not be ravaged by infections the way a poorly nourished body will. To prove this point, think of the leading causes of death in industrialized countries such as the United States.
The majority are chronic diseases associated with lifestyle. In developing countries, however, infections lead to high morbidity and mortality rates, especially in children, largely because of the high rate of protein-energy malnutrition (РЕМ). The majority of persons in the United States who have serious problems with malnutrition and infections are
(1) those with severe medical problems,
(2) those who suffer from major metabolic stress,
(3) those who suffer from a diseased state that causes metabolic stress and/or decreased nutrient intake and/or nutrient malabsorption,
and (4) those who have poor nutritional intakes as a result of socioeconomic conditions (e.g., poverty, homelessness).
Compromised nutritional status creates a vulnerable immune system by making it difficult to mount both a stress response and an immune response when confronted with a metabolic stress. A number of nutrients are known to affect immune system functioning.
It is difficult to determine which specific nutrient factor results in symptoms when the patient is malnourished because of overlapping nutrient deficiencies combined with illness and accompanied by weakness, anorexia, and infection.
Immune system components affected by malnutrition include mucous membranes, skin, gastrointestinal tract, T-lymphocytes, macrophages, granulocytes, and antibodies. The effects on the mucous membrane are that the microvilli become flat, which reduces nutrient absorption and decreases antibody secretions. Integrity of the skin may be compromised as it loses density and wound healing is slowed.
Injury to the gastrointestinal tract because of malnutrition may increase risk of infection-causing bacteria spreading from inside the tract to outside the intestinal system.
T-lymphocytes are affected as the distribution of T-cells is depressed. The effect on macrophages and granulocytes requires that more time be needed for phagocytosis kill time and lymphocyte activation to occur. Antibodies may be less available because of damage to the antibody response.
THE STRESS RESPONSE
The body’s response to metabolic stress depends on the magnitude and duration of the stress. Stress sets up a chain reaction that involves hormones and the central nervous system that affects the entire body. Whether stress is uncomplicated (altered food intake or activity level) or multifarious (trauma or disease), metabolic changes take place throughout the body.
According to Gould, the body’s constant response to minor changes brought about by needs or environment was first noted in 1946 by Hans Selye when he described the “fight or flight” response, or general adaptation syndrome (GAS). The body constantly responds to minor changes to maintain homeostasis. Research following Selye’s work has identified that the stress response involves an integrated series of actions that include the hypothalamus and hypophysis, sympathetic nervous system, adrenal medulla, and adrenal cortex.
These responses to stress produce multiple changes in metabolic processes throughout the body. The effect of different levels of stress on metabolic rate is illustrated in Figure 15-1.
Outline two of the body’s responses to stress
The sympathoadrenalmedullary system is the stress pathway involved with acute stress. This is when the higher brain centres have evaluated a situation to be stressful which triggers the hypothalamus, which activates the sympathetic branch of the autonomic nervous system (ANS).
When this branch has been activated we see such symptoms as increased heart rate, heavier and faster rate of respiration and sweaty palms. This then triggers the adrenal medulla to release adrenaline and nor adrenaline into the bloodstream to provide us with energy.
The other bodily response is called the pituitary adrenal pathway and this deals with chronic stress. Once the brain centres are alarmed to stress in the pathway (stressors) the hypothalamus triggers the pituitary gland which releases ACTH into the bloodstream to stimulate the adrenal cortex to release a substance known as cortisol into the bloodstream. The function of cortisol is to maintain a steady supply of blood sugar for continued energy. This enable the body to cope with the stressor, as distinct from the burst of energy needed for ‘fight or flight’.
Starvation
If someone must involuntarily go without food, that can be defined as starvation. If we withhold food from ourselves, such as when we try to lose weight, that can be defined as dieting or fasting.
Whatever the cause of inadequate food intake and nourishment, results are the same. After a brief period of going without food (fasting) or an interval of nutrient intake below metabolic needs, the body is able to extract stored carbohydrate, fat, and protein (from muscles and organs) to meet energy demands.
Liver glycogen is used to maintaiormal blood glucose levels to provide energy for cells. Although readily available, this source of energy is limited, and glycogen stores are usually depleted after 8 to 12 hours of fasting.
Unlike glycogen stores, lipid (triglyceride) stores may be substantial, and the body also begins to mobilize this energy source. As the amount of liver glycogen decreases, mobilization of free fatty acids from adipose tissue increases to provide needed energy by the nervous system.
After about 24 hours without energy intake (especially carbohydrates), the prime source of glucose is from gluconeogenesis.’
Some body cells, brain cells in particular, use mainly glucose for energy. During early starvation (about 2 to 3 days of starvation), the brain uses glucose produced from muscle protein.
As muscle protein is broken down for energy, the level of branched-chain amino acids (BCAA) in circulation increases although they are primarily metabolized directly inside muscle.
The body does not store any amino acids as it does glucose and triglycerides, therefore the only sources of amino acids are lean body mass (muscle tissue), vital organs including heart muscle, or other protein-based body constituents such as enzymes, hormones, immune system components, or blood proteins.
By the second or third day of starvation, approximately
As starvation is prolonged, the body preserves proteins by mobilizing more and more fat for energy. Ketone body production from fatty acids is accelerated, and the body’s requirement for glucose decreases. Although some glucose is still vital for brain cells and red blood corpuscles, these and other body tissues obtain the major proportion of their energy from ketone bodies. Muscle protein is still being catabolized but at a much lower rate, which prolongs survival. During this period of starvation, approximately 60% of the body’s energy is provided by metabolism of fat to carbon dioxide, 10% from metabolism of free fatty acids to ketone bodies, and 25% from metabolism of ketone bodies.
An additional defense mechanism of the body to conserve energy is to slow its metabolic rate, thereby decreasing energy needs. As a result of declining metabolic rate, body temperature drops, activity level decreases, and sleep periods increase— all to allow the body to preserve energy sources. If starvation continues, intercostal muscles necessary for respiration are lost, which may lead to pneumonia and respiratory failure. Starvation will continue until adipose stores are exhausted.
Metabolic Effects of Starvation:
When dietary intake is interrupted, the body turns to endogenous “stored” calories to provide energy for essential functions. Initially, the central nervous system remains dependent on glucose as its primary energy substrate, metabolizing 100 to 150 g/day completely to carbon dioxide and water. If an adequate amount of glucose is not continuously available, a rapid alteration of neuronal activity occurs, characterized by personality changes, confusion, lethargy, and coma. Irreversible neurological damage occurs if carbohydrate deprivation is prolonged for as few as 10 to 20 minutes. The renal medulla, bone marrow, red blood cells, and peripheral nerves are also glucose-dependent, metabolizing a total of 30 to 40 g/day glucose to lactate and pyruvate.
Lactate can be recycled back to glucose through the Cori cycle in the liver and kidney, a process that utilizes energy derived from oxidation of fatty acids. Pyruvate can undergo oxidation with formation of ATP or can serve as a substrate for gluconeogenesis in the liver. Fibroblasts and phagocytes derive much of their energy from the anaerobic metabolism of glucose to lactate.
