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The Harm Scale

Caroline Fife suggested I should publish a simple scale for tissue damage and call it the “Harm Scale”.

Here it is.

Analysing wounds requires to have a look at it at five levels, from the molecule up to the social environment of the patient. To understand events in wounded cells and tissue, it is important to realise that cells and tissues have a range of states related to damage. The linguistic problem is that damage is considered as, well, damage but in reality, cell and tissue damage ranges from no damage to death. Therefore, perhaps, we may refer to the scale as loss of homeostasis. Here the normal state means there is no loss of homeostasis, and the dead state means there is a maximum loss of homeostasis. This also makes sense because the body considers homeostasis the optimum and any loss of homeostasis will evoke a reaction. But the easiest option is, as Caroline pointed out, to use the word harm, which can be seen as a measure of loss of homeostasis.

What is harm?

Harm stands for how much problems a cell or a tissue has in its normal function.

Logically a cell or tissue can be in six states of harm:

  1. Normal,
  2. Adapted,
  3. Stressed,
  4. Injured,
  5. Damaged,
  6. Dead.

 

Normal is the normal state, where the cell or a tissue is well adapted to the circumstances and it is able to fulfil its required role. Here, the cell and tissue are in a state homoeostasis.

Adapted, if there are changes in the environment, cells or tissue adapt by changing its anatomy, physiology or behaviour. Adaptation causes cells and tissues to communicate their changed state with their environment, and the body detects those signals (Pakos‐Zebrucka et al. 2016; Erguler, Pieri, and Deltas 2013)

Stressed, when the changes lead to problems in the cells or tissue’s anatomy, physiology or behaviour becomes stressed. Here it is no longer able to fulfil all its activities normally. Stressed cells and tissues start sending out distress signals like reactive oxygen species, HIF-1a and other signals (Andreeva et al. 2015; Bohovych and Khalimonchuk 2016). These signals are not only detected by the body but some signals can also be detected in laboratory analysis (Görlach et al. 2015; Pichu et al. 2018).

Injured, if the changes have led to small-scale damage, like a leaking cell membrane or tissue damage, problems can begin to arise. Leaking for instance ATP and calcium through membranes and other forms of damage (DAMPS) are interpreted as unwelcome events (Horn and Jaiswal 2018; Tang and Marshall 2017). This implies that the signals resulting from cell and/or tissue injury may already elicit an inflammatory response (Jagannathan and Tucker-Kellogg 2016; Rathinam and Chan 2018). Often injury may be repaired, allowing for full regeneration.

Damaged, if the resultant harm has led to irreversible, yet non-lethal, damage, there are inevitable consequences. For example, loss of a limb, may not kill you, but it will reduce your functionality. The body will detect damage and respond. It might do so by apoptosis, the controlled killing of damaged cells (Karch and Molkentin 2015). IApart from liver or skin tissue, full regeneration of damage is not an option. Here the negative consequence of fibrotic repair can take place (Whyte, Smith, and Helms 2012; Greaves et al. 2013; Nyström and Bruckner-Tuderman 2018).

Dead, a dead cell is, well … dead. If a dead cell or tissue is not cleaned up properly, but is destructed instead, it’s organelles and DNA function as a danger signal, the so-called DAMP’s (danger associated molecular patterns) invoking inflammation and other tissue repair or regeneration processes (Pandolfi et al. 2016; Maslanik et al. 2013).

The Harm Scale has dimensions of level, size and time. A single cell moving up the Harm Scale, does not imply that the tissue containing that cell is also adapted, injured or damaged. The tissue it is in,  might very well be in perfect homeostasis. However, if more cells in the tissue start to get damaged or die, in time the tissue itself may start moving on the Harm Scale. And similarly, if a tissue is moving up the Harm Scale does not mean your body or parts of it are damaged.

Nevertheless, an inflammatory response is always imminent, inflammation is good but at the price of remaining scars, even at the molecular level (Fulop et al. 2018). Chronic inflammation is a source for age-related disease. (Franceschi et al. 2018)

So, even if harm doesn’t necessarily lead to direct damage, even little harm may cause problems over time in the li=ong run (Ashcroft, Mills, and Ashworth 2002).

 

Why is this important?

The body detects and responds to any deviation from homeostasis and will react to regain homeostasis. If the reaction is insufficient, the tissue damage will increase in size and magnitude and cause serious problems for the patient.

If you consider most non-traumatic wounds result from an underlying condition, the Harm Scale begins to make sense. It draws attention to the pre-clinical events which impact the clinical events to follow. If the harm is not handled properly, you are setting up your topical treatment for failure.

Flatly, if you fail to recognise the obstructed vessel, your dressing is not going to do much.

Even stressed cells may already have an impaired ability to handle harm, this condition may worsen if the harm moves up the scale. If the surrounding cells or tissues are in a grave state, the situation can spiral out of control, like in the case of skin failure at the end of life (Levine 2016).

Recognising the existence of harmed tissue highlights how a patient, who does not yet have a wound, might still suffer enough from harm to develop a wound in the near future. Or even worse, a closed wound does not mean there is no tissue damage, setting the stage for recurrence.

Neglecting the level of harm in tissue, can cause to you take action which may result in an avoidable lesion. (Black et al. 2011)

The Harm Scale also points out that, not only the tissue in the wound but also the cells and tissue surrounding the wound may be harmed, impairing the ability to repair or regenerate tissue. In general, it will be safe to say that processes, like proliferation, will take place outside the wound, even perhaps outside of the inflamed zone (Park et al. 2017). This means that the quality of the surrounding tissue plays an important role in the wound healing process.

Figure 1 Schematic representation of harm in and outside the wound.

In this paper we treat the Harm Scale at level 2 of the Five Level Model for Wound Analysis and Treatment. The five level model is a system to describe factors influencing the cause and resolution of wounds at a normal (0), general (1), local (2), systemic (3) and cellular-molecular (4) level. The levels represent a connection between where problems occur and common clinical and scientific practice. (Smit 2018)

Level 2 is local, the level of the wound. However, the Harm Scale also exists at other levels, examples are:

  • Level 1; inflammaging (Chen et al. 2014),
  • Level 3; organ-system damage (San Miguel-Ruiz and García-Arrarás 2007) and
  • Level 4; (epigenetic) DNA damage (Nanduri, Semenza, and Prabhakar 2017; Jasiulionis 2018).

Using the Harm Scale at all 5 levels opens up the possibility of making use of preventive and curative toolkits used in other types of tissue damage like renal, brain or heart damage. It also allows us to make use of the insights from inflammation research, like inflammaging (Castellani et al. 2016).

 

How the Harm Scale can help.

In today’s wound care we only casually touch on the subject of tissue damage, because the most used solution for a wound is a dressing. The Harm Scale may help us in evaluating tissue in, under and around wounds.

Having some kind of definition of harm will improve communication on the complexities of the state tissues and cells are in. Acquiring a better understanding of the level of harm in tissue allows us for assessment and modalities to maintain homeostasis.

It may be helpful to notice that, though adapted, stressed, injured and damaged cells signal their harm state to their environment, the body can under- or over-react. If the patient is compromised these early signals may be missed, masking what is really happening. On the other hand, if injured, damaged and dead cells invoke a dramatic response, this in itself, may spiral out of control in a compromised patient.

The Harm Scale is also helpful in determining where to inject growth factors, miRNA’s and other interventions. Zones in which cells are barely surviving maybe not the best place for your intervention. You have to locate the proper location in, around and under the wound for a (maximal) effect (Berlanga et al. 2013).

Perhaps, if we start diagnosing and treating issues which reduce the body’s ability to repair or regenerate tissue, we might find better ways to predict and/or prevent wounds. A Harm Scale type assessment can be a useful addition to the toolbox.

And in the process, we will learn how to achieve much better results from our current treatment modalities.

© Harm Smit (2018)

Ps. It is really weird, writing a text like this when your name is … Harm.

 

References

Andreeva, Elena R., Margarita V. Lobanova, Olga O. Udartseva, and Ludmila B. Buravkova. 2015. “Response of Adipose Tissue-Derived Stromal Cells in Tissue-Related O2 Microenvironment to Short-Term Hypoxic Stress.” Cells Tissues Organs 200 (5): 307–15. https://doi.org/10.1159/000438921.

Ashcroft, Gillian S, Stuart J Mills, and Jason J Ashworth. 2002. “Ageing and Wound Healing.” Biogerontology 3 (6): 337–45. https://doi.org/5100237 [pii].

Berlanga, Jorge, D V M Ms, José I Fernández, Ernesto López Ms, Pedro a López, Amaurys Río, Carmen Valenzuela Ms, et al. 2013. “Heberprot-P: A Novel Product for Treating Advanced Diabetic Foot Ulcer.” Medic Review 15: 11–15. https://www.ncbi.nlm.nih.gov/pubmed/23396236

Black, Joyce M, Laura E Edsberg, Mona M Baharestani, Diane Langemo, Margaret Goldberg, Laurie McNichol, Janet Cuddigan, and National Pressure Ulcer Advisory Panel. 2011. “Pressure Ulcers: Avoidable or Unavoidable? Results of the National Pressure Ulcer Advisory Panel Consensus Conference.” Ostomy/Wound Management 57 (2): 24–37. http://www.ncbi.nlm.nih.gov/pubmed/21350270.

Bohovych, Iryna, and Oleh Khalimonchuk. 2016. “Sending Out an SOS: Mitochondria as a Signaling Hub.” Frontiers in Cell and Developmental Biology 4 (October): 109. https://doi.org/10.3389/fcell.2016.00109.

Castellani, Gastone C., Giulia Menichetti, Paolo Garagnani, Maria Giulia Bacalini, Chiara Pirazzini, Claudio Franceschi, Sebastiano Collino, et al. 2016. “Systems Medicine of Inflammaging.” Briefings in Bioinformatics 17 (3): 527–40. https://doi.org/10.1093/bib/bbv062.

