Part II: Wound healing: why wounds fail to heal, factors affecting wound healing, chronic wounds, non healing wounds.

In part 1- wound healing http://asktheburnsurgeon.blogspot.com/2010/03/wound-healing-scars-mature-scars.html we discussed the normal wound healing process and why scars result. However some wounds fail to heal and there are number of factors that hamper the normal wound healing process. It is important for us to recognize this so that we can address the problem. This article deals with: ‘why wounds fail to heal’ and answers questions that have been sent by the readers. 

 

Dear Doctor, I have a wound on my leg for the last two months. My diabetes is under control but my doctors say I need to undergo surgery to clean the wound. Doctor, can’t we just keep dressing the wound and get it to heal without surgery? I am scared of being cut up. Sandra F, Chicago, USA. 

A large number of patients go around from doctor to doctor with chronic nonhealing wound though their diabetes and other contributing factors are corrected. A look at this wound may show dead and devitalized tissue (slough, necrotic tissue) that releases endotoxins, which hamper the healing process (decreases epithelisation and fibroblast activity). Further a large number of traumatic wounds have some foreign bodies- like sand, dirt, glass pieces and others that get embedded within the wound during the accident. The presence of foreign bodies in the wound has been scientifically shown to increase the incidence of wound infection- which again hampers wound healing as we have already seen. Therefore it is logical that all the dead tissue and foreign bodies must be removed from the wound to help the healing process. Sometimes the cause of a non healing wound is an underlying bony infection (osteomyelitis) or infected fracture site that is constant discharging material (pus, serous fluid) that prevents the overlying wound from healing.

In all these cases the body can do nothing to heal the wound and we need external aid (see figure: why wounds fail to heal? at the end of this article)

Why call in the general surgeon? He will debride (remove all dead tissue) and clean up the wound using his knife. 

Why call the orthopedic surgeon? He will manage the underlying bone problem. He will treat the bone infection or the dead bone which prevents the wound from healing. 

Why call the vascular surgeon? If the blood flow to the limb or wound area is decreased or stopped due to diseased blood vessels, the vascular surgeon will evaluate (Doppler study / angiogram- will help to find if the blood vessels are patent and functioning) and repair these blood vessels to increase the blood flow (angioplasty or arterial bypass grafting) thereby removing the blockage and increasing the lumen of blood vessels or replacing the damaged or blocked blood vessels by a new blood vessel from the person’s own body or by using an artificial graft. The same is true for peripheral vascular diseases of the blood vessels that result in the poor blood supply to the wound.
 

Besides treating diabetes, can a physician help in wound healing? 

 We often feel that wounds are a surgeon’s domain. This is true to a great extent but in a number of patients there are a lot of general conditions and diseases of the body that affect the wound healing locally. In many patients the local factors in and around the wound appear not to be the cause of poor wound healing. These patients fail to realize that cause of their poor wound healing lie elsewhere. In patients with cardiac failure the heart is unable to pump the blood efficiently. The blood flow to the wound is poor and oxygen delivery to the tissue is decreased both of which impairs wound healing as we have discussed in detail. Further since the heart pump is ineffective, the back pressure (increased pressure in veins) cause more swelling (edema) of the tissues (and wound area). Tissue edema can also result in patients with renal failure where the kidneys fail to excrete the body wastes and urine. 

This swelling or edema is bad because a) It prevents good oxygenation of wound. b) It prevents the smooth flow of ‘worker cells’, ‘specialist cells’, growth factors and other repair materials into the wound area (refer part I wound healing http://asktheburnsurgeon.blogspot.com/2010/03/wound-healing-scars-mature-scars.html A physician, cardiologist or a nephrologist will need to assess and help to correct these problems. 

The same mechanism is true for patients with varicose veins.One of my patients, a healthy gentleman of 35 years, was going around with an accidental injury and wound on his leg for months. He had been on treatment for his diabetes (mild), and then treated with antibiotics, thinking it was infection till we evaluated his leg veins and found that he had underlying varicose veins without any apparent complaints, which was preventing the wound from healing. As the back pressure increases in the blood vessels some of the constituents of blood that normally does not pass through the wall (off capillaries) now filter out by pressure. This build up of fibrin, haemosiderin and fluid in the tissues cause firm swelling of the limb (induration) that is typically seen in blood outflow disorders (venous insufficiency). 