The liver derives much of its energy from the oxidation of free fatty acids to acetoacetate, acetone, and ß-hydroxybutyrate (the ketone bodies).
The heart, skeletal muscle, and renal cortex, although utilizing glucose for a major share of their energy during normal nutrition, can and do utilize free fatty acids and ketone bodies during starvation. The skeletal muscle also oxidizes the branched-chain amino acids for energy. The gastrointestinal tract utilizes glutamine, oxidizing it to carbon dioxide and water.
Since liver glycogen and extracellular glucose reserves are small, and since muscle glycogen cannot be converted to blood glucose owing to a lack of glucose-6-phosphatase in muscle, humans depend mainly on gluconeogenesis to meet obligatory glucose requirements.
Caloric Equivalents of OrganicComponents in a 70-kg Human
The normal glycolysis pathway.
Although most steps are reversible, three enzymes are necessary for gluconeogenesis to occur. The first is a specific phosphatase capable of converting fructose diphosphate to fructose 6-phosphate. This enzyme is highly active during conditions of fasting, diabetes, and glucocorticoid excess. The increased activity aids in conversion of glycerol from hydrolysis of triglycerides into glucose. Phosphoenolpyruvate carboxykinase catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. This step permits oxaloacetate, and any substance that can be transformed into oxaloacetate, such as aspartate, to serve as substrates for gluconeogenesis. Finally, pyruvate carboxylase catalyzes conversion of pyruvate to oxaloacetate, thereby allowing lactate, alanine, serine, and similar substances to enter gluconeogenesis upon their conversion into pyruvate.
Gluconeogenesis occurs mainly in the liver early in starvation, with the kidney providing up to half of the total glucose produced as starvation continues. The main amino acid substrate for gluconeogenesis in the liver is alanine. Felig and Mallette et al. proposed a glucose-alanine cycle between skeletal muscle and the liver.
The glucose-alanine cycle. (Modified from Mallette, L.E., Exon, J.H., and Park, C.R.: Effects of glucagon on amino acid transport and utilization in the perfused rat liver. J. Biol. Chem., 244:5724-5728, 1969; Felig, P.: The glucose-alanine cycle. Metabolism, 22:179-207, 1973, with permission.)
In muscle, pyruvate is generated from the anaerobic metabolism of glucose. The nitrogen moiety of branched-chain amino acids (valine, leucine, and isoleucine) is transaminated to pyruvate, forming alanine, which is released into the blood. The branched-chain amino acid carbon skeleton is completely oxidized in the muscle to carbon dioxide and water, providing additional ATP for local use. The alanine released from muscle is taken up by the liver, where the nitrogen is split off. The resultant pyruvate is recycled to glucose by gluconeogenesis. Most of the nitrogen is excreted in the urine as urea; however, some is reutilized in protein synthesis. The main substrate for gluconeogenesis in the kidney is glutamine, with other amino acids being converted into it by transamination.
Glutamine as a substrate for gluconeogenesis in the kidney.
The maiitrogenous by-product is ammonia, which is partly excreted in the urine and partly reutilized in protein synthesis.
Early in starvation, approximately
Lipolysis, which increases as serum insulin concentrations fall with starvation, releases free fatty acids and glycerol. Although free fatty acids cannot participate directly in gluconeogenesis, they can serve as an energy source in the liver for the Cori cycle and generate acetyl-CoA, which enhances the conversion of pyruvate to oxaloacetate. Glycerol is readily converted to glucose but provides only about
With prolonged starvation there is a gradual decrease in total body energy expenditure.
This decreased metabolic activity is manifested by diminished muscle activity, increased sleep, and decreased core temperature. In addition to a decrease in metabolic rate, the need for gluconeogenesis diminishes, mainly as the result of the conversion of the central nervous system to utilization of ketone bodies for energy rather than glucose. The stimulus for this adaptation is unknown, although it may be in part caused by the rise in serum alanine or ketone body concentrations or by the lowered serum molar ratio of insulin to glucagon. Protein catabolism falls from 75 to 20 g/day, with a marked decrease in excretion of urea nitrogen to 3 to 5 g/day
In fully adapted starvation, protein catabolism provides as little as 5 percent of the total daily calories. With decrease in gluconeogenesis, adipose tissue becomes even more important as an energy substrate, with 60 percent of the total caloric expenditure derived from metabolism of fat to carbon dioxide, 10 percent from conversion of free fatty acids to ketone bodies, and 25 percent from metabolism of ketone bodies by peripheral tissues. Serum ketone body concentrations increase with the increased fat metabolism and eventually exceed the renal threshold. Metabolic acidosis is not present. The appearance of ketone bodies in the urine is the hallmark of the physiological response to prolonged starvation. It is in this adapted state that humans can best tolerate prolonged fasting, perhaps for 60 to 70 days.
Survival from prolonged starvation is dependent on body reserves and the severity of the caloric deficit. Click HERE for a program to calculate days to survival during inadequate nutrition support.
The provision of fluid requirements as 5 percent dextrose solutions, long advocated to decrease proteolysis and starvation ketosis, has recently come under question.
The actual effect of administration of 100 to
Endocrine Response to Starvation:
Endocrine responses to starvation are often complex.
Hormonal Changes in Various States of Nutrition
To simplify this discussion, the endocrine response is divided into substances enhancing catabolism, those stimulating anabolism, and those influencing fluid and electrolyte balance. The degree of stimulation and the relative potency of each hormone determine the overall host response.
Catecholamines: The adrenalin response to stress and injury was first described by Cannon in 1939. The two catecholamines, epinephrine and norepinephrine, are secreted following a large variety of stimuli, including excitement, fear, anger, tissue injury, and fractures. Epinephrine, which is secreted only by the adrenal medulla, stimulates hepatic glycogenolysis and gluconeogenesis, inhibits secretion of insulin, inhibits uptake of glucose by peripheral tissues, favors release of amino acids from muscle, and directly stimulates hydrolysis of fat. Norepinephrine, produced throughout the body at nerve synapses and also by the adrenal medulla, has less marked metabolic activity but does stimulate hydrolysis of fat. As the result of their extremely short biological half-lives, the metabolic effects of catecholamines are transient, lasting only 24 to 48 hours.
During starvation, secretion of catecholamines is decreased, reducing their impact on metabolic activity. In addition, there is reduced catecholamine-stimulated glucagon release from the pancreas and adrenocorticotropic hormone from the pituitary gland, resulting in lowered glucocorticoid and aldosterone secretion.
Glucocorticoids: Corticoid production decreases during starvation. The reduced corticoid production favors lipogenesis and results in less inhibition of protein synthesis, less stimulus for the mobilization of amino acids from skeletal muscle, and increased renal tubular reabsorption of amino acids. In addition, there is less induction of transaminating enzymes for gluconeogenesis, less suppression of insulin secretion, and less release of glucagon. The stimulus for conversion of lactic acid to glycogen and protection of the lysosomal membrane against pH changes is also reduced.
