By definition, an ulcer is a disruption of the inner lining of an organ or the outer covering like you have in the skin. As a rule, an ulcer has a base known as the ulcer crater and the surrounding edges of living and dead cells. Most ulcers are infected with both anaerobic and aerobic organisms. In diabetes mellitus, ulcers can be found anywhere, from the scrotum, known as Fournier’s ulcer, from a gangrene to the gluteal (bottom) region resulting from an injection. This has sometimes turned out to be catastrophic.
Diabetic foot ulcers occur in two out of every 10 diabetics in a life time. It is a major complication of the disorder and the leading cause of amputation (cutting off the leg). This ulcer can occur at any location in the in the leg, but commonly around pressure points on the leg and bony prominence. You find them under the foot, by the sides of the leg and also in the heel region. Apart from the foot, diabetic ulcer can occur anywhere in the body .The response is basically the same, in terms of inflammatory response and delayed wound healing.
One of the main causes of diabetic foot ulcer is diabetic neuropathy. This implies the damage of nerves by the disease process thereby leading to impairment of the functions of the area supplied by the nerve. Most long standing diabetics would tell you that from time to time, they do feel loss of sensation in their legs. The area may be completely numb. This is just one of the numerous symptoms of diabetic peripheral (outward) neuropathy. The other well known is a sudden tingling sensation or sharp pains. The consequence of this is that a person may sustain an injury and is completely unaware of it until life-threatening infection sets in.
Diabetes is a known cause of peripheral vascular disease. This condition results from narrowing of the blood vessels or their complete blockage (occlusion). The development of this phenomenon is proportional to the duration of the disease and its severity. In diabetes, this causes a dysfunction of the inner lining of the blood vessels and smooth muscle. This ultimately leads to ischaemia (oxygen lack) of the surrounding tissue and their eventual death, decay, ulceration and infection. Commonly you have a combination of nerve damage and vessel (vascular) narrowing leading to ulceration, aptly described as neurovascular.
Cell death in living person for the mention is known as necrosis. For the completion of this list, the worse culprits in the development of diabetic foot ulcer are excessive alcohol consumption and heavy cigarette smoking.
In the development of diabetic foot ulcer, it is important to appreciate the dynamics of a compartment in the body known as the extracellular matrix. This compartment lies between the epidermis, the outer surface of the skin and the dermis; just below it. The epidermis and the dermis together make up the skin. The extracellular matrix is composed of molecules produced by adjacent cells of the skin but mainly dominated by collagen and integrins that anchor cells in the extracellular matrix. The healing of wounds is powered by the biological activities that take place in the extracellular matrix.
These involve breaking down the matrix that has been damaged by a challenge as listed previously in diabetes and any other traumatic event. These damaged cells are evacuated and replaced; and as a rule increasing in number as a response to the harm perpetrated. This is a complex process that involves the matrix, the cells growing on and through the matrix. In the early phase of the assault, some of the cells that are called to play are the white blood cells, especially the pus forming neutrophils and the scavenger macrophages (large white blood cells that engulf unwanted materials and organisms in the body).
These subsequently activate the fibrous tissue forming fibroblast, which lay down new collagen. Simultaneously is the proliferation of blood vessels in the matrix, a process known as angiogenesis. The outlook of the product at this stage is granular in consistency and appearance, which gives it the name granulation tissue. The process is a lot more complex than is simply described here. Diagnosis would like you to imagine an evening out with a symphony orchestra in full musical concert. Here everyone has a musical sheet of his part in front of him – the violinist, the trumpeter, and guitarist etc, doing their thing. Then there is this man or woman, backing the audience with a funny looking dovetail suit, jerking and gesticulating with his hands and a small stick. That is the musical conductor of the symphonic orchestra. That is the role of the extracellular matrix! He harmonises everything and brings good music to our ears. Wound healing is therefore a regulated phased replacement of extracellular matrix components. This, in normal circumstances, would involve granulation, re-epithelisation (production of epithelium that covers the surface) and final remodeling.
Diabetes mellitus is a metabolic disorder. In metabolism, two main processes are involved. The first is when the body is practically building or making new substances as seen in growth and body repair. This, in most cases, is powered by growth hormone. This process is known as anabolism. The second aspect of metabolism is catabolism. In this situation, large molecules are broken down to smaller components either to be turned into waste materials, recycled or in some positive sense production of energy. All metabolic activities are enhanced by hormones and enzymes.
In diabetes mellitus, due to derangement of glucose metabolism, there is a tendency for other substances like protein and fat to be simultaneously affected. As a result of this, we have situations where high molecular weight sugars like aldose bind to proteins. These compounds made of sugar and protein is known to be structurally very stable and tend to accumulate on cell membranes. These large molecules are known to slow down the activities of the extra cellular matrix. Another example of this is where there is a failure of production of nitrous oxide, which is an important stimulant in the production of fibroblast and new blood vessels (angiogenesis).
During healing, damaged extracellular has to be degraded and this is carried out by the enzyme matrx metalloproteinase. This enzyme also helps in fibroblast migration, tissue reorganisation and remodeling. These activities are reversed by tissue inhibitor metalloproteinases. For some unknown reasons, there is over expression of matrix metalloproteinase in chronic diabetic ulcer. For proper wound healing, there has to be a balance in the activities of both enzymes and not absolute concentration. This is not so in diabetes mellitus. There are other metabolic disturbances in diabetic ulcer that cannot be explained here due to space constraint.
With regards to infecting organisms in diabetic foot ulcer and attendant cellulitis, most experienced physicians know that commonly in the flora are staphylococcus and streptococcus species. These are both gram positive bacteria. The implication of this is that they cause their harmful effect by producing exotoxins.
And two of the exotoxins produced by the streptococcus are streptokinase and streptodornase. These substances are known to break down blood clots and fibrin and connective tissues. They can be useful in the early phase of vascular accidents but in infections can undermine the matrix leading to rapid spread of infection.
Thus in diabetic ulcer so many factors can lead to discordant tone. The way out next week, see you then.