Core Topics in General & Emergency Surgery: Companion to Specialist Surgical Practice (79 page)
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Authors: Simon Paterson-Brown MBBS MPhil MS FRCS
Proteins and amino acids
Protein is required for the maintenance of normal health and cellular function. Proteins have many functions, including being essential components of cellular structure. They are required for the synthesis of a variety of secretory proteins produced by many organs. The average daily intake of protein is approximately 80 g in the UK, with a recommended daily intake of 0.8 g/kg body weight and with nitrogen comprising approximately 16% of its weight. However, more than 50% of the world's population exist on less!
Conventionally, amino acids have been classified as either ‘essential’ or ‘non-essential’. The ‘essential’ amino acids cannot be synthesised endogenously and are required in the diet. Paradoxically, the so-called ‘non-essential’ amino acids are actually so metabolically important that humans have retained the ability to synthesise them. Both groups of amino acids are necessary for normal tissue growth and metabolism.
Dietary intake and endogenous synthesis of amino acids in the body maintain the relevant pool of amino acids, replacing those that have been lost by excretion in the urine, losses from the skin and gastrointestinal tract, utilisation as precursors for non-protein synthetic pathways, irreversible modification and irreducible oxidation.
Under certain circumstances (e.g. sepsis, trauma, growth) endogenous synthesis of some amino acids normally considered to be ‘non-essential’ is inadequate; therefore, these amino acids are described as ‘conditionally essential’:
L
-alanine,
L
-glutamate and
L
-aspartate, which are produced by a simple transamination reaction. These are the three most important amino acids in times of starvation:
alanine for hepatic gluconeogenesis;
glutamate as a fuel source for liver, enterocytes and white blood cells;
aspartate for maintaining renal acid–base balance.
Energy transduction is accomplished by the breakdown of carbohydrate, fat and proteins. The energy available from various common nutrients is:
fat 9.3 kcal/g (38.9 kJ/g);
glucose 4.1 kcal/g (17.1 kJ/g);
protein 4.1 kcal/g (17.1 kJ/g);
alcohol 7.1 kcal/g (29.7 kJ/g).
The principal carbohydrates in the diet are polysaccharides (starch and dietary fibre), dextrins and free sugars (monosaccharides), disaccharides, oligosaccharides and sugar alcohols. Dietary fat includes triacylglycerol, containing long-chain fatty acids (C
16
–C
18
triacylglycerols) and medium-chain fatty acids (C
6
–C
12
triacylglycerols) and cholesterol.
If the energy intake of an individual is greater than energy expenditure, extra carbohydrate intake, on reaching the liver via the portal vein, will be channelled into synthesis of glycogen or fat. Glycogenesis dominates until hepatic glycogen stores are replete; thereafter, fat synthesis dominates. Additional fat intake will be stored in adipose tissue as triacylglycerol. In contrast, if there is a negative energy balance, then glycogenolysis dominates until glycogen stores are depleted, then fat and protein will be broken down to provide energy.
Total daily energy expenditure comprises the following:
resting metabolic expenditure (RME), which is energy required for cardiorespiratory function and synthesis and maintenance of electrochemical gradients across cell membranes;
activity energy expenditure (depends on type of physical work undertaken);
diet-induced energy expenditure.
Normally, approximately 25–30 kcal/kg (105–125 kJ/g) are required daily; the magnitudes of changes in requirements in some common conditions are given in
Box 17.2
.
Box 17.2
Additional energy requirements in disease states
Trauma: 0.3 × RME
Elective surgery: 0.1 × RME
Sepsis: up to 0.5 × RME
Severe sepsis: up to 0.6 × RME
Massive burns: 1 × RME
A number of specific organic compounds (vitamins) and inorganic elements are essential for tissue growth and repair, and for maintenance of body function, playing key roles in metabolism, including the processing of macronutrients (protein, carbohydrate and fat). For many micronutrients, specific deficiency diseases have been described. Details of individual substances are beyond the scope of this chapter and can be found elsewhere,
9
but some examples are given in
Box 17.3
.