Why call the Plastic surgeon? 

Well, when large area of skin or tissue is lost the body cannot replace it. The human body only repairs the tissue – it cannot regenerate tissues. Therefore we need to replace skin or tissue loss from other areas of the human body by skin grafts or flaps (skin, fat, fascia, bone muscle etc): a plastic surgeon’s domain.

The plastic surgeon works on two basic principles: 1) What is the defect (tissue that needs to be replaced like skin, fat, bone, muscle, etc) 2) Replace the lost tissue by the same This is simple to understand: if your son has lost his shoes, you have to replace them with a new pair of shoes. You can’t buy him a pair of gloves instead!! Once the wound is cleaned of all dead tissue, we need to evaluate the defect and the missing tissue. The next step is to replace it. If skin is lost- replace skin, if muscle is missing- replace muscle, if bone is missing –replace with bone and so on. I hope this answers your question Ms Sandra. So go ahead and let your surgeon handle your wound.Why is blood supply to the wound area important? Blood vessels are like roads that lead ‘to and fro’ the damaged wound sites (see figure at end of article). The body sends workers and supplies to repair the damaged site by these blood vessels. Further adequate oxygen (carried by red blood cells) cannot reach the wound site and good oxygenation is required for proper functioning of all cells. If blood supply to the wound area is decreased from any reason then the ‘worker cells and specialist cells’ as well as nutrients and repair materials cannot easily reach the wound to begin the process of repair and healing effectively. 

Why do patients with diabetes have poor wound healing?

castor f

Brussels.

Thank you very much for your question Mr. Castor. 
 There are two issues that need to be addressed with respect to your burn 1) Diabetes 2) Smoking 
As we have discussed earlier, uncontrolled diabetes can be a great enemy of wound healing. If your diabetes is not under control you need to be seen by a physician or a diabetologist who will put you on proper medications to control the blood sugar. Smoking hampers wound healing and in fact the use of tobacco in any form must be avoided. This is because use of tobacco releases nicotine which in turn causes the blood vessels to contract (vasoconstriction) and reduce the blood flow to the wound. Similarly it also increases the platelet adherence (blood cells that stick together or clump together) which again diminishes the blood flow; all of which will lead to poor wound healing as already discussed. I understand that to quit smoking suddenly may be difficult, but you could reduce your frequency of smoking, or at least stop during the time your wound needs to heal. 

 

A non healing wound is often a pointer to the onset of diabetes or undetected underlying diabetes.

If the wound is infected, how will it affect the wound healing? Robin green,uk

When germs or microorganisms attack a wound and cause infection, they hamper the normal wound healing process. Some of them release toxin, damage the tissues, degrade growth factors, increase the collagen break down and also reduce the epithelisation: processes that are necessary to heal the wound. Even if the wound heals, in the presence of infection the chance of scar formation is higher. Further surgical procedure like skin grafting and flap that are carried out to heal the wound, which may be technically perfect may fail in the presence of infection. The skin graft fails to stick to the wound bed, floats or is eaten up. The skin flap may show inflammation and even areas of necrosis (tissue death).

What is atherosclerosis and how does it affect wound healing? 
 

Atherosclerosis is a condition usually seen in elderly individuals where blood flow is reduced due to the narrowing of the lumen of the blood vessels from abnormal depositions (atheromas) in the vessel wall. This result in reduced blood supply to the wound area which in turn hampers wound healing.

Should we use antibiotics if culture of wound fluid will show microorganisms? Well, one has to understand difference between wound colonization and wound healing. In wound colonization the germs are just visitors and don’t really damage the tissue, though they do have a potential to cause infection (become illegal residents). We avoid antibiotics in these cases and use local antimicrobial agents and dressings to cleanse the wound. However in wound infection, the germs have now become illegal residents of the wound and seek to damage and destroy tissue and prevent wound healing. These wound show signs of infection like redness, swelling (cellulitis), and foul smelling discharge; lacks peripheral epithelisation, has poor granulation, looks unhealthy and shows poor healing. 
In such cases we can start appropriate antibiotics based on the germs (organism) we culture from the wound.To confirm wound infection one can find the concentration of organism per gram of tissue (tissue culture) ; more than 10 to the power of 5 organisms is considered wound infection. We don’t do this commonly as clinical signs and symptoms are fairly accurate to know if the wound is infected. 


