Wound healing is a complex, multistep process influenced by a range of modifiable and non-modifiable risk factors. The failure of hard-to-heal wounds to progress to complete healing has been widely studied, and identifying nutritional status is key to achieving optimal wound resolution.
This article discusses the stages of wound healing, the role of macro- and micronutrients in the wound healing journey and the clinical signs of malnutrition. It also highlights screening tools for high-risk groups as well as resources available for the management of malnourished patients, particularly in community settings.
Definition of malnutrition
As defined by the British Association of Parenteral and Enteral Nutrition (BAPEN), malnutrition is a state where there is an imbalance (either deficiency or excess) of energy, protein and other nutrients that adversely affects tissue and bodily functions and clinical outcome (Chen et al, 2001; Johnston, 2007; Cederholm et al, 2017; BAPEN, 2018). Although malnutrition is often considered to be a purely deficient state, it encompasses obesity, and ‘undernutrition’ concerns inadequate nutritional states. For the purposes of this paper, the term ‘malnutrition’ will be used synonymously to mean ‘undernutrition’.
Effects of malnutrition on wound healing
The annual cost of managing wounds to the NHS was estimated to be £5.3 billion, or 4% of total expenditure in 2012–2013 (Guest et al, 2017), while the cost of malnutrition across the population in England was an estimated £19.6 billion in 2011–2012 (Elia, 2015).
Malnutrition adversely affects the physiological response to infection through the loss of immune function, predisposes people to skin infections by rendering the skin thin and friable so more susceptible to wound development, increases the likelihood of pressure wound development through loss of subcutaneous fat over pressure points and increasing immobility through a lack of energy reserves, and reduces the collagen synthesis essential to healing. The financial implications of managing wounds in those who are malnourished are hugely significant (Keys et al, 1950; Stratton et al, 2003; Johnston, 2007; Elia and Russell, 2009; Quain and Khardori, 2015).
Wound healing is a complex process involving a cascade of cellular changes over time. For clinicians, familiarity with the stages of wound healing can aid decision-making regarding the frequency of dressing changes, dressing types and achieving an optimal wound environment. Additionally, an in-depth understanding of the physiological macro- and micronutrient requirements along each stage of the wound-healing process allows for supplementation as individually required. Knowledge of the stages of healing—the inflammatory, proliferative and remodelling phases—and the differing nutritional requirements of each can guide clinical management.
Wound healing is, therefore, a multidisciplinary effort requiring collaboration between clinicians, nursing staff and dietitians.
Phases of wound healing
At the time of injury, the body's physiological response centres on achieving haemostasis through activation of both the intrinsic and extrinsic coagulation cascades. Vasoconstriction and platelet aggregation occur to halt further blood loss (Figure 1). As haemostasis is obtained, the once-vasoconstricted blood vessels dilate, allowing for an influx of inflammatory cells and mediators such as neutrophils and cytokines (Wallace et al, 2020). This initiates the inflammatory phase, which typically lasts for up to 6 days (Quain and Khardori, 2015; Wallace et al, 2020). Neutrophils, monocytes and other inflammatory cells enable phagocytosis and removal of bacteria, ultimately cleaning the wound (Quain and Khardori, 2015).
Simultaneously, fibroblast cells begin paving a collagen network to stabilise the wound and prepare it for epithelisation. Concurrently, angiogenesis (the formation of new blood vessels) occurs. This is known as the proliferative phase and starts in days 5–7.
Approximately 2 weeks after the initial injury, the wound begins to mature, remodelling the collagen formed during the proliferative phase and contracting to minimise the defect. This process takes more than 12 months and is known as the remodelling phase (Johnston, 2007; Quain and Khardori, 2015).
Such descriptions imply wound healing is a linear process, but this is not always the case. Wounds often oscillate between the different phases of healing under the influence of a variety of intrinsic and extrinsic factors. To heal a wound requires significant energy expenditure, up to 35–40 kcal/kg per day (Seiler and Regeniter, 2010), which varies depending on age, comorbid conditions, body weight and level of physical activity. Normally, the body draws on stored energy reserves to meet these requirements but, in malnourished patients, such reserves are depleted if present at all so are unable to meet their bodies' needs to heal. Such considerations require clinicians to manage wounds according to individual needs with an adequate nutritional plan (Molnar et al, 2014; Quain and Khardori, 2015).