Box 17.3
Functions of some micronutrients important in surgical practice
Vitamin A
Stabilises epithelial cell membranes; necessary for fibroblast differentiation and collagen secretion
Vitamin D
Role in calcium and phosphate regulation
Vitamin E
Immunostimulant and free radical scavenger
Vitamin K
Required for liver synthesis of clotting factors
Vitamin B
12
Important in synthesis of proteins and nucleic acids
Ascorbic acid
Important in hydroxylation (e.g. collagen synthesis) and energy transduction
Thiamine
Necessary for carbohydrate metabolism and ATP synthesis
Iron
Energy transfer
Copper
Collagen synthesis
Selenium
Antioxidant; protection against peroxidation processes occurring in tissue damage and repair
Zinc
Cofactor in numerous enzymes; necessary for wound healing
In general, micronutrients are classified into:
fat-soluble vitamins (A, D, E and K);
water-soluble vitamins (C and the B vitamins – folic acid, B
12
, B
1
, B
2
, B
3
, pantothenic acid, biotin and B
6
).
trace elements (iron, zinc, copper, selenium, etc.).
The exact requirement for micronutrients during trauma and sepsis is unclear and may alter depending on the type of metabolic support provided.
It should be remembered that micronutrients, if given at high doses, can have toxic effects on tissues. In particular, toxicity can be a problem with excesses of vitamin A, iron, selenium, zinc and copper; vitamin D toxicity is no longer thought to be a significant problem. Care must be taken when these micronutrients are provided for a prolonged period to ensure that toxicity does not occur. It is also unusual to find isolated deficiencies, so identification of one micronutrient deficiency should stimulate consideration of other deficiencies.
It is important to assess the nutritional status in all patients undergoing surgery and identify those who are malnourished, or who are at risk of becoming so. Measurements used previously in clinical practice include:
anthropometric – body structure and composition;
biochemical;
functional – muscle (skeletal and respiratory) and immunological responses.
Height and weight
Height and weight are two commonly used indices of nutritional status.
10
Body weight on its own takes no account of frame size but body mass index (BMI; weight divided by the square of the height) is a good anthropometric indicator of total body fat in adults.
Loss of body weight has been used as an indicator of nutritional status. This is determined by subtracting current weight from recall weight when the patient was ‘well’, or from the ‘ideal’ weight, obtained from published tables. The loss of more than 10% of body weight, or more than 4.5 kg of recall weight, is associated with a significant increase in postoperative mortality. The shorter the period of weight loss, the more significant this is in predicting increased postoperative complications. Malnutrition can be defined as a BMI of less than the 10th percentile with a weight loss of 5% or more.
11
Various techniques for assessing the body's different compartments (e.g. fat, fat-free mass, total body nitrogen and total body mineral contents) have become available but many require specialised equipment and may not be readily applicable to clinical practice. Relatively simple techniques, such as skinfold thickness and bioelectrical impedance, can be used clinically, although even these tend to be used more for research or clinical audits of nutrition and nutritional support.
Skinfold thickness has been used as an index of total body fat (50% of total body fat is subcutaneous, depending on age, sex and fat pad). Triceps skinfold thickness is most commonly measured but assessment of skinfolds at multiple sites is better and correlates with total body fat. Regression equations for the estimation of total body fat from these measurements are available.
12
However, skinfold thickness measurements are susceptible to intra-observer and inter-observer variability, which limits clinical use.
This entails the passage of an alternating electrical current between electrodes attached to the hand and foot. The current passes through the water and electrolyte compartment of lean tissues and the drop in voltage between the electrodes is measured.
13
This change in voltage gives an estimation of total body resistance, which depends principally on total body water and electrolyte content (i.e. lean body mass). This estimate can give an accurate measure of body composition in stable subjects; it becomes less reliable in patients with oedema and electrolyte shifts, and so the value of bioelectrical impedance in critically ill patients remains unclear.
14
Serum proteins
Albumin is the major protein in serum and the relationship between serum proteins and malnutrition was recognised over 150 years ago.
14
Low serum albumin levels are associated with increased risk of complications in patients undergoing surgery.