Chen, Pei-Yu, Lingfeng Qin, Zhen W Zhuang, George Tellides, Irit Lax, Joseph Schlessinger, and Michael Simons. 2014. “The Docking Protein FRS2α Is a Critical Regulator of VEGF Receptors Signaling.” Proceedings of the National Academy of Sciences of the United States of America 111 (15): 5514–19. https://doi.org/10.1073/pnas.1404545111.

Erguler, Kamil, Myrtani Pieri, and Constantinos Deltas. 2013. “A Mathematical Model of the Unfolded Protein Stress Response Reveals the Decision Mechanism for Recovery, Adaptation and Apoptosis.” BMC Systems Biology 7: 16. https://doi.org/10.1186/1752-0509-7-16.

Franceschi, Claudio, Paolo Garagnani, Paolo Parini, Cristina Giuliani, and Aurelia Santoro. 2018. “Inflammaging: A New Immune–metabolic Viewpoint for Age-Related Diseases.” Nature Reviews Endocrinology. https://doi.org/10.1038/s41574-018-0059-4.

Fulop, Tamas, Anis Larbi, Gilles Dupuis, Aurélie Le Page, Eric H. Frost, Alan A. Cohen, Jacek M. Witkowski, and Claudio Franceschi. 2018. “Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?” Frontiers in Immunology 8 (January). https://doi.org/10.3389/fimmu.2017.01960.

Görlach, Agnes, Katharina Bertram, Sona Hudecova, and Olga Krizanova. 2015. “Calcium and ROS: A Mutual Interplay.” Redox Biology 6: 260–71. https://doi.org/10.1016/j.redox.2015.08.010.

Greaves, Nicholas S., Kevin J. Ashcroft, Mohamed Baguneid, and Ardeshir Bayat. 2013. “Current Understanding of Molecular and Cellular Mechanisms in Fibroplasia and Angiogenesis during Acute Wound Healing.” Journal of Dermatological Science 72 (3): 206–17. https://doi.org/10.1016/j.jdermsci.2013.07.008.

Horn, Adam, and Jyoti K. Jaiswal. 2018. “Cellular Mechanisms and Signals That Coordinate Plasma Membrane Repair.” Cellular and Molecular Life Sciences, no. 0123456789. https://doi.org/10.1007/s00018-018-2888-7.

Jagannathan, N. Suhas, and Lisa Tucker-Kellogg. 2016. “Membrane Permeability during Pressure Ulcer Formation: A Computational Model of Dynamic Competition between Cytoskeletal Damage and Repair.” Journal of Biomechanics 49 (8): 1311–20. https://doi.org/10.1016/j.jbiomech.2015.12.022.

Jasiulionis, Miriam G. 2018. “Abnormal Epigenetic Regulation of Immune System during Aging.” Frontiers in Immunology 9 (FEB): 1–14. https://doi.org/10.3389/fimmu.2018.00197.

Karch, Jason, and Jeffery D. Molkentin. 2015. “Regulated Necrotic Cell Death: The Passive Aggressive Side of Bax and Bak.” Circulation Research 116 (11): 1800–1809. https://doi.org/10.1161/CIRCRESAHA.116.305421.

Levine, Jeffrey M. 2016. “Skin Failure: An Emerging Concept.” Journal of the American Medical Directors Association 17 (7): 666–69. https://doi.org/10.1016/j.jamda.2016.03.014.

Maslanik, Thomas, Lucas Mahaffey, Kate Tannura, Lida Beninson, Benjamin N. Greenwood, and Monika Fleshner. 2013. “The Inflammasome and Danger Associated Molecular Patterns (DAMPs) Are Implicated in Cytokine and Chemokine Responses Following Stressor Exposure.” Brain, Behavior, and Immunity 28: 54–62. https://doi.org/10.1016/j.bbi.2012.10.014.

Nanduri, Jayasri, Gregg L. Semenza, and Nanduri R. Prabhakar. 2017. “Epigenetic Changes by DNA Methylation in Chronic and Intermittent Hypoxia.” American Journal of Physiology-Lung Cellular and Molecular Physiology 313 (6): L1096–1100. https://doi.org/10.1152/ajplung.00325.2017.

Nyström, Alexander, and Leena Bruckner-Tuderman. 2018. “Injury- and Inflammation-Driven Skin Fibrosis: The Paradigm of Epidermolysis Bullosa.” Matrix Biology, no. 2017: 1–14. https://doi.org/10.1016/j.matbio.2018.01.016.

Pakos‐Zebrucka, Karolina, Izabela Koryga, Katarzyna Mnich, Mila Ljujic, Afshin Samali, and Adrienne M Gorman. 2016. “The Integrated Stress Response.” EMBO Reports 17 (10): 1374–95. https://doi.org/10.15252/embr.201642195.

Pandolfi, Franco, Simona Altamura, Simona Frosali, and Pio Conti. 2016. “Key Role of DAMP in Inflammation, Cancer, and Tissue Repair.” Clinical Therapeutics 38 (5): 1017–28. https://doi.org/10.1016/j.clinthera.2016.02.028.

Park, Sangbum, David G. Gonzalez, Boris Guirao, Jonathan D. Boucher, Katie Cockburn, Edward D. Marsh, Kailin R. Mesa, et al. 2017. “Tissue-Scale Coordination of Cellular Behaviour Promotes Epidermal Wound Repair in Live Mice.” Nature Cell Biology 19 (2): 155–63. https://doi.org/10.1038/ncb3472.

Pichu, Sivakamasundari, Selvaraj Vimalraj, Jayalalitha Sathiyamoorthy, and Vijay Viswanathan. 2018. “Association of Hypoxia Inducible Factor-1 Alpha Exon 12 Mutation in Diabetic Patients with and without Diabetic Foot Ulcer.” International Journal of Biological Macromolecules 119: 833–37. https://doi.org/10.1016/j.ijbiomac.2018.08.011.

Rathinam, Vijay A.K., and Francis Ka Ming Chan. 2018. “Inflammasome, Inflammation, and Tissue Homeostasis.” Trends in Molecular Medicine xx (3): 1–15. https://doi.org/10.1016/j.molmed.2018.01.004.

San Miguel-Ruiz, José E., and José E. García-Arrarás. 2007. “Common Cellular Events Occur during Wound Healing and Organ Regeneration in the Sea Cucumber Holothuria Glaberrima.” BMC Developmental Biology 7: 1–19. https://doi.org/10.1186/1471-213X-7-115.

Smit, Harm Jaap. 2018. “A Five-Level Model for Wound Analysis and Treatment.” Wounds UK 14 (4): 24–29. https://www.wounds-uk.com/journals/issue/548/article-details/five-level-model-wound-analysis-and-treatment.

Tang, Sindy K Y, and Wallace F Marshall. 2017. “Self-Repairing Cells: How Single Cells Heal Membrane Ruptures and Restore Lost Structures.” Science (New York, N.Y.) 356 (6342): 1022–25. https://doi.org/10.1126/science.aam6496.

Whyte, J. L., a. a. Smith, and J. a. Helms. 2012. “Wnt Signaling and Injury Repair.” Cold Spring Harbor Perspectives in Biology 4 (8): a008078–a008078. https://doi.org/10.1101/cshperspect.a008078.

Ps. It is really weird, writing a text like this when your name is … Harm.

 

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Level 0 Level 1 Level 2 Level 3 Level 4

Five levels, how to do it.

The original 5-level article was published in WoundsUK, you can find it here.

The five levels model provide you with a holistic checklist and allow you to map what is driving the events in any given wound.

Even though it is tempting to immediately jump in, that would lead to an almost incomprehensible list of factors to check. Perhaps it is easier to do it in an iterative way, where you have a very simple first pass and then, if you do not find a proper explanation for what is happening in the wound, you do further iterative passes. Depending on the findings of the previous pass(es), you zoom in and cast a finer net.

 

The basic idea behind a five-level wound analysis contains three ideas:

  1. You divide your problem into two new problems and keep doing that.
  2. Use the 5 levels as a checklist to see if you have missed something.
  3. If you do not find a solution,  redo 1 and 2 asking more questions and a larger checklist.

 

As any professional will know; wound healing is a complex field requiring knowledge, skills and tools on a variety of issues at all levels. The amount of knowledge, skills and tools needed increases at each round of questioning or pass.  Applying the 5-level system requires experience and a profound knowledge of tissue repair and regeneration. It requires understanding and ability to execute diagnostic tests. Finally, it requires knowledge of many comorbidities, lab values and medication.

The five levels are a result of 4 questions mapping your problem.

  1. Will this wound heal normal or not?
  2. If not will it heal by itself or will it not heal?
  3. If it will heal by itself, does it require advanced wound care or can it do without?
  4. If it will not heal by itself, is it because of organ system failure (usually vascular problems or repetitive damage) or because of cellular, molecular or genetic disorders?

By definition, any complex wound will have phenomena acting simultaneously on all levels. Having a full picture will provide a better understanding of the problems and possible remedies.

First pass, analysis

  • First question: will this wound heal normally, yes or no?
    • If yes, you have a level 0 wound. Take good care of the wound. It can be as simple as putting a bandage on; any bandage.
    • Chances it is a no, is when the wound exists for a longer period, your patient is over 65 years of age and/or has diabetic, dyslipidaemic, social, mobility, cardiovascular, neurological, immunologic or renal issues.
    • If no, the wound will heal not normally, leading to the
  • Second question: will this wound heal by itself or will this wound not heal by itself?
    • If yes, it is a level 1 or 2 wound. Consider minimal intervention, intervention means disruption of the normal life which can cause issues by itself.
    • A level 1 wound does not need special care.
    • Al level 2 wound requires wound care.
    • If no, the wound will not heal by itself, it is a level 3 or 4 wound, leading to.the
  • Third question: what is preventing the wound from healing?
    • Chances it is a wound resulting from arterial problems, venous problems or tissue damage due to repetitive forces. Figure out how grave the problem is and how to handle it.
    • Level 3 wounds require specialist care to solve the cause.
    • Level 4 wounds require specialist care. Currently, most level 4 diagnostic tools and interventions are in a research stage.
    • If needed appropriate, consider referring to a specialist able to solve or reduce the problem. It can be a specialised nurse, dermatologist, vascular surgeon, internal doctor or a podiatrist. Optimally all of them combined in a specialised wound care construction (not necessarily at one location).