During starvation or hyperglycemia, blood levels of human growth hormone may be elevated two to three times above normal. Human growth hormone is produced by the acidophilic cells of the anterior pituitary gland. It stimulates nitrogen, phosphorus, and potassium retention, and also lipolysis, fatty acid oxidation, and ketogenesis. Growth hormone antagonizes the actions of insulin, depressing glucose uptake by muscle and elevating blood glucose levels. It also stimulates synthesis of chondroitin sulfate and collagen. Infusion of amino acids (especially arginine) strongly stimulates growth hormone secretion even in the absence of fasting.
Little change is seen in androgen production during starvation. Testosterone is considered the major androgen. The normal female produces 0.34 mg/day, and the male 7 mg/day. This hormone has potent anabolic activity, stimulating retention of nitrogen, potassium, phosphorus, and calcium and increasing lean body and visceral protein masses. It may also function to decrease amino acid catabolism.
Secretions of the pancreatic islet cells play a major role in the regulation of body fuel metabolism. Insulin, secreted by the beta cell, functions as a potent anabolic hormone.
It promotes storage of exogenous glucose, inhibits gluconeogenesis and glycogenolysis, strongly inhibits lipolysis, and favors protein synthesis. In contrast, glucagon, secreted by the pancreatic alpha cell, is a potent catabolic hormone. It acts to prevent hypoglycemia by stimulating gluconeogenesis, glycogenolysis, proteolysis, and lipolysis. The pancreatic delta islet cells are interposed between the alpha and beta cells and regulate both by secretion of the inhibitory hormone somatostatin. The interreactions between the pancreatic islets cells result in very precise glucose homeostasis. The absolute concentrations of insulin and glucagon appear not to be as important in glucose homeostasis as the insulin:glucagon molar ratio. Following an overnight fast, the insulin:glucagon molar ratio is only slightly depressed from its normal level of about 4.0, slightly favoring gluconeogenesis. Further starvation, up to 6 to 8 days, is associated with a marked depression of the ratio to as low as 0.4, strongly favoring catabolism. The increased glucagon secretion is felt to play a prominent role in stimulating the glucose-alanine cycle as discussed above. With prolonged starvation there is an increased production of ketone bodies which in turn stimulate the release of insulin. As insulin inhibits lipolysis, there is a feedback control preventing severe ketosis. In addition, the increased insulin secretion raises the insulin:glucagon molar ratio, limiting the rate of catabolism.
Ion-diabetic subjects, infusion of carbohydrate results in an increased insulin:glucagon ratio to as high as 70, whereas infusion of amino acids decreases it. The simultaneous infusion of hypertonic dextrose and amino acids, as in total parenteral nutrition, results in an overall increase in the insulin:glucagon ratio, favoring anabolism.
Certain diseases may be associated with hyperglucagonemia, which makes the establishment of anabolism during parenteral nutrition more difficult. Glucagon is cleared from the plasma by the liver and the kidneys. In either hepatic or renal failure, decreased glucagon clearance can become significant. Further, diabetic patients often demonstrate baseline hyperglucagonemia, an exaggerated release of glucagon with protein meals, and a paradoxical increase in glucagon with carbohydrate infusion.
Fluid and Electrolyte Balance:
Uncomplicated starvation is associated with only small increases in aldosterone secretion, whereas the major fluid shifts of trauma may result in marked increases. Aldosterone decreases renal excretion of sodium and bicarbonate, while increasing potassium losses. By increasing sodium ion concentrations in the serum and thus serum osmolarity, the extracellular fluid volume is increased. Aldosterone secretion is increased by catecholamines and hyponatremia. In addition, isotonic hypovolemia stimulates renin release by the renal juxtaglomerular apparatus. This promotes angiotensin formation, which in turn stimulates aldosterone release.
Antidiuretic Hormone:
Antidiuretic hormone inhibits free-water clearance by the kidneys. Clinical situations associated with hypovolemia or hyperosmolality stimulate the release of antidiuretic hormone, which results in an increase in intravascular volume and decrease in osmolality.
As discussed previously, the two hormones of fluid and electrolyte balance respond primarily to decreased intravascular volume and decreased serum osmolality. After prolonged malnutrition, patients often are markedly dehydrated, with depleted intravascular volumes. Initiation of parenteral nutrition in these patients may be associated with marked initial fluid retention until the intravascular volume is replenished. Solution formulas reflecting normal serum electrolyte content are most effective in replacing the intravascular volume; hypotonic electrolyte solutions are contraindicated and can lead to the syndrome of inappropriate antidiuretic hormone secretion with excessive shifting of fluid into extravascular spaces.
Normal total body protein synthesis occurs at a rate of approximately 18 to 30 g/day. It is, therefore, possible to predict the approximate time required for metabolic recovery by dividing the estimated total deficit by the average daily gain. The actual time required to replace all protein losses is somewhat longer than calculated, since maximum anabolism is not immediately obtained or always maintained. During recovery, essential amino acid, total protein, and caloric requirements all are greater thaormal. After nitrogen losses have been restored, fat is gained almost exclusively for several weeks or months until the normal body fat stores are regained. In this phase, nitrogen balance is zero, although carbon balance is positive.
This section has dealt with the metabolic effects of short- and long-term starvation. An understanding of these metabolic processes, as well as needs for vitamins, electrolytes, and minerals, is critical for effective administration of nutritional support. Every effort should be made to recognize losses of body mass caused by starvation and to avoid significant nutritional depletion by providing adequate nutritive support. If nutritional support is provided before marked wasting occurs, an anabolic state is more easily obtained and maintained.
Severe stress
Whether stress is accidental (e.g., from broken bones or burns) or necessary (e.g., from surgery), the body reacts to these stresses much as it does to the stress of starvation—with a major difference.
During starvation, the body’s metabolic rate slows, becoming hypometabolic. During severe stress, the body’s metabolic rate rises profoundly, thus becoming hypermetabolic.
The ebb phase, or early phase, begins immediately after the injury and is identified by decreased oxygen consumption, hypothermia (lowered body temperature), and lethargy. The major medical concern during this time is to maintain cardiovascular effectiveness and tissue perfusion. As the body responds to injury, the ebb phase evolves into the flow phase, usually about 36 to 48 hours after injury.
The flow phase is characterized by increased oxygen consumption, hyperthermia (increased body temperature), and increased nitrogen excretion, as well as expedited catabolism of carbohydrate, protein, and triglycerides to meet the increased metabolic demands. The flow stage will last for days, weeks, or months until the injury is healed.
Ebb Phase
¨Immediate—hypovolemia, shock, tissue hypoxia
¨Decreased cardiac output
¨Decreased oxygen consumption
¨Lowered body temperature
¨Insulin levels drop because glucagon is elevated.
Flow Phase
¨Follows fluid resuscitation and O2 transport
¨Increased cardiac output begins
¨Increased body temperature
¨Increased energy expenditure
¨Total body protein catabolism begins
¨Marked increase in glucose production, FFAs, circulating insulin/glucagon/cortisol
Multiple stresses result in increased catabolism and even greater loss of body proteins. Unfortunately, some stresses that patients are obliged to endure are iatrogenic. Think, for example, of the series of stresses a patient admitted for elective surgery might experience.
Preoperatively, most surgical patients receive only clear liquids or nothing by mouth (NPO). After surgery, they may remain NPO until the return of bowel sounds, then progress through clear- and full-liquid diets until they can tolerate food.