15
In experimental starvation, however, serum albumin levels may not fall for several weeks
16
because, although synthesis decreases, only 30% of the total exchangeable albumin is in the intravascular space, with the remainder being extravascular. In addition, albumin has a relatively long half-life of approximately 21 days. The flux of albumin between the intravascular and extravascular compartments is about 10 times the rate of albumin synthesis, although this varies greatly depending on capillary permeability.
17
Importantly, serum albumin acts as a negative marker of the acute-phase response, and so is lowered in malignancy, trauma and sepsis, even in the presence of an adequate intake. Serum albumin should therefore
not
be used as an assessment of nutritional
state
, although low levels point to the increased nutritional
risk
associated with underlying disease, and indeed the implied reduction of gut absorption may indicate that the parenteral route may be preferred for provision of nutrition.
Alternatives to using albumin as a marker of nutritional status by measuring other serum protein concentrations, including transferrin (half-life 7 days), retinol-binding protein (half-life 1–2 hours) and pre-albumin (half-life 2 days), have been suggested. The serum levels of these proteins are, however, also altered in stress, sepsis and cancer, and so, as for albumin, they are not useful for assessing nutritional status in routine clinical practice.
Most of the nitrogen lost from the body is excreted in urine, mainly as urea (approximately 80% of total urinary nitrogen). Urea alone may be measured as an approximate indicator of losses, or total urinary nitrogen may be measured, although this latter technique is not widely available. In addition, there are also losses of nitrogen from the skin and in stool of approximately 2–4 g per day. One equation used for balance studies is:
where
Although nitrogen balance has not been shown to be a prognostic indicator, it is a useful way of assessing a patient's nutritional requirements and the response to provision of nutritional support.
Immune competence
In malnutrition there is a reduction in total circulating lymphocyte count and impairment in immune functions, e.g. decreased skin reactivity to mumps,
Candida
and tuberculin (assuming prior exposure), and reduced lymphocyte responsiveness to mitogens in vitro.
18,
19
A correlation between depressed immune function and postoperative morbidity and mortality has been demonstrated, and depression of total circulating lymphocyte count is associated with a poorer prognosis in surgical patients.
20
However, these alterations in immune function are non-specific and affected by trauma, surgery, anaesthetic and sedative drugs, pain and psychological stress,
21
and are not generally applicable to clinical practice.
Skeletal muscle:
Various aspects of skeletal muscle structure and function are deranged in malnutrition. In patients undergoing surgery, handgrip strength (cheap and easy to perform) may predict patients who develop postoperative complications (sensitivity > 90%). However, grip strength is influenced by factors such as patients' motivation and cooperation. Furthermore, such tests may be difficult to apply to critically ill patients. Alternatively, stimulation of the ulnar nerve at the wrist with a variable electrical stimulus results in contraction of the adductor pollicis muscle, the force of which reflects nutritional intake.
22
Respiratory muscle:
The function of the respiratory muscles is impaired by malnutrition and can be detected by deterioration in respiratory function tests, in particular vital capacity.
23
Measurements of inspiratory muscle strength have the advantage that they can be performed in patients who are intubated.
A nutrition risk index is an index of nutritional status based on combinations of variables. Although several indices exist, one that is commonly used depends on serum albumin, current weight and the patient's usual weight:
The score obtained is used to categorise nutritional risk: < 83.5, ‘severe’ risk; 83.5–97.5, ‘mild’ risk; 97.5–100, ‘borderline’ risk. Note that this is a prognostic index and bears little relationship to the patient's nutritional status.
Although the various techniques outlined above can help to predict the risks of complications, there is at present no reliable technique for assessing nutritional status. There is, however, increasing support for using the following techniques, which are applicable to clinical practice.
This simple, yet effective, tool was developed by the British Association for Parenteral and Enteral Nutrition (BAPEN). Details are available from the website, which we recommend you read carefully (
www.BAPEN.org.uk
). This tool has been endorsed by external organisations and its routine use is recommended for all hospital admissions in the UK. As a minimum standard in clinical practice, the MUST tool should be used to assess nutritional risk. Essentially, MUST consists of a series of five steps:
Measure height and weight to obtain BMI (in kg/m
2
) – this is then given a numerical score (> 20 = 0; 18.5–20 = 1; > 18.5 = 2).