 

First pass, checklist.

  • Check all 5 levels for issues which cause the wound or which may be not a direct cause for the wound but influence its trajectory. They are listed in the article.

 

First pass; act.

Select and apply your interventions.  Less is more.

 

First pass; review.

  • If the wound improves, redo the first pass for any changes or signals the wound might not improve on the next visit.
  • If the wound does not improve it is time for the second pass.
  • The goal of the second pass is to redo the first pass:
    • double check your assumptions.
    • have a closer look at the factors influencing the wound trajectory.

Having a closer look at the factors influencing the wound is important because, for instance, an infection can have a dramatic effect on the wound healing. But there are many more factors worth investigating. Causal and correlating factors have to be considered simultaneously. Most correlating factors are found on level 1. On the other levels, both causing and correlating factors can be found.

 

 

 

Second pass; analysis.

  • Is the cause well defined?
    • If yes, focus in the second pass on factors related to the cause. You can use the concise checklist for generating ideas.
  • Check level 1 for any causal or correlating factors which may point to problems on level 2, 3 and 4.
    • Consider other or more precise tests.
    • Identify possible tests and issues
  • Check level 2 for any causal or correlating factors which may point to problems on level 3 and 4.
    • Consider other or more precise tests.
    • Identify possible tests and issues, debride the wound thoroughly.
  • Check level 3 for any causal or correlating factors which may point to problems on level 3 and 4.
    • Consider other or more precise tests.
    • Identify possible tests and issues
  • Check level 4 for any causal or correlating factors which may point to problems on level 1, 2, 3 and 4.
    • Consider other or more precise tests. This includes a closer look at lab values.
    • Identify possible tests and issues.

 

  • Consider all issues and tests, look for connections which help explain what is going on.
    • Decide which test may improve your understanding or underpin possible interventions
    • Decide which intervention(s) will have the most impact on the wound trajectory.

 

Second pass; act.

  • Select and apply your tests and interventions, consider referring the patient.

 

Second pass, review

  • See if the wound has improved as a result of your interventions
  • If the wound improves, redo the first pass for any changes or signals the wound might not improve on the next visit.
  • If the wound does not improve, do a third pass by redoing the second pass.

 

Third pass

  • Is the cause well defined?
  • If yes, focus in the third pass on factors related to the cause.
  • But also consider marginal interventions, not aimed at resolving the cause but at improving the body’s ability to maintain, repair or regenerate tissue.
  • Check for patterns in issues, factors can be related or even appear in an interrelated fashion.
  • Try to learn from the previous pass(es).
  • Try to improve your knowledge, skills and tools by seeking options for discussion and learning.

 

Conclusion

It will be clear that even answering question one seems simple enough, it is not, this judgement requires quite some experience. But progress in the wound after one or two weeks will tell you if the judgement was justified. After running the analysis you will have a better idea of what is happening in your patient and the wound. This will help you in finding better ways to intervene. You will also learn what the limitations are in terms of available knowledge, experience and tools. Some are unavailable to you, others do not exist.

Even though this simple way is focussing on existing wounds, the insights resulting from it can also be used to predict and prevent wounds. Especially because harm may well exist prior to the formation of a wound or lesion, it is detectable and treatable.

Harm Smit

 

If you have any questions, do not hesitate to ask.

 

 

 

 

 

 

Categorieën
Level 4

Force Related Tissue Damage: A White Paper

Damage to skin and tissue is an important and expensive issue for the NHS and other organisations providing care for those who are confined to their bed or chair for any period of time. The costs are not just financial; a lot of individual suffering and loss of quality of life occur when tissue breaks down. This white paper brings together existing research into skin and tissue damage associated with patient’s being cared for in bed.
The latest term being used for this is pressure injury (NPUAP 2016). This term replaces previous terminology used such as; pressure ulcers, pressure sores, bed sores /ulcers and decubitus ulcers. However, with our extensive review of the literature into the internal and external influences, we believe a more accurate description is force related tissue damage.
This paper investigates the observations regarding unobvious causes of force related tissue damage and the events linking both biomechanical and biological processes at several organisational (pathological) levels together with external in bed events. Over 22 internal marginal influences are identified which, as countless Cochrane reviews demonstrate, wound care science struggles to diagnose and cure; mostly due to the underestimation of the complexity and processes involved regarding tissue homoeostasis, damage and regeneration.
The paper explains how there are two major causal factors connected with all in bed force related tissue damage. The patient’s resting/support surface synergy and the way the person is moving/being moved and stabilised on that surface, regardless of whether this is by manual or mechanical means. We will explore how in bed force related tissue damage can be a direct result of both manual and/or mechanical handling and the incorrect synergetic interface layers of the resting/support surface with the patient’s skin and tissues.
We strongly suggest the major causal factors involved with all in bed force related tissue damage are external and within our control. This paper proposes that a preventative trajectory is both desirable and achievable by adopting a combined ergonomic and biomechanical approach to remove the risks to both patients’ skin/tissue and the carer’s muscular-skeletal system associated with in bed care and positioning.
Harm Smit and Phil Strong 2018

 

Here is the link to the paper: White Paper Force related tissue damage

Categorieën
General

Morgen weer een training

Morgen mag ik weer een training voor de Buurtzorg verpleegkundigen verzorgen. Mijn taak is om ze in te leiden in de biologie van de wondgeneeskunde. Het is een enorme uitdaging om in een paar uur (gelukkig is die tijd er) niet alleen uit te leggen wat er gebeurt (4 fasen) maar ook hoe en waarom het gaat zoals het gaat. Gelukkig kan dat ook zonder al te veel wis-, natuur- en scheikunde. Maar dan nog is het veel en ingewikkeld.

Met een bredere wetenschappelijke inleiding krijgen ze een inkijkje in wat er werkelijk gebeurt in een complexe wond en kunnen ze uitleggen (en berekenen) waarom de de effecten van bijvoorbeeld topicale wondbehandeling niet of zelden aantoonbaar zijn in de praktijk (de schijnbare Cochrane vs Winter paradox). Dat leert je meteen ook wat je wel kunt doen en erger nog, wat je zou willen doen maar wat niet kan.

Ik hoop dat ze begrijpen hoe ze de effectiviteit van hun handelen kunnen verbeteren, al was het maar om de effectiviteit van “vochtig behandelen” en andere interventies te verhogen.

Het is een inleiding, het is basale wetenschap van de wondgenezing, ik kan in een halve dag niet iemand van “verbandplakker”(en dat deze studenten zeker niet, heb ik gemerkt) tot “wondbehandelaar” transformeren. Het is lastige stof en een andere manier van denken. Dat is tijdens de training nog te volgen maar ik weet dat het daarna lastig wordt. Ingewikkelde zaken zo uitleggen dat men het snapt en onthoudt is lastig maar ik probeer het wel, met vallen en opstaan, omdat ik denk dat het nodig is.

 

Harm jaap

P.s. laat nog even weten wat volgens jou een verpleegkundige, medicus, paramedicus of een andere professional zou moeten kunnen en weten om wonden te mogen behandelen.

Categorieën
General

Jaarlijks 18.000 dodelijke decubitus slachtoffers in Nederland?

In een BBC bericht staat dit: “Pressure sores kill 60,000 people a year and cost the NHS £2.1bn annually.” Als we dit naar Nederland vertalen, het Verenigd Koninkrijk heeft 55 miljoen inwoners en Nederland heeft er 17 miljoen.  (ongeveer 0,3x Engeland.) Dat zou betekenen dat er in Nederland 18.000 personen per jaar overlijden aan decubitus wonden. Waarbij de kosten dan op ongeveer 700 miljoen euro op jaarbasis uitkomen.

Ik denk dat de kosten wel kloppen. Het CAPgemini rapport (Capgemini Consulting, Innovatie van complexe wondzorg.  2014) komt zelfs veel hoger uit.

Het aantal slachtoffers klopt denk ik niet, dat zal (veel) lager liggen. (Al was het maar omdat ik dat altijd aan professionals vraag)

Zo’n bericht roept wel vragen op. Om te beginnen is het onduidelijk waar het getal vandaan komt. Als het uit het hoofd van een overijverige medewerker van het bedrijf komt (wat niet onmogelijk is) snap ik niet waarom professor Moore en de BBC er in mee gaan. Maar waar rook is, is vuur en als het getal wel “hard” is hebben we hier een probleem.

Maar dat is niet het echte probleem.

Het echte probleem is dat een wond als doodsoorzaak bijna niet te vinden is in de Nederlandse statistiek. ( Capgemini Consulting, Innovatie van complexe wondzorg.  2014)

We zijn in Nederland blijkbaar van mening dat je aan wonden niet doodgaat. (Anders had er wel ergens een getal in de statistiek gestaan).

Maar als in het Verenigd Koninkrijk 60.000 decubitus doden worden geteld, waarom tellen we er in Nederland dan 0? Het zijn er trouwens geen nul, ik sprak laatst ook nog iemand die ervan overtuigt was dat er in Nederland niemand aan decubitus overlijdt. Dat wil zeggen, tot een overstap naar een andere instelling. Toen is de overtuiging 180 graden gedraaid. Dus ja, ook in Nederland overlijden mensen aan decubitus en ja er is kwaliteitsverschil.

Maar hoeveel weten we dus niet. En het lijkt erop dat we het ook niet willen weten (lees; een wond is een complicatie en geen indicatie), want als er ineens 18.000 of 1.800 doden blijken te zijn kun je niet op je handen blijven zitten. En dat geeft gedoe.

Behalve cijfermatig is ook onze kennis en kunde van chronische wonden onder de maat waardoor bijvoorbeeld CZ genoodzaakt wordt om op waarde (goedkope verbandjes en onderbetaalde thuiszorg) in plaats van kwaliteit (minder wonden) wondzorg in te kopen. (zie p7 Waardegedreven zorginkoop bij complexe wonden) .