If the patient is in poor nutritional status before the stress of surgery, he or she is at greater risk to develop pneumonia or a wound infection accompanied by fever as a result of decreased protein synthesis. As in starvation, energy requirements will be met from endogenous sources if exogenous sources are not available or adequate.4 Thus intercostal muscles may be depleted, leading to pneumonia, or inadequate amino acids may be available to synthesize antibodies, leading to impaired immune response to infection. Either complication has a negative impact on metabolic demands.
Nutrients affected by hypermetabolic stress include protein, vitamins, and minerals, as well as related nutritional concerns for total energy and fluid intake. During moderate metabolic stress, protein requirements have been reported to increase from 0.8 gm/kg body weight (amount recommended for an average healthy adult) to 1.0 to 1.5 gm/kg body weight and for severe stress (e.g., thermal injuries exceeding 20% total body surface area) can rise to 1.5 to 2.0 gm/kg body weight.
These levels are based on sufficient energy consumption to allow for protein synthesis.
Requirements of vitamins and minerals all increase during stress.
Tissue repair especially depends on adequate intakes of vitamin C, zinc, calcium, magnesium, manganese, and copper.
At the least, Dietary Reference Intake (DRI) levels of nutrients should be consumed, preferably from foods rather than from vitamin or mineral supplements.
Achieving requirements through food intake also supports provision of sufficient kcalories to meet increased energy demands during critical illness.
Several formulae have been used to determine energy needs of patients experiencing hypermetabolic stress.
One formula (Harris-Benedict) takes into account basal energy expenditure (BEE), activity level, and severity of injury. Activity level considers energy required if the patient is confined to bed or is ambulatory. Severity of injury is a factor based on whether the injury is caused by major or minor surgery, mild to severe infection, skeletal or blunt trauma, or burns (based on percentage of body surface area affected).
Registered dietitians, in collaboration with the medical team, use these formulas to determine energy requirements. As factor assessments change, nurses can alert either the registered dietitian or other members of the medical team to ensure adequate energy provision.
Fluid need during hypermetabolic stress is based on age, reflecting age-related modifications of body composition. For adults younger than 55 years old, fluid needs are calculated at 35 to 40 ml/kg body weight. Adults between the ages of 55 to 75 years require a lower amount, 30 ml/kg body weight; and for adults older than age 75, 25 ml/kg body weight is recommended.
Starvation vs. Stress
¨Metabolic response to stress differs from the responses to starvation.
¨Starvation = decreased energy expenditure, use of alternative fuels, decreased protein wasting, stored glycogen used in 24 hours
¨Late starvation = fatty acids, ketones, and glycerol provide energy for all tissues except brain, nervous system, and RBCs
¨Hypermetabolic state—stress causes accelerated energy expenditure, glucose production, glucose cycling in liver and muscle
¨Hyperglycemia can occur either from insulin resistance or excess glucose production via gluconeogenesis and Cori cycle.
¨Muscle breakdown accelerated also
Hormonal Stress Response
¨Aldosterone—corticosteroid that causes renal sodium retention
¨Antidiuretic hormone (ADH)—stimulates renal tubular water absorption
¨These conserve water and salt to support circulating blood volume
¨ACTH—acts on adrenal cortex to release cortisol (mobilizes amino acids from skeletal muscles)
¨Catecholamines—epinephrine and norepinephrine from renal medulla to stimulate hepatic glycogenolysis, fat mobilization, gluconeogenesis
Cytokines
¨Interleukin-1, interleukin-6, and tumor necrosis factor (TNF)
¨Released by phagocytes in response to tissue damage, infection, inflammation, and some drugs and chemicals
Systemic Inflammatory Response Syndrome
¨SIRS describes the inflammatory response that occurs in infection, pancreatitis, ischemia, burns, multiple trauma, shock, and organ injury.
¨Patients with SIRS are hypermetabolic.
Venn diagram showing overlap of infection, bacteremia, sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction.
Multiple Organ Dysfunction Syndrome
¨Organ dysfunction that results from direct injury, trauma, or disease or as a response to inflammation; the response usually is in an organ distant from the original site of infection or injury
Diagnosis of Systemic Inflammatory Response Syndrome (SIRS)
¨Site of infection established and at least two of the following are present
—Body temperature >38° C or <36° C
—Heart rate >90 beats/minute
—Respiratory rate >20 breaths/min (tachypnea)
—PaCO2 <
—WBC count >12,000/mm3 or <4000/mm3
—Bandemia: presence of >10% bands (immature neutrophils) in the absence of chemotherapy-induced neutropenia and leukopenia
¨May be caused by bacterial translocation
Bacterial Translocation
¨Changes from acute insult to the gastrointestinal tract that may allow entry of bacteria from the gut lumen into the body; associated with a systemic inflammatory response that may contribute to multiple organ dysfunction syndrome
¨Well documented in animals, may not occur to the same extent in humans
¨Early enteral feeding is thought to prevent this
Bacterial Translocation across Microvilli and How It Spreads into the Bloodstream
Hypermetabolic Response to Stress—Cause
Hypermetabolic Response to Stress—Pathophysiology
Effects of Stress on Nutrient Metabolism
Protein Metabolism
Even if adequate carbohydrate and fat are available, protein (skeletal muscle) is mobilized for energy (amino acids are converted to glucose in the liver). There is decreased uptake of amino acids by muscle tissue, and increased urinary excretion of nitrogen.
Some nonessential amino acids may become conditionally essential during episodes of metabolic stress. During stress, glutamine is mobilized in large quantities from skeletal muscle and lung to be used directly as a fuel source by intestinal cells.11 Glutamine also plays a significant role in maintaining intestinal immune function and enhancing wound repair by supporting lymphocyte and macrophage proliferation, hepatic gluconeogenesis, and fibroblast function.
Carbohydrate Metabolism
Hepatic glucose production is increased and disseminated to peripheral tissues although proteins and fats are being used for energy. Insulin levels and glucose use are in fact increased, but hyperglycemia that is not necessarily resolved by the use of exogenous insulin is present. This appears, to some extent, to be driven by an elevated glucagominsulin ratio.
Fat Metabolism
To support hypermetabolism and increased gluconeogenesis, fat is mobilized from adipose stores to provide energy (lipolysis) as the result of elevated levels of catecholamines along with concurrent decrease in insulin production.10 If hypermetabolic patients are not fed during this period, fat stores and proteins are rapidly depleted.
This malnutrition increases susceptibility to infection and may contribute to multiple organ dysfunction syndrome (MODS), sepsis, and death.
Hydration/Fluid Status
Increased fluid losses can result from fever (increased perspiration), increased urine output, diarrhea, draining wounds, or diuretic therapy.
Vitamins and Minerals
Just as kcaloric needs increase during hypermetabolic conditions, so too do needs for most vitamins and minerals. And if kcalorie needs are met, the patient will most likely receive adequate amounts of most vitamins and minerals. Special attention, however, should be given to vitamin С (ascorbic acid), vitamin A or beta carotene, and zinc.12 Vitamin С is crucial for the collagen formatioecessary for optimal wound healing. Supplements of 500 to 1000 mg/day are recommended.