Doctor, if the patient has taken antibiotics can wound infection persists? 
Sunil P. Calcutta 

Yes, that often happens because: 1. Different germs or microorganisms are sensitive/ resistant to different antibiotics that are used to kill a specific germ. Therefore culturing the microorganism from the wound is very helpful and important. 2. Sometimes the wound may be infected with more than one germ, so that we may need a combination of antibiotics to treat the infection. 3. Also it is a good habit to repeat the wound cultures on weekly basis to know if new organisms are isolated or resistant micro bacteria are present so that we can attack these invaders. In major burn patients these issues are extremely important as the microbial pattern keeps changing due to a lot of dead tissue (burn eschar). 

 Doctor, I am a chain smoker and a diabetic. I suffered a 2nd degree burn on my left arm and its taking ages to heal. I just can’t quit smoking as my doctor advises. what should I do? Zubin S New Orleans USA 

Why is nutrition an important factor in wound healing?Stella Q scotland 

 This is easy to explain. For any tissue or body cell to repair and heal- proteins are needed. Amino acids (proline, glycine, lysine, etc) the building blocks for proteins are extremely crucial for cell function and repair. For repairing the cell wall fatty acids are needed. Vitamins and minerals play a great role in many chemical reactions that occur during various body metabolic processes. For example, Vitamin A (retinoic acid) – important for collagen production and epithelisation (surface cell growth). Vitamin E (alpha tocopherol) – antioxidant that destroys free radicals and helps healing. Vitamin C (ascorbic acid) – Helps collagen formation Iron, copper – helps collagen formation. Zinc- zinc is a constituent of many enzymes treated for wound healing as well as it is a potent antioxidant

If the patient has anemia (low hemoglobin), this will affect the oxygen carrying capacity of blood and the wound will get less oxygen resulting in poor healing. Albumin is another protein in the blood that is important for wound healing. Low levels of albumin can be detrimental to the wound healing process and should be corrected. In a patient with a non healing wound these factors need to be treated aggressively as they all contribute to non- healing. 

 Doctor, you said the growth factors play a big role in wound healing. Why don’t we supply them directly into the wound and hasten the healing? Sr. Mabel Minneapolis, USA 

We are still learning about the growth factors and our knowledge about them is limited. Here are few examples of growth factors.

: Vascular endothelial growth factor (VEgF) : Tranforming growth factor β (TGF β) : Epidermal growth factor (EGF) : Insulin like growth factor (Ig F-1) : Fibroblast growth factor (FGF) Platelet derived growth factor (PGF) : Tumor necrosis factor (TNF-α)

These are basically proteins but the body uses them to signal various activities like getting the ‘worker cells’ and ‘specialist cells’ to reach the wound site, encourage cells to start multiplying at the site (epithelisation), increase the blood flow by new blood vessel formation (angiogenesis) and stimulate fibroblast and other cells to repair the damaged area by collagen and ground substance formation. Their commercial production and use is still experimental and the first growth factor to reach the market is the platelet derived growth factor (PDGF) (regranex gel) (Becaplermin) developed by Johnson and Johnson. We need to develop the whole array of growth factors and see how effectively they will help wound healing. I think it will take sometime till we are able to use growth factors on a regular basis effectively. 

Doctor, can pressure cause ulcer or wounds?
 

Yes, when you apply pressure over an area of the body which is greater than the pressure within the blood vessels, the blood flow will diminish- this will reduce the oxygen supply and affect the metabolism and normal healing process which will ultimately result in breakdown of tissue and ulcer or wound formation. Such pressure ulcers commonly occur over the bony sites-(sacrum, shoulder blades, heel, back of head) in bedridden patients who are unable to move regularly to prevent sustained pressure over any particular area of the body. In these patients frequent change of position, maintaining hygiene, improving nutrition, using special mattress and beds to prevent sustained pressure over any specific site will help to prevent formation of pressure ulcer and also to heal them. However if a large nonhealing pressure ulcer should occur, you will need ‘external aid’ to heal them (see check list at end of article: why wounds fail to heal).