Toch jammer, dat je op waarde moet inkopen terwijl de echte besparingen op kwaliteit te halen zijn. Ik neem aan dat ze daar bij CZ ook niet trots op zijn.

Conclusie:

Een wond wordt in Nederland niet als een probleem gezien. Ook niet als het jaarlijks honderden miljoenen kost en in Engeland blijkbaar tienduizenden slachtoffers eist.

We vinden het wel best zo…

Harm Jaap

 

Ref:

 

Bij vragen kun je gewoon mailen  (harmjsmit-at-gmail.com) of bellen (0645444310)

 

Categorieën
Level 1

Waarom je wonddiagnose begint met de postcode.

Dit is een level 1 dingetje.

Zoals elke dag, komt er iemand je poli op met een wond. Dan moet je vaststellen wat er aan de hand is. Dat betekent dat je mag nagaan wat voor wond het is en wat je behandelmogelijkheden zijn. Gek genoeg bepalen de behandelmogelijkheden in hoeverre je behandeling kans van slagen heeft.

Is de wond überhaupt wel te behandelen?

De reden dat de patiënt naar jou toekomt betekent dat iemand anders denkt dat hij of zij niet de optimale behandeling kan bieden. Het kan zijn dat de diagnose niet klopt. Dit zou in Nederland niet te vaak mogen gebeuren maar helaas is de praktijk nog te vaak anders.

De tweede reden is dat de behandeling niet aanslaat. Waarom slaat de behandeling niet aan?

In Nederland bestaat de initiële behandeling uit het toepassen van een wond / compressie verband. Dat zou in 90% van de gevallen afdoende moeten zijn. Toch gaat de wond, vaker dan zou mogen, niet dicht. Dus als de “normale behandeling”  niet werkt is er iets bijzonders aan de hand. Meer dan je zou verwachten heeft dat te maken met het opvolgen van de adviezen van de professional door de patiënt.

Trekt u goede schoenen aan, beweegt u voldoende, verwisselt u het verband op tijd, slaapt u goed genoeg, eet u goed wel goed, belt u als het niet lukt?

Daar wringt vaak de schoen. Ondanks alle goede bedoelingen lukt het de patiënt niet om de adviezen op de volgen.

Nu wordt het interessant.

Uit recent obesitas onderzoek blijken de te dikke kinderen vaak bij elkaar in de wijk wonen. Het is zelfs zo dat de wijk belangrijker voor het ontstaan van overgewicht is de andere factoren! Niet alleen voor obesitas is dat zo, ook voor diabetes. Dus als iemand te dik is of diabetes heeft kan de omgeving waar je woont een hele belangrijke oorzaak zijn van het ontstaan en in stand houden van obesitas of non-compliance. Helaas zijn dat vaak de achterstandswijken.

Dat betekent dus dat de omgeving veel belangrijker is dan we dachten. Het wordt nu wel heel oneerlijk om tegen iemand te zeggen dat adviezen niet opvolgen, te dik of ziek zijn een keuze is. Dat is hetzelfde als zeggen dat arm zijn een bewuste keuze is. Soms is het niet anders.

Dat geldt dus ook voor jouw patiënt. Doen wat de verpleegkundige of dokter vraagt lijkt een keuze van de patiënt maar is dat dus niet altijd.

Dat betekent dat de postcode heel bepalend kan zijn in wat je van iemand kunt verwachten. En bovendien op een manier die je niet verwacht.

Dat het voor jou makkelijk is om goede schoenen te dragen, voldoende te bewegen en al die andere zaken te doen om de genezing te bespoedigen is geen enkele reden om aan te nemen dat dat voor jouw patiënt ook maar in de buurt komt van een keuze. Compliance, of het gebrek daaraan is, dus veel vaker dan je dacht, geen keuze maar een feit.

Daarmee geeft de postcode een belangrijke aanwijzing over de mogelijkheden tot compliance. Vaak bepaald compliance je behandelmogelijkheden, soms meer dan de wond.

Uiteraard is dit maar één aspect van alle zaken waar je mee te maken hebt. Het maakt wel duidelijk dat een, op het eerste gezicht logische, redenatie wel eens niet kan kloppen. Iets om rekening mee te houden.

Zo zijn er nog een paar zaken om rekening mee te houden in een (level 1) diagnose.

 

Referenties:

https://www.ncbi.nlm.nih.gov/pubmed/28164370

https://www.ncbi.nlm.nih.gov/pubmed/28445431

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2789291/

https://www.ncbi.nlm.nih.gov/pubmed/28510620

https://www.ncbi.nlm.nih.gov/pubmed/27319322

Categorieën
Level 4

4 ways a cell may die

For ninety five out of hundred wounds, discovering and removing the cause is sufficient to solve the problem. If that approach fails, the wound may become a chronic wound. For adequate interventions, (in this case super-) simplified knowledge of processes at cellular level may help. At least, in presentations it is appreciated.

Understanding how cells cope with stress, injury and damage is central in understanding the development and healing of wounds. There is no abrupt transition from normal tissue to necrotic tissue, in most wounds the conditions for cells are gradually getting worse towards the lesion, This is divided into a healthy part, a part in stress, a part with repairable damage and a part with non-repairable damage. This zone classification is different for each tissue type involved which may on of the explanations of tissue undermining, this happens when the underlying tissue is more susceptible to stress and damage comparted to the tissue above.

Cell stress and damage are often caused by the action of forces on tissue (1), lack of oxygen (2) and/or lack of nutrients (3). Stress and damage may lead to cell death, however, the most common cause of cell death is apoptosis, programmed cell death(4).

The action of forces on cells leads to pressure, tensile- and shear-forces. Increased pressure may cause membrane leakage, tensile forces can lead to cell rupture and shear forces can do both. Casual observance may suggest that pressures are the main cause of problems, but that is probably not the case. Cells and tissues are often anisotropic, which means they are not equally strong in all directions. Many tissues have a special construction to handle forces in a certain direction. If force is applied from a “wrong” direction to a cell or tissue it may deform or lose its tensegrity and tear. In addition, instead of popping and rupturing, deformation may most of the time be causing damage of the cell membrane resulting in calcium ions leaking into the cell which is a direct cause for problems.[1,2].

The cell nucleus senses the properties of force applied to the cell [3], this allows her to assess the situation and respond appropriately at the cellular level. Signalling and tensegrity systems augment and translate these signals to the higher organisational levels of tissue, organs and the body.

The availability of oxygen may also cause problems; human cells depend on haemoglobin for their oxygen supply. If a human cell has no access to oxygen produced by red blood cells it will die. Oxygen related issues usually cause mitochondrial problems. Under hypoxia. Mitochondrion will adapt its processes to keep producing energy, this process also produces reactive oxygen species and nitric oxides. These reactive substances signal the cell and its surroundings about the (oxidative) stress. Too many reactive parts are damaging so if the amount of reactive oxygen surpasses a threshold the immune system will be activated to remove damaged cells. This system allows tissue to function under hypoxic circumstances[4].

Lack of nutrients will disturb the cell metabolism, which will endanger its survival. Focal in these processes is the endoplasmic reticulum, which is sensitive to intracellular circumstances. Since the endoplasmic reticulum functions as the main chemical factory of cell producing most proteins any disturbance of the necrotic reticulum will have a dramatic effect. This is called endoplasmic reticulum stress (ER-stress)[5].

Circumstances such as exerted forces, hypoxia or a lack of nutrients are noted by the cell and it will respond to counter these problems(stress responses). However, these responses influence the internal cooperation between the nucleus, mitochondrion and the endoplasmic reticulum in positive or negative manner[2]. It is important for cells to not only adapt the internal processes but also to inform its surrounding about its problems. Therefore it will start sending out signals which quite specific inform surrounding cells and tissues and the rest of the body on the nature of its problems[6,7].

Cells are part of tissue, to maintain the quality of these tissues cells which are not functioning properly have to be removed or replaced. Removing non-functional or obsolete cells by the body itself is the commonest reason for cells to die. The body prefers to remove cells in a controlled manner where cells are properly recycled. This process is called apoptosis. The opposite process necrosis were cells structural fall apart and their contents are spread in the tissue. The remains of cells in tissue are the result of an uncontrolled situation and therefore have a strong signalling function, these are the so-called damps en pamps (damage-associated molecular patterns en pathogen-associated molecular patterns)[8].

Both apoptosis and necrosis exist in several varieties[9].

Cells do not immediately fall apart or die if exposed to forces, hypoxia or lack of nutrients. For practical reasons, we may classify the level of stress in stress (no damage, fully reversible), injury (reversible damage) and damage (irreversible damage). Stress does not require regeneration, injured tissue can regenerate fully, but damaged tissue cannot be regenerated fully and the body will try to restore the main functions of the tissue. This means that the affected area is much larger than the wound itself, this implies that visually vital tissue does not have to be vital that all.

Cells and tissues can adapt to survive difficult circumstances. Continuous monitoring the circumstances and the signals cells and tissues send out allow the body to respond. This can be a short-term responses where a blood vessel is opened up or an immune response is started. Long-term responses can be by changing the composition of tissues, for example making extra blood vessels to composite for lack of perfusion or changing collagen composition in support of tissue due to forces from different angles.

Regardless of the cause of the wound, the wound bed will, due to lack of perfusion, always, always suffer from odd forces and a lack of oxygen and nutrients. Due to the damage the structures the body uses to monitor the situation in the body like sensors, vessels and nerves are also dysfunctioning. This is a perfectly normal situation and most of the disturbance is actually used to guide the wound healing process. That is in a young patient, if the wound is larger, complex and or the patient has more issues related to tissue regeneration, this perfect process is impaired.[10,11].

This impairment be qualitative, wrong signals are send or misinterpreted. It can also be qualitative, more damage leads to more signals, more signals are harder to interpret and the signal to noise ratio is also reduced. Noise and miscommunication in the body, may lead to misinterpretation of signals or the generation of wrong signals. This may seem far-fetched, in practice it is called a chronic, wound.