Vitamin A and beta carotene (vitamin A’s precursor) also play an important role in the healing process in addition to their role as antioxidants. Zinc increases the tensile strength (force required to separate the edges) of a healing wound. Supplements of 50 to 75 mg/day (orally) when stable are commonly used.12 Additional zinc may be necessary if there are unusually large intestinal losses (small bowel drainage or ileostomy drainage).
Protein-Energy Malnutrition
Inadequate intake of energy, particularly from protein, can result in acute or chronic protein deficiency, or protein-energy malnutrition (РЕМ). РЕМ can be primary or secondary. Primary РЕМ is the result of inadequate intake of nutrients.
Secondary РЕМ results from inadequate nutrient consumption caused by some disease state that impairs food consumption, interferes with nutrient absorption, or increases nutritional requirements.
Malnutrition, the imbalance of nutrient intake, encompasses conditions that range from over-consumption of nutrients to extreme under-consumption. This discussion concerns the conditions related to under-consumption of nutrients. Underconsumption can result iutrient deficiencies that range from marginal to severe starvation. Marginal deficiencies occur when lower than recommended levels of nutrients are regularly consumed. Although obvious signs of specific nutrient deficiencies may not be visible, the level of wellness and ability to function at an optimum level are compromised. As the other nutrient categories of vitamins and minerals are studied, specific symptoms of deficiencies will be explored.
Starvation has become a catch-all term. Although we may say “I’m starving” when we’ve missed a meal, our starvation io way compares with that experienced by those who truly do not have access to sufficient quantities of high-quality food. The technical term for starvation is protein-energy malnutrition (РЕМ). РЕМ is an umbrella term for malnutrition caused by the lack of protein, energy, or both.
РЕМ affects populations around the world. This form of malnutrition is responsible for about half of the 10.9 million child deaths per year. Of children with РЕМ, 70% are found in Asia, 26% in Africa, and 4% in Latin America and the Caribbean Islands. In young children, РЕМ can cause permanent disabilities because most brain growth occurs during the early years of life. Extreme РЕМ results in the conditions of marasmus and kwashiorkor. These disorders can be fatal because of decreased resistance to infections; the body, lacking protein, is unable to create sufficient quantities of antibodies to support the immune system.
Marasmus is malnutrition caused by a lack of sufficient energy (kcalorie) intake.
An individual with marasmus is extremely thin; skin seems to hang on the skeletal bones. Fat stores that normally fill out the skin have been used for energy to maintain minimum body functioning. Muscle mass is also reduced, having also been used for energy, and nutrients are not available to rebuild it. If the condition continues, damage may occur to major organs such as the heart, lungs, and kidneys. Marasmic children will not grow. If the condition occurs between 6 and 18 months of age, the time during which the most brain development occurs, permanent brain damage may result.
In contrast to marasmus, the symptoms of kwashiorkor give the appearance of more than sufficient fat stores in the stomach and face.
Kwashiorkor is malnutrition caused by a lack of protein while consuming adequate energy.
The swollen belly and full cheeks of kwashiorkor are caused by edema (water retention).
Edema occurs because protein levels in the body are so low that protein is not available to maintain adequate water balance in the cells and fluid accumulates unevenly.
When adequate nutrition is provided, the fluid is no longer retained. Instead of a full belly and round cheeks, the loss of fat stores becomes apparent and the skin hangs loosely, similar to marasmus. An individual with kwashiorkor is apathetic and experiences muscle weakness and poor growth.
Without sufficient protein, lipids produced by the liver are unable to leave and thus accumulate there. The liver becomes fatty and unable to function well. Even hair quality is affected because protein is the main constituent of hair. Curly hair becomes straight, hair falls out easily, and the pigmentation changes.
The definition of kwashiorkor is evolving. Kwashiorkor was identified as a disorder that develops when very young children are switched from breast milk to solid foods. Although they are consuming enough kcalories, it seems that their protein intake is too low for the needs of their growing bodies. Based on these observations, kwashiorkor is defined as malnutrition caused by protein deficiency although adequate energy is consumed.
This definition, however, does not explain why other children and adults in the same community develop marasmus instead of kwashiorkor. As researchers continueto study the disorder, they have noticed similarities between the locations where kwashiorkor is prevalent and where exposure to dietary aflatoxin occurs.
They have also noted that that the symptoms of kwashiorkor are similar to those of aflatoxin poisoning. Aflatoxin is a mold that develops when grains are stored under poor conditions of heat and humidity. Eating grains affected by aflatoxin can affect liver function, even leading to liver cancer.
The liver produces NEAAs, without which protein synthesis throughout the body is limited. If liver function is reduced, as with aflatoxin poisoning, production of protein-related structures and substances is decreased. Compared with healthier children and adults, it appears that when malnourished children consume aflatoxin-tainted grains, their weakened immune systems are not able to fight off the effects of aflatoxin. Aflatoxin also induces immunosuppression, creating a cumulative effect that may lead to the development of kwashiorkor
Malnutrition Factors
Malnutrition is often caused by several factors that affect food availability. Although poverty tends to be a dominant influence, other forces also affect the development of malnutrition. These include biologic, social, economic, and environmental factors.
Biologic factors affect the ability of the body to use nutrients. Economic effects encompass the ability to purchase food and also consider the structure of a country’s economy and access to employment. Environmental factors directly affect the availability of food as related to crop production and food safety. Lack of education, social isolation, and the rippling effects of underemployment seem to be malnutrition factors throughout the world, regardless of the overall wealth of nations.
Health and economic support systems provided throughout the life cycle may prevent the development of factors affecting food availability.
Marasmus-Kwashiorkor Mix
This combined form of РЕМ develops when acute stress (surgery or trauma) is experienced by someone who has been chronically malnourished.13 The condition becomes life threatening because of the high risk of infection and other complications.
It is important to determine whether marasmus or kwashiorkor is predominant so appropriate medical nutrition therapy can be initiated. The undernourished, unstressed (hypometabolic) patient is at risk of complications such as those observed in refeeding syndrome, and the stressed patient at risk for kwashiorkor is more likely to suffer from underfeeding.
Nurses can be key players in the recognition and prevention of any of the different forms of РЕМ. By being alert to clinical signs and laboratory values seen in kwashiorkor and marasmus, further deterioration of the patient’s nutritional status can be prevented.
MULTIPLE ORGAN DYSFUNCTION SYNDROME
Multiple organ dysfunction syndrome (MODS) involves the progressive failure of two or more organ systems at the same time (e.g., the renal, hepatic, cardiac, or respiratory systems). It may occur following trauma, severe burns, infection, or shock, usually results from an uncontrolled inflammatory response, and can progress to organ failure and death.
MODS commonly begins with lung failure followed by failure of the liver, intestine, and kidney.16 Myocardial failure generally manifests later, but central nervous system changes can occur at any time.
The pathogenesis of MODS is complex but usually results in the initiation of the stress response and release of catecholamines,14 producing a hypermetabolic state in the patient. Higher levels of kcalories and protein are necessary to meet increased metabolic demands. How patients are fed is also important. Early enteral feedings (Chapter 14) appear to maintain gut mucosal mass and barrier function and promote normal enterocytic growth in the gut.13-17 .