 Doctor, my father has a non healing wound that appeared without any apparent cause on his leg. He is not diabetic and is generally healthy. Can any infection start such a wound? Gunther P Berlin
 

This is an interesting question- a number of times we are unable to find the exact cause of the non healing wound. There are some infections that cause wounds or ulcers primarily. Yaws is a disease caused by a bacterium called a spirochete (a spiral-shaped type of bacteria). The bacterium is scientifically referred to as Treponema pertenue which can result in an ulcer. Mucormycosis is a disease caused by a fungus that can result in sinuses, abscesses and ulceration. Cutaneous anthrax (affecting the skin) is a disease caused by germ (bacillus) called Bacillus anthracis that can cause a skin wound. Actinomycosis is a disease caused by a germ (anaerobic bacteria) in individuals who have lowered immunity and results in sinuses and skin ulcers. Each of these diseases has investigations that will help to confirm the diagnosis. Sometimes the ulcer or wound may be the manifestation of an undetected disease in the human body. Pyoderma gangrenosum, a condition, which starts like a small swelling and then ends up as an ulcer often reveals underlying diseases like hepatitis, myeloma, systemic lupus erythematosis and others. There are other rare causes of wounds which like necrobiosis lipiodica, calciphylaxis, sickle cell ulcers etc. Please read this full article to check out the other causes including cancer that have been discussed. 

Doctor, can any medication cause an ulcer or wound? Rose A Argentina 

Well we rarely think of such a possibility. However anticoagulants like heparin or warfarin which are medications that reduce the blood coagulation ability (clotting) can induce skin necrosis (areas of skin destruction) that can end up as wounds.

Dear Doctor, my mother has an ulcer on the face that keeps on breaking down and does not heal for the past one year. The doctor says it may be a cancer as mom is 85 years old. What do you think? Patterson J Sydney, Australia

Thank you for your question. Yes, one of the causes of an ulcer or wound that fails to heal and keep on slowly increasing may be cancer or malignancy. The cancerous cells multiply from some signals and body is unable to stop this multiplication. However they increase and reach a stage where the blood flow cannot reach the cells adequately and so some of the cells start to die or form an ulcer or wound. While a cancer or malignancy can end up as an ulcer, a chronic wound can sometimes end up developing a cancer possibly due to the tissue being repeatedly damaged in the wound which excites the cells to multiply rapidly. Sometimes when there is a long standing scar (scar of many years) following burns or any other causes which is unhealthy (skin tends to breakdown often) a cancer can develop. This cancer that develops in the scar tissue or wound is called ‘Marjolins ulcer’.

When a cancer is suspected often a ‘biopsy’ will confirm it. The surgeon will either take a small part of the wound edge (incision biopsy) or if the ulcer is small –completely excise (excision biopsy) the ulcer. The pathologist can examine the tissue immediately while the surgery is ongoing – (frozen section) and give the surgeon a clue that the tissue is malignant or not. This will help the surgeon to decide how much area (free margin) he should excise (cut out) around the wound, as well as the depth, so the cancer is completely excised. In other cases the surgeon may decide to excise the wound and get the definite biopsy report (paraffin section) after a week or two with all tests confirming the nature and diagnosis of the cancer. So Mr. Patterson, if your doctor wants to go ahead with surgery, let him, as this will help the diagnosis and treatment. Sometimes you have to trust your surgeon! 


Dear doctor, Can radiation lead to poor wound healing?Alan Sebastin, Uk.

 This is a common question asked by patients of

cancer who undergo radiation and have skin ulcer or scar that breakdown and don’t heal. Radiation damages the blood supply in the radiated skin by causing direct destruction of the vessels and by causing clotting in the blood vessels (thrombosis and necrosis). Some also affect the DNA directly which prevents the cells from multiplying (cell proliferation). The hair follicles and fat cells are destroyed and the skin becomes thin (atrophic). These factors cause skin to breakdown and form radiation ulcers or wounds  









 Dear doctor, can emotional stress influence wound healing?

Well, when we suffer an injury or have a wound, most of us get depressed or undergo stress. It has been shown by that emotional stress hampers wound healing by increasing the blood pressure and blood levels of cortisol( steroids) , which in turn decreases our immunity. So guys sit back and relax when you have a wound (let the surgeon undergo stress!)

Dear Doc, what is lymphedema? Can it impair wound healing? 