An out-of-control inflammation response may cause havoc in a wound bed. This may produce additional damps which only increase the (sterile) inflammation[12]. And impaired endothelial hypoxia and capillary refill a cause reperfusion injury[13,14]. Reperfusion injury is a cause of problems in other parts of the body, like the lungs[15]. A cacophony of signals in the wound bed may disable guidance for cells which may cause impaired cell movements and proliferation. These are just a few of the many causes of chronic.

Despite the difference in causes, chronic wound pathology has surprising similarities at the level (4) of the cell and the tissue. And this opens up treatment possibilities. Not only are the issues often similar, there are several possibilities to intervene and restore impaired processes. Goal will be to either guide communication or delay the stress-injury-damage cascade. Available knowledge is not always available in the wound care practice. An example is the use of pentoxifylline, which is well documented for years [16–20] yet rarely used. There are dozens of other interventions like pentoxifylline available. Not only on this level, but also on the other four levels in wound knowledge a smorgasbord of interventions is available. So the real problem is not even new knowledge but to make current knowledge available for the clinical practice.

 

Literatuur:

1         Carafoli E, Krebs J. Why calcium? How calcium became the best communicator. J Biol Chem 2016;291:20849–57. doi:10.1074/jbc.R116.735894

2         Hill S, Van Remmen H. Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging. Redox Biol 2014;2:936–44. doi:10.1016/j.redox.2014.07.005

3         Belaadi N, Aureille J, Guilluy C. Under Pressure: Mechanical Stress Management in the Nucleus. Cells 2016;5:27. doi:10.3390/cells5020027

4         Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014;24:R453–62. doi:10.1016/j.cub.2014.03.034

5         van Vliet AR, Agostinis P. When under pressure, get closer: PERKing up membrane contact sites during ER stress. Biochem Soc Trans 2016;44:499–504. doi:10.1042/BST20150272

6         Krebs J, Agellon LB, Michalak M. Ca2+ homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling. Biochem Biophys Res Commun 2015;460:114–21. doi:10.1016/j.bbrc.2015.02.004

7         Elks PM, Renshaw S a, Meijer AH, et al. Exploring the HIFs, buts and maybes of hypoxia signalling in disease: lessons from zebrafish models. Dis Model Mech 2015;8:1349–60. doi:10.1242/dmm.021865

8         Herwald H, Egesten A. On PAMPs and DAMPs. J Innate Immun 2016;8:427–8. doi:10.1159/000448437

9         Nikoletopoulou V, Markaki M, Palikaras K, et al. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta – Mol Cell Res 2013;1833:3448–59. doi:10.1016/j.bbamcr.2013.06.001

10       van Beek JHGM, Kirkwood TBL, Bassingthwaighte JB. Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance. Interface Focus 2016;6:20150079. doi:10.1098/rsfs.2015.0079

11       Yin F, Sancheti H, Liu Z, et al. Mitochondrial function in ageing: coordination with signalling and transcriptional pathways. J Physiol 2015;0:n/a-n/a. doi:10.1113/JP270541

12       Feldman N, Rotter-Maskowitz A, Okun E. DAMPs as mediators of sterile inflammation in aging-related pathologies. Ageing Res Rev 2015;24:29–39. doi:10.1016/j.arr.2015.01.003

13       Manson PN, Anthenelli RM, Im MJ, et al. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg 1983;198:87–90. doi:10.1097/00000658-198307000-00017

14       Lejay A, Meyer A, Schlagowski AI, et al. Mitochondria: Mitochondrial participation in ischemia-reperfusion injury in skeletal muscle. Int J Biochem Cell Biol 2014;50:101–5. doi:10.1016/j.biocel.2014.02.013

15       Mansour Z, Charles AL, Kindo M, et al. Remote effects of lower limb ischemia-reperfusion: Impaired lung, unchanged liver, and stimulated kidney oxidative capacities. Biomed Res Int 2014;2014. doi:10.1155/2014/392390

16       Sharma K, Ishaq M, Sharma G, et al. Pentoxifylline triggers autophagy via ER stress response that interferes with Pentoxifylline induced apoptosis in human melanoma cells. Biochem Pharmacol 2016;103:17–28. doi:10.1016/j.bcp.2015.12.018

17       Sharma R, Randhawa PK, Singh N, et al. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms. Eur J Pharmacol 2015;768:58–70. doi:10.1016/j.ejphar.2015.10.029

18       Jull A, Waters J, Arroll B. Pentoxifylline for treatment of venous leg ulcers: a systematic review. Lancet 2002;359:1550–4. doi:10.1016/S0140-6736(02)08513-6

19       Jull AB, Arroll B, Parag V, et al. Pentoxifylline for treating venous leg ulcers ( Review ). Cochrane database Syst Rev 2012;12:CD001733. doi:10.1002/14651858.CD001733.pub3

20       Falanga V, Fujitani RM, Diaz C, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Wound Repair Regen 1999;7:208–13.

Categorieën
Level 0 Level 1 Level 2 Level 3 Level 4

An open letter to the Presidents of NPUAP and EPUAP

Open letter to the Presidents of NPUAP and EPUAP

(https://www.linkedin.com/pulse/open-letter-presidents-npuap-epuap-phil-strong )

Dear Madam Presidents,

We have been engaged and working within the ‘inbed’ * patient care sector for over 20 years; as health and social care practitioners, researchers and product developers. Today, we are deeply concerned that the NPUAP changes in ‘pressure injury’ terminology and ‘pressure ulcer’ classifications do not reflect the underlying causes of skin and tissue damage and that there has been selective use of the research from which the review was initiated.

We call on EPUAP during its review of the terminology and classifications to consider the views below and we suggest both NPUAP and its Staging Task Force to consider – in the light of the points below – whether their process really did produce the best outcome.

The pressure ulcer staging consensus is a further development of the original guidelines published in 1975. The updating processes in is described in the your first reference [1].  The procedure was divided in two parts, statements from which are backed by research and are a result of the consensus processes. However, it is not clear on what ground decisions were referred to either research or consensus. For example:

  • Do not use DTPI to describe vascular, traumatic, neuropathic, or dermatologic conditions

This is in conflict with the research findings where vascular disease is a causing factor of deep tissue injury[2–6].

  • The statement from the first reference in the document: “The staging system for pressure injury of the skin cannot be used to stage mucosal membrane pressure injury”.

In what way are mucosal membranes so different anatomically that not one of the proposed seven stages is applicable?

  • The literature selection process: “The CINAHL and MEDLINE electronic databases were searched individually; this search yielded 3652 articles. Task Force members completed title and abstract reviews, along with full text review. Two hundred forty-two articles were deemed relevant to the task at hand. In addition, references submitted by stakeholders and the public during the comment period were retrieved and reviewed for relevance to the goals of the Task Force.”

This statement Is biased due to the addition of stakeholder references for two reasons. Firstly, adding extra articles by stakeholders implies the original algorithm is sub optimal. Secondly, hand picking articles is biased by definition; especially since they added to the original 242 articles.

  • It appears the consulted professional and government or regulatory organisations are primarily nursing-based organisations rather than a balanced sample of stakeholders.

Position Statement 1: The diagnosis of a “pressure injury” does not mean that the health care provider(s) “caused” the injury.

Tissue damage associated with patients being cared for ‘inbed’ have been historically called pressure ulcers, pressure sores, bed sores/ulcers, decubitus ulcers and other names. The latest term being used is pressure injury. Since the word pressure is used to describe pressure, shear and tension depending on the direction of the forces involved, a more accurate description is ‘force-related tissue damage’ and so we will be using this term throughout this response.

The fact that an entire paragraph is dedicated to the word “injury”, indicates that the NPUAP foresees legal problems in the words used.

For example, anticipatory design of both products and practices must be used to enable tissue damage prevention when moving and stabilising a patient being cared for ‘inbed’ by:

  • creating the correct resting-surface/patient synergetic support layers
  • requiring the products/practices to work with gravity, rather than against it.
  • preventing tissue strain in static and moving situations

Position Statement 2: Some pressure injuries are unavoidable despite provision of evidence based care by the health care team.

The second position statement is on the avoid-ability of force-related tissue damage. However, NPUAP fails to provide qualitative or quantitative data on the number of an unavoidable force related injuries.

  • Whilst the references speak of unavoidable “pressure sores”, they do so in relation to the availability of high-quality care. This qualitative approach indicates a larger chance of developing an “unavoidable “ulcer yet no quantitative evidence is provided to substantiate this.
  • However well-intentioned the currently accepted and evidence-based ‘inbed’ care practices and products are, patients are still suffering. Some patients are more prone and of a higher risk to tissue damage (for example due to spinal cord injury or are of older age). However, there are those patients who don’t fit into these categories that are also prone and are at risk to tissue damage when the body’s threshold of resistance and/or ability to recover from damage, is exceeded.
  • The real issue of this statement is a cost-benefit analysis and indicates that the number of so-called unavoidable ulcers can be reduced even further with the use of advanced medical and nursing techniques. A casual glance at related medical fields like cardiology, nephrology and brain research shows there are many readily available diagnostic techniques and interventions to prevent and/or resolve forced-induced injuries. However, this raises the question whether society is able or willing to carry the cost involved with avoiding “the last ulcer”.

The second part of paragraph 2 points the eventual plaintiff towards asking if the best available care has been applied. Available care would include current available standard medical procedures which are applicable for wound care. It would be fair to say that the non-availability of these tools would and should not be accepted as a reasonable argument by a judge in 2017. This raises the question why non-availability of basic medical procedures is acceptable for a health care provider or any other medical professional.