SURGERY
In a perfect world, all patients undergoing surgery would be at optimal nutritional status to help them tolerate the physiologic stress of the surgery and temporary starvation that follows. But, all too often, surgical patients may be malnourished secondary to the medical condition causing the need for surgery. Additionally, they may experience anorexia, nausea, or vomiting, which decrease their ability to eat.
Fever may increase their metabolic rate. Or nutritional needs may not be met because of malabsorption. For surgery to be successful, patients who are malnourished or in danger of malnutrition must be identified so corrective action may be arranged. Before surgery, patients are typically limited to NPO to prevent aspiration.
Oral intake is generally resumed when bowel sounds return, usually 24 to 48 hours after surgery. The postoperative diet usually progresses from clear liquid to solid foods as tolerated.
BURNS (THERMAL INJURY)
Pathophysiology of Burn Injury
The tissue destruction caused by a burn injury can cause many local and systemic problems, including fluid and protein losses, sepsis, and disturbances of the metabolic, endocrine, respiratory, cardiac, hematologic, and immune systems. The extent of local and systemic disruption is related to many factors, including age, general health status, extent of injury, depth of injury, and area of body injured. Even after healing, the burn injury can cause late complications such as contracture formation and extensive scarring. Therefore the prevention of infection and closure of the burn wound are vitally important.
A lack of or delay in healing is a key factor for all systemic disturbances and is responsible for much morbidity and mortality among clients who are burned.
Integumentary changes resulting from burn injury
Anatomic changes
The skin is the largest organ of the body.
Each of its two major layers, the epidermis and dermis, has several sublayers. The epidermis, the outer layer of skin, is a superficial layer of stratified epithelial tissues approximately
The depth of the dermal appendages varies considerably across body areas. The sweat and oil glands in the palm of the hand and the sole of the foot, for example, extend deep into the dermis. This allows for healing of fairly deep burns in these areas. The epidermis has no blood vessels and receives nutrients by diffusion from the second layer of skin, the dermis.
The basement membrane, a thioncellular protein surface, separates the dermis from the epidermis. The dermis is sometimes called the “true skin” because it is not constantly shed and replaced; it is thicker than the epidermis and ranges in thickness from 0.60 to
When burn injury occurs, the skin can regenerate as long as parts of the dermis are present. When the entire layer of dermis is burned, all epithelial cells or dermal appendages are destroyed, and the skin cao longer regenerate spontaneously.
The subcutaneous tissue, or superficial fascia, varies in thickness and lies below the dermis. With deep burns, the subcutaneous tissues may be damaged, leaving bones, tendons, and muscles exposed.
Functional Changes
The skin serves multiple functions. The skin is primarily a protective barrier against injury and microbial invasion from the environment. A burn injury breaks this barrier, greatly increasing the risk for infection.
The skin also helps maintain the delicate fluid and electrolyte balance essential for life. After a burn injury, massive fluid loss occurs through evaporation. Water vapor can evaporate through burn-injured skin four times as rapidly as from intact skin. The rate of evaporation is proportional to the total body surface area burned and the depth of injury.
Skin is important in thermoregulation. Normally the body can adjust to most fluctuations in environmental temperatures because subcutaneous fat provides insulation and because blood flow to the skin changes with these fluctuations in environmental temperature. When the skin is damaged, the body cannot adjust to the loss of heat as readily, and body temperature tends to decrease.
The skin functions as an excretory organ through perspiration.
Full-thickness burns destroy the sweat glands, which results in a loss of excretory ability.
The skin is the largest sensory organ of the body. Pain, pressure, temperature, and touch are sensed on the skin in normal daily activities, which allows a person to react to changes in the environment. All burn injuries are painful.
With partial-thickness burns, nerve endings are exposed to the surface, which causes an increased sensitivity and a subsequent increase in pain. With full-thickness burns, nerve endings are completely destroyed. Initially these wounds are completely anesthetic (do not transmit sensation) when a sharp stimulus is applied. Despite this destruction, clients often complain of a dull or pressure-type of pain in these areas.
Skin exposed to sunlight produces vitamin D. The conversion of cholesterol derivatives into the active form of vitamin D is completed in the skin. Partial-thickness burns reduce the activation of vitamin D; this conversion is lost completely in full-thickness burns.
The skin is an important determinant of physical identity. The skin’s cosmetic quality contributes to each person’s unique appearance. With a change in appearance through a major burn, severe psychologic problems may develop.
Temperature
The temperature of the body’s internal environment falls within a narrow range (approximately 84.2° to 109.4° F [29° to 43° C]) compared with the wide temperature fluctuations in the external environment. The body has several mechanisms to compensate for wide variations in external temperature. Circulating blood both provides and dissipates heat. Heat dissipation is efficient under normal conditions.
When heat is applied to the skin, the temperature of the immediate subdermal layer rises rapidly. As soon as the heat source is removed, the body’s compensatory mechanisms quickly return the area to a normal temperature. If the heat source is not removed, or if it is applied at a rate or level that exceeds the skin’s capacity to dissipate it, cellular destruction occurs.
The skin can tolerate temperatures up to 104° F (40° C) without sustaining injury.
At temperatures of 158° F (70° C) and above, cell destruction is so rapid that brief periods of exposure damage the skin down to and including the subcutaneous level.
Depth of burn injury
The magnitude of a burn injury is based on the depth and extent of the total body surface burn. The degree of tissue destruction is determined by what agent specifically caused the burn and by the temperature and duration of exposure to the heat source.
Variations in skin thickness over different parts of the body also influence burn depth. In areas where the epidermis and dermis are thin (e.g., eyelids, ears, nose, genitalia, tops of the hands and feet, fingers, and toes), a short exposure to extreme temperatures can result in a deep burn injury.
The skin is thinner in older adults, which predisposes them to increased burn severity, even at lower temperatures of shorter duration.
Burn wounds are classified as superficial-thickness wounds, partial-thickness wounds, full-thickness wounds, and deep fullthickness wounds. The partial-thickness wounds are further separated into superficial and deep subgroups. Table 68-1 characterizes the clinical differences of these burns.
The American Burn Association (ABA) describes burns as minor, moderate, or major depending on the depth, extent, and location of injury.
Superficial-thickness wounds.
Of all burn types, superficial-thickness wounds have the least destruction because the epidermis is the only portion of the skin that is injured.
The basal epithelial cells and basement membrane— structures necessary for the total regeneration of epithelial cells—remain present.
Superficial-thickness wounds often result from prolonged exposure to low-intensity heat (e.g., sunburn) or short (flash) exposure to high-intensity heat. Erythema with mild edema, pain, and increased sensitivity to heat occurs as a result. Peeling of dead skin (desquamation) occurs for 2 to 3 days after the burn, and the area rapidly heals in 3 to 5 days without a scar. No significant clinical consequences occur at this level of injury.
FIG.1. Superficial burns on the trunk and right arm of a young child. Typically, these are red burns that blanch with pressure.
PARTIAL-THICKNESS WOUNDS.