Macronutrition, micronutrition and effects of deficiencies in wound healing
Nutritional needs can be subdivided into the macronutritional (protein, carbohydrate and fat) and micronutritional (amino acid, vitamin and mineral) (Quain and Khardori, 2015).
Achieving adequate energy intake through macronutrient delivery, enterally or parenterally, is important, but the distribution of macronutrients is not equal. Traditionally, dietary distribution of macronutrients is 40–60% carbohydrates, 25–30% fat and 15–20% protein but protein needs are increased during all phases of wound healing by up to 250% (Breslow et al, 1993; Molnar et al, 2014). Protein deficiency impairs the proliferative phase by impeding angiogenesis, fibroblast proliferation and collagen production, reducing overall connective tissue formation (Gogia, 1999; Guo and DiPietro, 2010). Carbohydrate deficiency impairs the synthesis of adenosine triphosphate (ATP), further compromising protein synthesis and angiogenesis (Arnold and Barbul, 2006). Fatty acids and cholesterol play important roles in cellular functions such as the formation of cell membranes and insulating nerve axons (Molnar et al, 2014).
Micronutrients' antioxidant properties also play a fundamental role in the process of wound healing. Amino acids such as arginine and glutamine are considered essential amino acids. Arginine, a precursor of nitric oxide, is required in the inflammatory phase and also has roles in collagen synthesis. Glutamine is widely abundant in the human body and also an essential amino acid, with roles in metabolic, enzymatic, immunological and antioxidant processes (Molnar et al, 2014; Quain and Khardori, 2015).
The role vitamins play as enzymatic co-factors in the wound healing process make their adequate intake an additional consideration in nutritional assessments. Deficiences in key vitamins such as vitamin A (retinoic acid), vitamin C (ascorbic acid) and vitamin D have been implicated in prolonging the wound-healing process. For example, vitamin A plays a role in B and T cell function, and is essential particularly during the inflammatory phase of wound healing, while vitamin C assists in collagen synthesis, affecting the proliferative and remodelling phases.
Minerals such as zinc, selenium and iron have all been identified as basic entities required for optimal wound healing by affecting enzymatic function. Zinc plays a role throughout all phases of wound healing, affecting immunity and aiding fibroblast proliferation, collagen synthesis and epithelisation (Johnston, 2007; Lansdown et al, 2007; Acton, 2013; Molnar et al, 2014; Quain and Khardori, 2015).
Identifying risk factors and screening for malnutrition
Malnutrition can be a consequence of starvation, disease, ageing or a combination of all of these factors. Alternatively, it can be classified by whether it occurs in the presence or absence of disease, highlighting its complex and dynamic nature (Cederholm et al, 2017).
Risk factors for malnutrition include reduced oral intake or appetite, decreased thirst response, impairment of taste or smell, dependency on assistance with eating or an overall poorly balanced diet, all of which are commonly experienced by the elderly population (Acton, 2013). Elderly patients are particularly vulnerable owing to comorbidities associated with ageing (such as dementia, stroke and depression) that can affect appetite, as well as the physical ability required to purchase and cook food, lower physical activity and social isolation (Molnar et al, 2014; Quain and Khardori, 2015; Cederholm et al, 2017).
Nutritional assessment of patients is imperative for early identification of those at risk who will be susceptible to delayed wound healing. Early identification of malnutrition, a reversible risk factor, is the basis of the National Institute of Health and Care Excellence (NICE) recommendation for nutritional screening and assessment of all patients on hospital admission, with some studies identifying up to 40% of patients being malnourished on presentation (Stratton et al, 2003; NICE, 2012). It is recommended to re-screen inpatients on a weekly basis using a validated screening tool, or sooner if there is clinical suspicion of malnutrition (NICE, 2012). Such screening is the precursor to a more in-depth nutritional assessment in those who require it, typically conducted in a multidisciplinary team setting led by dietitians.