The best available care would indicate that all the ways external forces can compromise a patient’s ‘inbed’ tissue integrity have been avoided. These would include:

  • Avoiding any unnecessary external forces that can be generated by how the patient is rested, how they are moved and how they are re-stabilised, both during and after their body mass has been re-orientated.
  • Avoiding harmful forces generated as a result of both inconsistent manual handling practices and the use of mechanical means that are working against gravity and trying to overcome the gravitational pull forces that are keeping the patient stable.
  • That these external forces are controlled in a way that any patient movement and stabilisation works with rather than against gravity. Allowing the body to move and be re-orientated safely, further compliments and supports the body’s innate homeostasis to keep the patients skin and tissues within its natural threshold of resistance and repair. Thereby, maintaining its optimum tissue integrity.

NPUAP and EPUAP needs to recognise that new research is available to show that the best available care would also include managing the one major external factor in the patient’s environment in all ‘inbed’ tissue damage occurrences: the patient interfaces with a resting/support surface.

Position Statement 3: The numerical staging system does NOT imply linear progression of pressure injuries from Stage 1 through Stage 4, nor does it imply healing from Stage 4 through Stage 1.

The fact that the third position statement actually states that there is no logical connection between the stages in the consensus document is interesting because the four-stage wound healing process is exactly describing healing from stage 4 to stage 1 (Wikipedia).

By stating this, NPUAP appears to be concluding that each stage has its own specific aetiology and that underlying pathology may be a connection between the stages. We agree and challenge NPUAP and EPUAP that force related tissue injuries should therefore be staged/classified based on the underlying pathology.

Position Statement 4: The NPUAP Staging System classifies pressure injuries based on the type of tissue loss that can be visualized or directly palpated.

The fourth position statement is identifying the exact problem. The classification is based on type of tissue loss that can be visualised or directly palpated. Not only is the classification superficial, it also denies underlying pathology, for example, why is a mucosal force related injury unstageable?

Imagine what the clinical relevance a classification based on type of tissue that can be visualised directly palpated for any type of wound would be? It is immediately clear that this classification is descriptive but bears no relation to the aetiology or possible interventions and is therefore not clinically relevant. Categorising a wound as unstageable can, under circumstances, be considered evidence of neglect due to lack of debridement.

Classical diagnostic tools such medication (STOPP/START) screening [7,8], lab values[9,10], biomarkers[11,12], tissue sampling[13,14] and imaging[15,16] are not mentioned in the guidelines. Advanced diagnostic tools such as (epi) genetic[13,17–19], proteomic[20] and metabolomic[21,22] screening are also not mentioned.

Position Statement 5: The pressure injury may be more extensive than initially apparent. The wound base and surrounding tissue should be assessed for variations in sensation, temperature, firmness, color and any expression of drainage from surrounding tissues when palpated.

Position statement five is claiming that there is more than meets the eye. However, these findings are to be noted but are neither qualified, quantified or part of the staging process. This is a very true statement. There are at least 22 internal factors that can contribute to the loss of optimum tissue integrity i.e. that can cause/contribute to both a reduction in the tissue resistance threshold and/or a reduction in tissue recovery. These include generic factors (such as stress), systematic factors, structural factors and local factors.

It would be better therefore, if statement 5 would be reframed to diagnosis of pre-clinical events leading to stress, injury and damage at a molecular, cellular, tissue organ and organism level. That would be a nice starting point for bringing wound care to this century.

Position Statement 6: Deep Tissue Pressure Injury (DTPI) may evolve into a full thickness wound despite optimal care.

Position statement six is actually the same as position statement five. In court, however, this would make a difference. Interesting statements such as NPUAP’s “Off-loading the area still offers the best chance for tissue that is ischemic or injured, but not infarcted” is in conflict with medical ethics where chance should be avoided at all times. You may consider: “diagnostic tools for assessing and grading DTI, endothelial status and reperfusion injury are being investigated”.

Position Statement 7: Any pressure injury should be treated in accordance with current evidence-based practices and monitored closely for changes that require re-evaluation of treatment strategies.

Position statement seven is correct. However, guidelines do not allow proper execution of the statement. Close monitoring for changes that require re-evaluation of treatment strategies based on the six stages is dangerous and ethically questionable. NPUAP appears to realise this because they provide examples of deep tissue injury developing into a stage IV injury. However, having to explain this implies that the current guidelines are not sufficient for prescribing and handling the events related to force related injuries.

However, we challenge NPUAP and EPUAP to promote that force-related tissue damage prediction and  prevention rather than treatment is always the preferred approach to maintaining optimum tissue integrity. Evidence-based care should be demonstrating that

  • The patient’s ‘inbed’ environment provides the optimal synergetic resting support surface layers including the bed frame, bed mattress, bed mattress cover, sheets, any incontinence slide, the patient’s clothing, the patient’s skin and tissue
  • That external forces are controlled in a way that any patient movement and stabilisation works with rather than against gravity to maintain optimum tissue integrity. i.e. allows the body to move and be re-orientated safely, by allowing the body’s innate homeostasis to keep the patients skin and tissues within its natural threshold of resistance and repair.
  • The care provided allows the body to protects and repairs its internal environment by using both physiological and biomechanical mechanisms (tensegrity) and homoeostasis to maintain optimum tissue integrity.

Conclusion

The NPUAP document on current staging of pressure related injuries is superficial and does not make use of current available knowledge and techniques. It does not measure up to modern standards of care.  The fact that the methodology used is entirely ignoring underlying pathology in a way that it would be criminal to use pressure injury staging methodology on, for instance, a leg ulcer.

The claim that,” The NPUAP has provided the gold standard for diagnosis and classification of pressure injuries for nearly three decades, and counting.” Is therefore not entirely correct.

The document focuses solely on treatment rather than prevention:

  • It does not address the gap of what should be and what is available for both the caregiver and the care receiver.
  • It does not promote the best-practice for designing out unsafe practice (higher-level hierarchy risk control),
  • It does not eliminate the use of unsuitable products
  • It continues to rely on monitoring compliance
  • It overlooks the designing-in prevention and a safer care trajectory

By taking this safer, combined ergonomic and biomechanical approach, NPUAP and EPUAP can make a real difference to the occurrence of force-related tissue damage and remove the risks to both carers and patients associated with ‘inbed’ care and positioning.

NPUAP and EPUAP need to promote the evaluation and use of technology to fill in the gaps for inconsistencies in patient care and should give the patient and carer what they need:

  • Patients need a safe environment (social or hospital) to enhance their care.
  • Whilst being cared for ‘inbed’, they need to avoid tissue damage.
  • They require effective infection control that prevents them contracting other infections whilst receiving their care.
  • They need to be at an optimum temperature.
  • Nurses and carers need products that are intuitive and easy to use, and are compliant with safe patient care expectations and regulation.

Signed:

Phil Strong SRN RNMS Cert. Ed CT NT, Managing Director & Product Designer, Ergo-Ike Ltd, Associate Member of the CIEHF

Harm J Smit MSc, Wound Care Biologist, BioMedServ

*    By “inbed” we mean: any resting /support surface facility which enables the patient to receive care, support and movement. This can include for example: beds (domestic/clinical), theatre tables, theatre trolleys, gurneys and X-ray tables, chairs and wheelchairs. Although this list is not exhaustive.

References

http://www.npuap.org/wp-content/uploads/2012/01/NPUAP-Position-Statement-on-Staging-Jan-2017.pdf

1           Edsberg LE, Black JM, Goldberg M, et al. Revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System: Revised Pressure Injury Staging System. J wound, ostomy, Cont Nurs Off Publ Wound, Ostomy Cont Nurses Soc2016;43:585–97. doi:10.1097/WON.0000000000000281

2           Farid KJ. Applying observations from forensic science to understanding the development of pressure ulcers. Ostomy Wound Manage 2007;53:26–8, 30, 32 passim.http://www.ncbi.nlm.nih.gov/pubmed/17449915

3           Mekkes JR, Pasch MC, Meijs M, et al. Acquired arteriovenous malformation induced by pressure: a case report. Vasc Med 2003;8:201–2. doi:10.1191/1358863x03vm497cr

4           Nagel T, Loerakker S, Oomens CWJ. A theoretical model to study the effects of cellular stiffening on the damage evolution in deep tissue injury. Comput Methods Biomech Biomed Engin 2009;12:585–97. doi:10.1080/10255840902788603

5           Loerakker S, Solis LR, Bader DL, et al. How does muscle stiffness affect the internal deformations within the soft tissue layers of the buttocks under constant loading? Comput Methods Biomech Biomed Engin 2013;16:520–9. doi:10.1080/10255842.2011.627682

6           Solis LR, Liggins AB, Seres P, et al. Distribution of internal strains around bony prominences in pigs. Ann Biomed Eng 2012;40:1721–39. doi:10.1007/s10439-012-0539-y

7           Hill-Taylor B, Walsh KA, Stewart S, et al. Effectiveness of the STOPP/START (Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment) criteria: Systematic review and meta-analysis of randomized controlled studies. J Clin Pharm Ther 2016;41:158–69. doi:10.1111/jcpt.12372

8           Levine JM. The Effect of Oral Medication on Wound Healing. Adv Skin Wound Care 2017;30:137–42. doi:10.1097/01.ASW.0000512112.60254.28

9           Gould LJ, Olney CM, Nichols JS, et al. Spinal Cord Injury survey to determine pressure ulcer vulnerability in the outpatient population. Med Hypotheses2014;83:552–8. doi:10.1016/j.mehy.2014.08.027

10         Callahan D, Keeley J, Alipour H, et al. Predictors of Severity in Diabetic Foot Infections. Ann Vasc Surg Published Online First: 2015. doi:10.1016/j.avsg.2016.01.003

11         Lindley LE, Stojadinovic O, Pastar I, et al. Biology and Biomarkers for Wound Healing. Plast Reconstr Surg 2016;138:18S–28S. doi:10.1097/PRS.0000000000002682

12         Tegl G, Schiffer D, Sigl E, et al. Biomarkers for infection: enzymes, microbes, and metabolites. Appl Microbiol Biotechnol 2015;99:4595–614. doi:10.1007/s00253-015-6637-7

13         Januszyk M, Gurtner GC. High-Throughput Single-Cell Analysis for Wound Healing Applications. Adv wound care 2013;2:457–69. doi:10.1089/wound.2012.0395