A partial-thickness wound involves the entire epidermis and varying depths of the dermis. Depending on the amount of dermal tissue damaged, partial-thickness wounds are further subdivided into superficial partial-thickness and deep partial-thickness injuries.
SUPERFICIAL PARTIAL-THICKNESS WOUNDS.
Superficial partial-thickness wounds result from either increased duration or increased intensity of exposure. These wounds are typically erythematous and moist.
The classic vesicle (blister) forms as the stratum corneum and stratum granulosum are destroyed. When intact, the blister forms a sterile environment, which protects the wound from potential infection and excess water loss. However, large or numerous blisters are opened to promote healing and prevent immunosuppression.
Superficial partial-thickness wounds result in increased pain sensation. Nerve endings are exposed to the surface, and any stimulation (touch or temperature change) causes intense pain. With standard treatment these burns heal in 10 to 14 days with no scar, but some minor pigment changes may occur.
FIG. 2. Superficial partial-thickness burn on a man’s right knee. Blistering wounds that blanch with pressure are characteristic of superficial partial-thickness burns. These wounds are also typically moist and weeping.
DEEP PARTIAL-THICKNESS WOUNDS.
Deep partialthickness wounds extend deeper into the dermal layer of the skin, and fewer healthy epidermal cells remain. The wounds usually appear red and waxy white without blisters.
Edema is moderate; pain is present to a lesser degree than with superficial burns because more of the nerve endings have been destroyed. Blisters are absent because the dead tissues adhere to the underlying dermal collagen fibers.
The remaining blood supply to these areas is greatly reduced due to intense vasoconstriction. Progression to deeper injury can occur through hypoxia and ischemia. Adequate hydration, nutrients, and oxygen are necessary for spontaneous re-epithelialization of the wound and the prevention of conversion to deeper burns. Partial-thickness wounds can convert to full-thickness wounds when tissue damage increases with infection, hypoxia, or ischemia.
Deep partial-thickness wounds generally heal in 3 to 6 weeks, but a large amount of scar formation results. Surgical intervention with skin grafting is required if healing will be prolonged.
FIG. 3. Deep partial-thickness burns on the trunk and extremities of a young child. These burns are typified by easily unroofed blisters that have a waxy appearance and do not blanch with pressure.
FULL-THICKNESS WOUNDS.
A full-thickness wound involves the entire epidermal and dermal layers of the skin.
No living (viable) epidermal cells remain for re-epithelialization, and skin grafts are required in areas larger than approximately 12 to 16 cm2. In smaller areas, secondary wound closure occurs by the growth of collagen-based scar tissue from the unburned edges inward .
The area of full-thickness injury has a hard, dry, leathery eschar (burn crust) that forms from coagulated particles of destroyed dermis.
FIG. 4. Full-thickness burn on a woman’s left flank. Burn areas of this type are characteristically insensate and waxy white or leathery gray in color.
The eschar is dead tissue; it must slough off or be removed from the burn wound before healing can occur.
The thick, coagulated particles often adhere to the subcutaneous layer by collagen fibers, which makes the removal of eschar difficult. Edema is a significant problem in burns and is pronounced under the eschar in a full-thickness wound.
When the injury completely surrounds an extremity or the thorax (circumferential), circulation and ventilation may be compromised by tight eschar.
Escharotomies (incisions through the eschar) or fasciotomies (incisions through eschar– and fascia) may be required to relieve pressure and allow normal perfusion and breathing (see Surgical Management.
The color of a full-thickness burn wound may be waxy white, deep red, yellow, brown, or black. Thrombosed vessels may be present and visible beneath the surface of the burn because the dermal blood vessels are heat coagulated, causing the burned tissue to be without a blood supply (avascular).
Sensation is minimal or absent in these areas of injury due to the destruction of nerve endings. Healing time depends on the re-establishment of an adequate blood supply within the injured areas and can range from weeks to months.
DEEP FULL-THICKNESS WOUNDS.
Deep lullthickness wounds extend beyond the skin into underlying fascia and tissues. These deep injuries damage muscle, bone, and tendons and leave them exposed to the surface.
These burns occur with flame, electrical, or chemical injuries.
The wound is blackened and depressed, and sensation is completely absent.
All full-thickness burns benefit from early excision and grafting. Grafting decreases pain and length of stay and accelerates recovery (Ramzy et al., 1999). Amputation may be required when an extremity is involved.
VASCULAR CHANGES RESULTING FROM BURN INJURIES
Major circulatory disruption occurs at the burn site immediately after a burn injury. The vessels supplying the burned skin are occluded, and blood flow through the arterial and venous channels decreases or ceases completely. Damaged macrophages within the tissues release chemicals (mediators) that initially produce vasoconstriction. Peripheral vessel thrombosis may occur; this decrease in tissue perfusion can cause necrosis, which can lead to deeper injuries in the already damaged areas.
• Fluid Shift
After the initial vasoconstriction, vessels adjacent to the burn injury dilate. This leads to increased capillary hydrostatic pressure and is accompanied by increased capillary permeability .
This fluid shift, also known as third spacing or capillary leak syndrome, involves a continuous leak of plasma from the intravascular space into the interstitial space. The loss of plasma fluids and proteins results in a decreased colloidal osmotic pressure in the vascular space.
Leakage of fluid and electrolytes from the vascular space continues, causing significant edema formation. Fluid shift usually occurs in the first 12 hours after the burn but can continue for 24 to 36 hours.
The amount of plasma to interstitial fluid shift depends on the extent and severity of injury. Capillary leak occurs in both burned and unbumed tissues when tissue damage is extensive (i.e., greater than 20% to 30% total body surface area [TBSA]).
Peripheral edema develops as the protein-rich fluids, plasma, and electrolytes escape into the interstitial space.
Tissue colloidal osmotic pressure increases as a result of the movement of proteins, increasing the third-spacing fluid shift.
Profound imbalances of fluid, electrolytes, and acid-base occur as a result of the fluid shift and other physiologic disruptions caused by injury.
These imbalances usually include hypovolemia, metabolic acidosis, hyperkalemia (elevated blood potassium levels), and hyponatremia (decreased blood sodium levels). Hyperkalemia occurs as a result of direct tissue damage that releases large amounts of intracellular potassium into the vascular space; it is generally self-limiting.
Hemoconcentration (elevated blood osmolarity, hematocrit, and hemoglobin) develops from the circulatory dehydration.
Hemoconcentration increases blood viscosity, which reduces flow through small vessels and contributes to generalized tissue hypoxia
Fluid Remobilization
The inflammatory responses gradually subside 24 to 36 hours after the injury, and the capillary leak abates. Fluid shifts back into the circulation. This fluid remobilization phase restores fluid and electrolyte levels and renal blood flow, resulting in increased urine formation and diuresis.
Body weight returns to normal over several days as peripheral edema subsides.
During this phase, hyponatremia is likely to develop because of increased renal sodium excretion and the loss of sodium from wounds. Hypokalemia can occur now as potassium returns to the intracellular compartment.
Anemia often develops as a result of hemodilution, but it is generally not severe enough to require blood transfusions. Transfusions are indicated if the client’s hematocrit is less than 20% to 25% and is accompanied by clinical signs and symptoms of hypoxia.