A number of nutritional screening tools have been developed and more than 70 tools are available (Green and Watson, 2005) in the literature. The Malnutrition Universal Screening Tool (MUST) is a widely used nutritional screening tool in the UK (Brown, 2009). While endorsed by NICE as the screening tool of choice for its practicality, universality, reliability and validity, it is not always easy to implement. Barriers to its use include the need for anthropometric measurements such as weight and height, perceptions of difficulty in use and time constraints (Porter et al, 2009).
MUST categorises patients into being at low, moderate or high risk of malnutrition by taking into account factors such as BMI, weight loss and acute disease (Table 1 and Table 2) (BAPEN, 2006). Further to screening, upon identification of those at risk of undernutrition, a management plan should be completed such as the Managing Adult Malnutrition Pathway (Acton, 2013).
| kg/m2 | Score | % | Score | Score | |||
|---|---|---|---|---|---|---|---|
| Body mass index | >20 | 0 | Weight loss in past 3–6 months | <5% | 0 | Acutely ill AND has been or likely to be no nutritional intake >5 days | 2 |
| 18.5–20 | 1 | 5–10% | 1 | ||||
| <18.5 | 2 | >10 % | 2 |
| Score 0 |
|---|
| Low risk: routine care |
| Score 1 |
| Medium risk: observe |
| Score 2+ |
| High risk: treat |
Nutrition in the community setting
Early identification of people at risk of malnutrition is paramount to prevent wound healing complications. While secondary care dominates the healthcare cost of malnutrition, studies have shown that the majority of malnourished patients live in the community, with data showing only 2% of malnourished patients are in hospital at any given time (Elia and Russell, 2008; Elia, 2015). Therefore, although there are opportunities to implement initial screening in the secondary care environment, continuing care remains a collaborative effort between primary, secondary and tertiary care services.
One recommendation is that all patients undergo nutritional screening on registration with general practice surgeries, at hospital admission or at first outpatient clinic visits and where there is any ‘clinical concern’ (NICE, 2012). Clinical concern should be raised upon identification of any of the previously mentioned risk factors (eg unintentional weight loss, fragile skin, poor wound healing, apathy, cachexia, reduced appetite, altered taste, impaired swallowing, altered bowel habit or prolonged concurrent illness) (NICE, 2012). Once a patient has been identified as malnourished, management includes firstline dietary advice regarding optimisation of oral intake with the use of oral nutritional supplementation as an adjunct if required.
Although mass population screening intuitively seems to be a positive activity, mass screening efforts are time consuming and thus costly in an already overstretched healthcare system. Additionally, nutrition is a dynamic state, and the utility of snapshot ‘mass screening’ results may no longer be applicable when those same patients present again. Perhaps a more tailored approach, where every patient presenting with a documented pathology is screened, may be more cost effective.
Nevertheless, education remains the cornerstone of optimising nutritional intake in the community. Resources include the UK multiprofessional group produced and freely available ‘yellow leaflet’ Your Guide to Making the Most of Your Food for medium-or high-risk groups or the ‘green leaflet’ Eating Well for Low-risk Groups (both available from www.malnutritionpathway.co.uk/leaflets-patients-and-carers). Efforts can also include encouragement to eat small but adequate hydration and overcoming barriers to good nutrition such as isolation, loneliness, poverty, difficulty in cooking and poorly fitted dentures (British Dietetic Association, 2017). Patients should be referred to allied health professionals such as dietitians, occupational therapists, speech therapists and social workers if a mechanical or social barrier to nutrition is identified (Pryke and Lopez, 2013).
Conclusion
Wounds pose a significant burden of disease and cost to the healthcare system, with delayed wound healing a complex, multifactorial issue adversely affected by malnutrition.
Screening those with wounds and early identification of risk factors for malnutrition are vital to ensuring patient nutritional status and requirements are adequately met.
Furthermore, familiarity with the phases of wound healing is paramount to understanding the patient's dynamic nutritional needs, allowing individualised assessment and supplementation of macro- and micronutrients to achieve sufficient caloric intake relative to the phase of wound healing.