14         Voegeli D, Lwaleed B. Back to basics: histological, microbiological and biochemical sampling in wound care. J Wound Care 2013;22:650–2, 654. doi:10.12968/jowc.2013.22.11.650

15         Stekelenburg A, Strijkers GJ, Parusel H, et al. Role of ischemia and deformation in the onset of compression-induced deep tissue injury: MRI-based studies in a rat model. J Appl Physiol 2007;102:2002–11. doi:10.1152/japplphysiol.01115.2006

16         Linder-Ganz E, Gefen A. Stress analyses coupled with damage laws to determine biomechanical risk factors for deep tissue injury during sitting. J Biomech Eng 2009;131:11003. doi:10.1115/1.3005195

17         Anderson AE, Galko MJ. Rapid clearance of epigenetic protein reporters from wound edge cells in Drosophila larvae does not depend on the JNK or PDGFR/VEGFR signaling pathways. Regeneration 2014;1:11–25. doi:10.1002/reg2.12

18         Zhang S, Duan E. Epigenetic regulations on skin wound healing: implications from current researches. Ann Transl Med 2015;3:227. doi:10.3978/j.issn.2305-5839.2015.07.12

19         Cutroneo KR, Chiu JF. Comparison and evaluation of gene therapy and epigenetic approaches for wound healing. Wound Repair Regen 2000;8:494–502. doi:10.1046/j.1524-475X.2000.00494.x

20         Förster Y, Schmidt JR, Wissenbach DK, et al. Microdialysis sampling from wound fluids enables quantitative assessment of cytokines, proteins, and metabolites reveals bone defect-specific molecular profiles. PLoS One 2016;11:1–24. doi:10.1371/journal.pone.0159580

21         Zang T, Broszczak DA, Broadbent JA, et al. The biochemistry of blister fluid from pediatric burn injuries: proteomics and metabolomics aspects. Expert Rev Proteomics 2016;13:35–53. doi:10.1586/14789450.2016.1122528

22         Kalkhof S, Förster Y, Schmidt J, et al. Proteomics and Metabolomics for In Situ Monitoring of Wound Healing. Biomed Res Int 2014;2014:1–12. doi:10.1155/2014/934848


 

 

 

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Categorieën
Level 4

4 Redenen voor celdood

Voor de genezing van wonden is vijfennegentig van de honderd keer het ontdekken en wegnemen van de oorzaak voldoende. Als dat niet lukt kan een chronische wond ontstaan. Om dan gericht te kunnen interveniëren is sterk vereenvoudigde kennis van enkele processen op celniveau handig. Ik merk op nascholingen dat die kennis veel inzicht oplevert.

Basaal in het ontstaan en genezen van wonden is inzicht in de manier waarop cellen omgaan met stress. In de meeste wonden is in de wond rand geen abrupte overgang van gezond weefsel naar necrose maar is er een zone waarin de omstandigheden voor cellen steeds slechter worden. Die zone is onder te verdelen in een gezond deel, een deel onder stress, een deel wat herstelbaar schade heeft en een deel wat onherstelbare schade heeft. Deze zone indeling is voor ieder type weefsel anders waardoor bijvoorbeeld een ondermijning kan ontstaan doordat een onderliggend weefsel al onherstelbaar schade kent terwijl de schade van het bovenliggend weefsel nog herstelbaar is.

Cel-stress en -schade ontstaat vaak door de inwerking van krachten op het weefsel, zuurstofgebrek en/of gebrek aan voedingsstoffen. Stress en schade kunnen leiden tot celdood, de meest voorkomende manier van celdood is echter apoptose, geprogrammeerde celdood waarbij het lichaam ervoor kiest om cellen op te ruimen.

De inwerking van krachten op cellen leidt tot druk, trek- en schuifkrachten. Drukverhoging kan leiden tot het lek raken van de celmembraan, trekkrachten kunnen leiden tot het scheuren van cellen en schuifkrachten kunnen dat allebei doen. Bij de inwerking van krachten op cel lijkt druk de grootste oorzaak van problemen maar dat is waarschijnlijk niet het geval. Weefsels zijn vaak anisotroop is, dat betekent dat ze niet even sterk zijn in alle richtingen. Veel weefsels hebben een speciale constructie om krachten uit een bepaalde richting te verwerken. Als er uit een “verkeerde” richting aan een cel of weefsel wordt geduwd of getrokken kan zij gemakkelijk vervormen en beschadigen. Daarnaast leidt grotere vervorming vaak tot het lekken van de celmembraan waardoor er calciumionen in de cel komen wat direct leidt tot problemen[1,2]. De cel meet de krachten die op haar inspelen met de hulp van de celkern[3], daarmee kan ze vaststellen hoe groot de stress en schade is en reageren.

De beschikbaarheid van zuurstof kan ook voor problemen zorgen. Een humane cel is voor de zuurstofvoorziening vrijwel volledig afhankelijk van hemoglobine. Als een cel niet langer door rode bloedlichaampjes van zuurstof kan worden voorzien zal zij sterven. Problemen met zuurstof leiden op het algemeen tot problemen in het mitochondrion. Als een cel zuurstoftekort heeft zal het mitochondrion hierop reageren met aangepaste processen voor het blijven produceren van energie waarbij ook de reactieve zuurstofdeeltjes en stikstofoxiden ontstaan. Deze reactieve stoffen vertellen de cel en haar omgeving dat er sprake is van (oxidatieve) stress. Om dat te veel reactieve zuurstofdeeltjes leiden tot cel schade zorgen deze stoffen ook voor het activeren van het immuunsysteem zodat eventueel niet meer levensvatbare cellen worden opgeruimd. Hierdoor kan het weefsel ook met minder zuurstof blijven functioneren[4].

Gebrek aan bouw en brandstoffen kunnen het metabolisme in de cel verstoren waardoor een cel moeite krijgt om zichzelf in stand te houden. Hierbij wordt vooral de werking van het endoplasmatisch reticulum verstoord.

Het endoplasmatisch reticulum is belangrijk het cel metabolisme. Het heeft de rol van een chemische fabriek. Als het endoplasmatisch reticulum niet langer in staat is om haar werkzaamheden goed uit te voeren spreekt men van endoplasmatisch reticulum stress (ER-stress)[5].

Als nu een cel problemen krijgt door krachten, zuurstofgebrek of gebrek aan bouwstoffen, worden er allerlei stoffen in de cel geproduceerd die, als problemen groot zijn, de samenwerking van de celkern, de mitochondria en het endoplasmatisch reticulum verder verstoren[2]. Het is natuurlijk in het belang van een cel om ervoor te zorgen dat de omgeving weet van de problemen. De cel gaat signalen uitzenden waardoor omliggende cellen kunnen reageren. Deze signalen zijn heel specifiek zodat de omliggende cellen en de rest van het lichaam vrij nauwkeurig weten wat de problemen zijn[6,7].

Cellen zitten samen in een weefsel, om de kwaliteit van het weefsel in stand te houden is het zinvol zijn om cellen die niet goed functioneren op te ruimen. Dit is de meest voorkomende reden van celdood. Een cel wordt opgeruimd als zij versleten of beschadigd is, als zijn niet goed functioneert of als de huidige functionaliteit niet meer nodig is. Het lichaam ruimt cellen het liefst op een gecontroleerde manier op waarbij de cellen netjes worden afgebroken en gerecycled, apoptose. Als cellen niet netjes worden opgeruimd maar uiteen vallen spreekt men van necrose, ongecontroleerde celdood wat leidt tot het tot het vrijkomen van cel restanten in het weefsel. Deze resten die wijzen op ongecontroleerde processen te hebben een sterke signaalfunctie, dit zijn de zogenoemde damps en pamps (damage-associated molecular patterns en pathogen-associated molecular patterns).

Omdat de aanwezigheid van deze signalen wijst op ongecontroleerde omstandigheden reageert het lichaam hier met een sterke immuunrespons op. Zowel apoptose als necrose kennen een aantal varianten[8].

Het zal duidelijk zijn dat een cel niet meteen overlijdt aan druk, zuurstofgebrek of gebrek aan bouwstoffen. Op praktische gronden is een indeling te maken in stress (geen schade, eng stress) – verwonding (herstelbaar, eng injury) – schade (onherstelbaar – eng damage). Voor stress is geen regeneratie nodig, verwond weefsel is in principe volledig te regenereren, alleen beschadigd weefsel wordt niet volledig geregenereerd maar de belangrijkste functies worden hersteld. Overigens is het aangedane gebied dus vaak groter dan de wond zelf, op het oog vitaal weefsel hoeft dat niet te zijn.

Weefsel kan door zich snel aan te passen onder moeilijke omstandigheden overleven. Het lichaam houdt daarbij zorgvuldig de gebeurtenissen in de gaten en zal op basis van de signalen reageren. Het kan dan op korte termijn bijvoorbeeld cellen met signaalstoffen aansturen om met deze met minder zuurstof om te laten gaan, een bloedvat open te zetten of een immuunreactie te starten, op lange termijn kan het het weefsel aanpassen door bijvoorbeeld andere structuren te laten ontstaan. (extra bloedvaten om een tekort aan bloed te compenseren of collageen oriëntatie veranderen.)