The exact laboratory value is not as critical as the clinical signs and symptoms. The timing of transfusions is controversial, and the trend is to limit transfusion unless absolutely necessary
Metabolic changes resulting from burn injury
A significant burn injury places the client in a hypermetabolic state. Increased secretion of catecholamines, antidiuretic hormone, aldosterone, and cortisol increase metabolism.
With hypermetabolism, oxygen and calorie requirements are high.
The secreted catecholamines activate the stress response.
The increased production (and loss) of heat results in protein and fat breakdown (catabolism), the rapid use of glucose and calories, and increased urinary nitrogen losses. The evaporated heat and water from the burn also increase metabolic
and catabolic rates, which increase calorie expenditure. Depending on the extent of injury, the client’s calorie requirements may be double or triple normal energy needs. These increased rates peak 4 to 12 days after the burn and can remain elevated for months until all wounds are closed.
The hypermetabolic condition also results in an increase in core body temperature. The client loses heat through the burned skin surfaces because the protective barrier is lost. Core body temperature increases as a response to the adjustment in the hypothalamus. Central thermoregulation is altered to compensate for the hypermetabolic state. There is an impaired shift in temperature; a low-grade fever can develop, which is common among clients with burn injuries. Essentially what occurs is a resetting of the body’s normal temperature-regulating mechanism.
• IMMUNOLOGIC CHANGES RESULTING FROM BURN INJURY
Thermal injury results in a loss of the protective barrier of the skin, which increases the risk for infection. The burn injury activates the inflammatory response but can also suppress immune function. Antibody-mediated immunity and cell-mediated immunity are both suppressed. All immune responses are therefore reduced. Topical antimicrobial agents, systemic antibiotics, general anesthesia, blood component transfusion, and the stress of surgical procedures further compromise immune function.
Burns are customarily defined as tissue destruction that results in circulatory and metabolic alterations that require the compensatory response to injury.
Actual cause of burns may be thermal or nonthermal, such as chemical, electrical, or radioactive sources. Thermal burns are usually characterized as contact (hot solid object), flame (direct contact with flames), or scald injuries (heated liquid).
These events have significant effects outritional status.
Burns are generally classified by physical appearance and symptoms associated with the affected skin14 and are often described in terms of percent of body surface burned.
First-degree burns (or partial thickness injury) involve only the epidermis, resulting in simple reddening of the area with no injury to underlying dermal or subcutaneous tissue.
Sunburns are an example of first-degree burns caused by ultraviolet radiation damage to skin.
First-degree burns heal within 3 to 5 days without scarring.
Seconddegree burns (superficial partial-thickness injury and deep partial-thickness injury) involve two categories of burn depth with distinctly different characteristics. Superficial partial-thickness burns are characterized by redness and blistering that affect epidermis and some dermis.
Deep partial-thickness burns are characterized by destruction of epidermis and dermis (resulting in a waxy, white, mottled appearance), leaving only skin appendages such as hair follicles and sweat glands.
Second-degree burns take weeks to months to heal.
Third-degree burns (full-thickness injury) are characterized by destruction of the entire epidermis, dermis, and frequently the underlying subcutaneous tissue. Occasionally, muscle or bone tissue may be destroyed.
In addition to pain management, wound care, and infection control, nutrition support is recognized as one of the most significant considerations of patient care. The first 24 to 48 hours of treatment for burn patients are dedicated to replacement of fluid and electrolytes. Fluid needs are based on the patient’s age, weight, and extent of the burn.
Total body surface area (TBSA), used to estimate the extent of the burn, can be estimated using the “rule of nines”
Thermal injury wounds will heal only if the patient is in an anabolic state. Therefore, feeding should be initiated as soon as the patient has been hydrated.
Very early enteral feeding (within 4 to 12 hours of hospitalization) has been shown to be successful in decreasing the hypercatabolic response, decreasing the release of catecholamines and glucagon, reducing weight loss, and shortening the length of the hospital stay.
Several methods may be used to estimate energy and proteieeds in burn patients. Energy needs vary according to the size of the burn. One of the simplest and easiest to use is the Curreri formula (adults):
kcal needed per day X [25 kcal X kg usual body weight (kg)] + [40 kcal X % TBSA burned]
Estimates using the Curreri formula may exceed actual energy needs, but it is not uncommon for a patient to need 4000 to 5000 kcalories. Another method is to calculate BEE (Harris-Benedict) and multiply by a factor of 1.5 to 2.O.15
Protein lost through urine and wounds, increased protein use for gluconeogenesis, and wound healing increase proteieeds in burned patients.16 It is therefore important that kcalories from protein are not calculated into total energy needs. Carbohydrates and fats are good for protein sparing (nonprotein energy sources).
Whether a patient receives adequate amounts of energy or protein is best evaluated by wound healing, graft take, and basic nutritional assessment parameters.
In conjunction with increased energy demands, vitamin and mineral needs are generally increased in burn patients, but exact requirements are not known.
Most patients will receive vitamins in excess of the recommended intake because of their high kcaloric intakes, but special consideration should be given to vitamin С (collagen synthesis, immune function) and vitamin A (immune function and epithelialization).
Supplements are commonly recommended.
Nutritional Management
NUTRITIONAL ASSESSMENT
¨Traditional methods not adequate/reliable
¨Urine urea nitrogen (UUN) excretion in gms per day may be used to evaluate degree of hypermetabolism:
–0 –5 = normometabolism
–5 – 10 = mild hypermetabolism (level 1 stress)
–10 – 15 = moderate (level 2 stress)
–>15 = severe (level 3 stress)
¨Clinical judgment must play a major role in deciding when to begin/offer nutrition support
Determination of Nutrient Requirements
•Energy
•Protein
•Vitamins, Minerals, Trace Elements
•Nonprotein Substrate
–Carbohydrate
–Fat
Energy
•Enough but not too much
•Excess calories:
–Hyperglycemia
•Diuresis – complicates fluid/electrolyte balance
–Hepatic steatosis (fatty liver)
–Excess CO2 production
•Exacerbate respiratory insufficiency
•Prolong weaning from mechanical ventilation
Energy
•Enough but not too much
•Excess calories:
–Hyperglycemia
•Diuresis – complicates fluid/electrolyte balance
–Hepatic steatosis (fatty liver)
–Excess CO2 production
•Exacerbate respiratory insufficiency
•Prolong weaning from mechanical ventilation
Indirect Calorimetry
•Better estimate in critically ill hypermetabolic patient
•The “gold standard” in estimating energy needs in critical care
•Can be used in both mechanically ventilated and spontaneously breathing patients (ventilated patients most accurate)
•Equipment is expensive and not readily available in many facilities
SUMMARY
The stress response of the body also affects nutritional status. Whether the stress response is caused by physiologic or psychologic determinants, the entire body is affected. Metabolic changes take place in reaction to stress. This includes changes caused by uncomplicated stress that is present when patients are at nutritional risk and severe stress caused by trauma or disease. The functioning of the immune system is also affected by the hormonal and metabolic changes that occur when metabolic stress develops. The immune system’s ability to protect the body is further depressed if impaired nutritional status accompanies the metabolic stress.