Note percentage unplanned weight loss in the previous 3–6 months – then give this a numerical score (< 5% = 0; 5–10% = 1; > 10% = 2).
Establish the ‘acute disease effect’ and also give this a numerical score (if patient is acutely ill and there is or will be no nutritional intake for more than 5 days = 2).
Add scores from steps 1, 2 and 3 together to obtain the ‘overall risk of malnutrition’.
A decision is taken as to what to do depending on the resultant score.
Significance of the resultant score and clinical management:
Score 0 (low risk)
– repeat the screening process at a future time.
Score 1 (medium risk)
– observe by noting the patient's dietary intake for the next 3 days. If this improves then there is little concern. However, if there is no improvement, this is of clinical concern and one should follow the local policies for what to do next, e.g. referral to nutrition support team/dietician.
Score 2 or more (high risk)
– these patients should be referred to the nutrition support team/dietician to try to increase their nutritional intake and there should be policies in place for the nutritional support given to these patients.
The MUST tool should be used routinely to assess nutritional risk for all hospital admissions (
www.BAPEN.org.uk
).
Useful indicators for bedside assessment of nutritional status applicable to clinical practice have been identified,
24
and include estimation of protein and energy balance, assessment of body composition and evaluation of physiological function.
Assessment of protein and energy balance:
Protein and energy balance can be assessed either by a dietician or by a clinician, who determines the frequency and size of meals eaten. This information is compared with the patient's rate of loss of body weight and BMI.
Assessment of body composition:
Loss of body fat can be determined by observing the physical appearance of the patient (loss of body contours) and feeling the patient's skinfolds between finger and thumb. In particular, if the dermis can be felt on pinching the biceps and triceps skinfolds, then considerable weight loss has occurred.
The stores of protein in the body can be assessed from various muscle groups, including the temporalis, deltoid, suprascapular, infrascapular, biceps and triceps, and the interossei of the hands. When tendons of the muscles are prominent and bony protruberances of the scapula are obvious, greater than 30% of the total body protein stores have been lost.
Assessment of physiological function:
Assessments of function are made by observing the patient's activities. Grip strength is determined by asking patients to squeeze the clinician's index and middle fingers for at least 10 seconds, and respiratory function by asking them to blow hard on a strip of paper held 10 cm from the patient's lips. The measurement of metabolic expenditure requires specialised equipment, but additional metabolic stresses on the patient can be determined from clinical examination. Extra metabolic stresses will occur if trauma or surgery has taken place or there is evidence of significant sepsis (elevated temperature and/or white blood cell counts, tachycardia, tachypnoea, positive blood cultures) or active inflammatory bowel disease. In addition, patients should be asked about their ability to heal wounds, changes in exercise tolerance and their ‘tiredness’.
Re-feeding syndrome:
Once a patient's need for nutritional support has been identified, it is important to consider whether the patient is at risk of re-feeding syndrome. This is described in detail elsewhere, but in essence it is the inability of a patient's metabolism to handle macronutrients. After approximately 10 days without nutritional intake, the metabolism adapts to the state of starvation. Re-feeding with full ‘normal’ required amounts of macronutrients will induce a sudden reversal of this adaptation, with an anabolic drive that may result in catastrophic depletion of available potassium, phosphate and magnesium. Before re-feeding, the serum biochemistry may appear ‘normal’, and so the possibility of re-feeding must be anticipated on history alone. The other essential nutrient liable to become depleted in this situation is thiamine, a cofactor of pyruvate kinase, which is required for glucose to undergo oxidative phosphorylation, and without which glucose is metabolised to lactic acid. Thiamine must therefore be replenished before feeding is commenced in the starved patient to prevent development of Wernicke–Korsakoff syndrome. The potential for this is considerably higher in patients with a history of chronic excessive ethanol intake, and so even greater caution is required.
Thiamine deficiency must always be considered in patients who have had no nutritional intake for more than 1 week, who have a history of excessive alcohol intake, or in the presence of an unexplained metabolic acidosis.