Ongeacht hoe een wond is ontstaan, in het wondbed is door gebrek aan perfusie altijd sprake van tekorten aan zuurstof en bouwstenen, daarnaast is de extracellulaire structuur aan het wondoppervlak vaak verstoord waardoor ook veel vervorming van cellen optreedt. De structuren waarmee het lichaam normaal gesproken de toestand van het weefsel analyseert zoals sensoren, vaten en zenuwen ook beschadigd. De cellen rond om het wondbed, en dat is meer dan een paar millimeter, hebben door de schade aan het weefsel veel stress. Het zal duidelijk zijn dat beschadigde weefsels, structuren en cellen allemaal signalen uitzenden, deze kakofonie verstoord de communicatie tussen cellen en weefsels. Onder normale omstandigheden, dat wil zeggen in een jongere patiënt, zijn die problemen goed te hanteren. Zodra de wond groter en/of complexer is of de patiënt meer pathologie heeft kunnen de normaal soepel lopende processen voor de aanmaak van nieuw weefsel ineens niet meer soepel verlopen[9,10]. Sterker nog het kan zo zijn dat door “communicatiefouten” signalen verkeerd worden afgegeven of geïnterpreteerd. Dat lijkt wat abstract maar in de praktijk heet dat een chronische wond. Een niet goed aangestuurde ontstekingsreactie kan bijvoorbeeld tot dusdanig veel extra schade in het wondbed leiden dat de daarbij ontstane damps de (mogelijk steriele) ontsteking alleen maar verder aanjagen. Door het te laat reageren op zuurstofgebrek blijven bloedvaten soms te lang open staan waardoor reperfusion injury[11,12] kan ontstaan wat weer tot schade ergens anders in het lichaam kan leiden[13]. En door een wirwar aan signalen weten bijvoorbeeld stamcellen niet goed wat te doen. En dit zijn maar een paar van de vele oorzaken van een chronische wond.

Hoewel de onderliggende pathologie vaak verschillend is, kent de problematiek van chronische wonden op cel en weefselniveau verrassende overeenkomsten. Bovendien zijn veel van deze processen te beïnvloeden. Helaas ontbreekt het op de werkvloer vaak aan voldoende kennis over mogelijke interventies, bijvoorbeeld over pentoxifylline [14–16]. Er zijn nog tientallen gedocumenteerde medische interventies, zoals in dit voorbeeld pentoxifylline[16–18], beschikbaar. Ook op de andere 4 levels in de wondzorg is veel bekend.

Er is nog veel te ontdekken, gelukkig is ook veel nu al beschikbaar, het moet nog wel de werkvloer bereiken.

 

Literatuur:

1         Carafoli E, Krebs J. Why calcium? How calcium became the best communicator. J Biol Chem 2016;291:20849–57. doi:10.1074/jbc.R116.735894
2         Hill S, Van Remmen H. Mitochondrial stress signaling in longevity: A new role for mitochondrial function in aging. Redox Biol 2014;2:936–44. doi:10.1016/j.redox.2014.07.005
3         Belaadi N, Aureille J, Guilluy C. Under Pressure: Mechanical Stress Management in the Nucleus. Cells 2016;5:27. doi:10.3390/cells5020027
4         Schieber M, Chandel NS. ROS function in redox signaling and oxidative stress. Curr Biol 2014;24:R453–62. doi:10.1016/j.cub.2014.03.034
5         van Vliet AR, Agostinis P. When under pressure, get closer: PERKing up membrane contact sites during ER stress. Biochem Soc Trans 2016;44:499–504. doi:10.1042/BST20150272
6         Krebs J, Agellon LB, Michalak M. Ca2+ homeostasis and endoplasmic reticulum (ER) stress: An integrated view of calcium signaling. Biochem Biophys Res Commun 2015;460:114–21. doi:10.1016/j.bbrc.2015.02.004
7         Elks PM, Renshaw S a, Meijer AH, et al. Exploring the HIFs, buts and maybes of hypoxia signalling in disease: lessons from zebrafish models. Dis Model Mech 2015;8:1349–60. doi:10.1242/dmm.021865
8         Nikoletopoulou V, Markaki M, Palikaras K, et al. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta – Mol Cell Res 2013;1833:3448–59. doi:10.1016/j.bbamcr.2013.06.001
9         van Beek JHGM, Kirkwood TBL, Bassingthwaighte JB. Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance. Interface Focus 2016;6:20150079. doi:10.1098/rsfs.2015.0079
10       Yin F, Sancheti H, Liu Z, et al. Mitochondrial function in ageing: coordination with signalling and transcriptional pathways. J Physiol 2015;0:n/a-n/a. doi:10.1113/JP270541
11       Manson PN, Anthenelli RM, Im MJ, et al. The role of oxygen-free radicals in ischemic tissue injury in island skin flaps. Ann Surg 1983;198:87–90. doi:10.1097/00000658-198307000-00017
12       Lejay A, Meyer A, Schlagowski AI, et al. Mitochondria: Mitochondrial participation in ischemia-reperfusion injury in skeletal muscle. Int J Biochem Cell Biol 2014;50:101–5. doi:10.1016/j.biocel.2014.02.013
13       Mansour Z, Charles AL, Kindo M, et al. Remote effects of lower limb ischemia-reperfusion: Impaired lung, unchanged liver, and stimulated kidney oxidative capacities. Biomed Res Int 2014;2014. doi:10.1155/2014/392390
14       Sharma K, Ishaq M, Sharma G, et al. Pentoxifylline triggers autophagy via ER stress response that interferes with Pentoxifylline induced apoptosis in human melanoma cells. Biochem Pharmacol 2016;103:17–28. doi:10.1016/j.bcp.2015.12.018
15       Sharma R, Randhawa PK, Singh N, et al. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms. Eur J Pharmacol 2015;768:58–70. doi:10.1016/j.ejphar.2015.10.029
16       Jull A, Waters J, Arroll B. Pentoxifylline for treatment of venous leg ulcers: a systematic review. Lancet 2002;359:1550–4. doi:10.1016/S0140-6736(02)08513-6
17       Jull AB, Arroll B, Parag V, et al. Pentoxifylline for treating venous leg ulcers ( Review ). Cochrane database Syst Rev 2012;12:CD001733. doi:10.1002/14651858.CD001733.pub3
18       Falanga V, Fujitani RM, Diaz C, et al. Systemic treatment of venous leg ulcers with high doses of pentoxifylline: efficacy in a randomized, placebo-controlled trial. Wound Repair Regen 1999;7:208–13.

 

Categorieën
Level 4

Nerves and wound healing

Typically ignored is the role nerves have in  wound healing.

We always think that neuropathy has a role in the origin of wounds. That is not the whole story. It also has an influence on t5issue regeneration.

The best example of the importance of nerves on wound healing is in amphibians. Amphibians have the capacity for full regeneration. But only if the nerves are ok. No nerves, no limbs.(1)

In fetal wound care, you can observe another function of nerves. If you make a wound in an unborn lamb, the inflicted wound will be 14% smaller in a few days. But if you cut the nerve, the wound size will have increased by 60% in the same time. Somewhere this makes sense because you use muscle cells (myofibroblasts) for wound contraction. Muscle cells are guided by nerves.(2)

The myofibroblasts are not the only issues in a de-nerved wound. In these wounds you also have an increased amount of granulation tissue because both growth and death of new cells is not functioning properly. And all this tissue also leads to a larger scar.(3)

eh50341a54

But this is not all, as most of you know, nails and fingertips regenerate perfectly, even in humans. That is depending on how much tissue is lost and the age of the patient. Mouse research discovered central in this process is the formation of a blastema. This functions like a growing nucleus of mesenchymal cells. This is a very common process in nature, both in plants and animals.(4)

The blastema only functions when innervated. Regeneration will fail if there is no proper nervature in the tissue. Both in mice and men.(5) The pure blastema seems lost in mammalian skin regeneration. It is not lost completely because mouse strains with almost full regeneration exist. This is why there is attention for mesenchymal cells in regeneration.

Nerve cells are also involved in producing all kinds of inflammatory mediators. In the diabetic neuropathic skin impaired nerves cause all kinds of regulatory problems and are one of the many causes for impaired “diabetic” healing.(6) Research took off when doctors realised that paraplegics had impaired wound healing beyond the lesion in their spine.(7)

This was a clear indication of the importance of functional nerves on wound healing.

All in all the so-called type C-nerve fibres (pain) appear to have a larger than expected influence on wound healing. They do not only directly control cells and vessels, but also play a role in the organisation of the wound healing process by means of narrow mediators.  It influences on myofibroblast proliferation(8), mitosis and apoptosis, amount of granulation tissue

neuromediators

Leading to larger scars (l1), increased amount of granulation tissue (l2), is reduced re-epithelialisation (l2), reduced wound contraction (l3) reduced vasodilatation (l3) and reduced proliferation (l4). The good news is that new formation of these type of nerves can be stimulated with electricity.(9)

Before I started writing this little text I was not aware how much innovation influences wound healing. This is only a simple text, by no

This is only a simple text, by no means it is supposed to be the truth. Discussion is welcomed.

#proudtobeabiologist.

Nederlandse tekst op http://woundspecialist.eu/woundspecialist.eu/?p=550

References

  1. Cannata, S. M., Bagni, C., Bernardini, S., Christen, B. & Filoni, S. Nerve-independence of limb regeneration in larval Xenopus laevis is correlated to the level of fgf-2 mRNA expression in limb tissues. Dev. Biol. 231, 436–446 (2001).
  2. Stelnicki, E. J. et al. Nerve dependency in scarless fetal wound healing. Plast. Reconstr. Surg. 105, 140–7 (2000).
  3. Smith, P. G. & Liu, M. Impaired cutaneous wound healing after sensory denervation in developing rats: Effects on cell proliferation and apoptosis. Cell Tissue Res. 307, 281–291 (2002).
  4. Neufeld, D. A. Partial blastema formation after amputation in adult mice. J. Exp. Zool. 212, 31–36 (1980).
  5. Takeo, M. et al. Wnt activation in nail epithelium couples nail growth to digit regeneration. Nature 499, 228–232 (2013).
  6. Spenny, M. L. et al. Neutral endopeptidase inhibition in diabetic wound repair. Wound Repair Regen. 10, 295–301 (2002).
  7. Basson, M. D. & Burney, R. E. Defective wound healing in patients with paraplegia and quadriplegia. Surg. Gynecol. Obstet. 155, 9–12 (1982).
  8. Ashrafi, M., Baguneid, M. & Bayat, A. The Role of Neuromediators and Innervation in Cutaneous Wound Healing. Acta Derm. Venereol. (2014). doi:10.2340/00015555-2321
  9. Kao, C. H. et al. High-frequency electrical stimulation can be a complementary therapy to promote nerve regeneration in diabetic rats. PLoS One 8, (2013).