While obstruction of veins can cause back pressure and swelling of the limbs, sometimes the drainage of tissue fluid (lymph) itself may be blocked or hampered leading to severe swelling of limbs (lymphedema). This is commonly seen when surgeons remove the lymph nodes in the axillary region (armpit) following cancer of the breast and the arm gets swollen. Sometimes diseases like filariasis(elephantiasis) block the lymphatic system, similarly causing lymphedema or swelling. In these cases if ulcers or wounds occur from any cause in these odematous limbs, their healing will be hampered. solving the mystery through simple exclusion, till the culprit is finally found and then exclaiming a) In diabetics the fine and big blood vessels that supply the wound are diseased (diabetic angiopathy) so that the blood flow to the wound is diminished. b) Further the disease affects the nerves (peripheral diabetic neuropathy) and this leads to increased tissue pressure as the pain sensations that tell us to relieve the pressure are affected or absent. In fact sensory loss or inability to feel pain sensation from any cause like nerve injury can result in ulcers or wounds that progress and don’t heal. As the person does not realize or feel the pain he fails to prevent repeated injury to himself. c) The immune system is affected in diabetes (decreased neutrophil function) so that there is a greater chance for germs (microorganisms) to attack the wound and cause infection. Many patients present with non healing wounds without prior history of diabetes.
 

 

 

Yes as we discussed before, fetal tissues( when baby in the womb) when injured heal perfectly- because these tissues have the ability to regenerate. At birth we loose this ability and our tissue can only repair- not regenerate new tissues or organs. When we become old ( old age) our skin is easily damaged. The ability of cells in old age to multiply is reduced. These factors lead to poor wound healing in old age. (There is still hope: our anti aging scientist are seriously involved in finding the secrets to eternal youth.) Dear doctor, if our immunity is lowered from any reason, will it affect wound healing?

Immunity deals with our ability to fight infection. Diseases like AIDS ( Acquired immune deficiency syndrome) directly attack the immune system and destroy it so that the immunity of these patients is impaired. Similarly taking steroids for long term (for any reason) can reduce the immunity again. Diabetes and malnutrition are other causes for decreased immunity as we discussed. If these patients have wounds obviously the healing will be hampered.

The checklist: why wounds fail to heal? from @asktheburnsurgeon

Sometimes finding the exact cause of a non healing wound can end up like an Agatha Christie novel where every character appears to be the culprit.

.......Was it Jane or Jack?... The killer knife which had ‘to Jane with love’ embossed in gold on the woodwork…. had been stolen from Sarah’s kitchen a month back……. was found in Jack’s drawer…… in a villa that was owned by Tim…. who had invited Michael, Peter &Stella for dinner….. On the night of murder…. the cook Burt who had recently changed his profession from being a butcher…...

The surgeon dealing with a non-healing wound has to be like Agatha Christie gathering all the characters in the plot; he should be Sherlock Holmes

‘'Elementary, my dear, Watson, elementary’’

I have gathered the characters responsible for chronic, delayed and non healing wounds and prepared a check list. While searching for causes of wounds or ulcers, the dictum is

''look for common disease or conditions and then if you are unable to find the cause or heal the wound, start looking for the rare ones'' When you are faced with a troublesome wound, look up the characters in the list that are likely to play a role in your patient’s wound, investigate each one, till you find the exact culprit. In this article I have tried to cover most of the common causes and I hope the reader will find the check list- ‘why wounds fail to heal’ helpful in treating their patients. Readers are welcome to send in their comments. With best regards, +@Asktheburnsurgeon Topics discussed in this article: why wounds fail to heal, chronic wounds, diabetic wound, infected wound, pressure ulcers, cancer, malignant wound, radiation ulcers, peripheral vascular diseases, vasculitis, wound infection, foreign bodies in wounds, varicose veins, venous ulcers, Deep vein thrombosis, lymphedema, renal failure, cardiac failure, anthrax, yaws, mucormycosis, actinomycosis, debridement, skin graft, flap cover, bone infection, thrombosed blood vessels, low hemoglobin, low albumin, low oxygenation, malnutrition, vitamin mineral deficiency, smoking, steroids, aging, immunocompromised – AIDS, immune suppression, medical illnesses, emotional stress, self induced wounds, non healing wounds. keyword: wound, wounds