Commentary
BLOOD SUPPLY AND DECUBITUS ULCERS
TERENCE J, RYAN, D.M.
One of the best recognized and the most universal example of tissue necrosis is the bed sore. It is due to temporary cessation of the blood supply and is determined by a degree of pressure for a given period of time. Husain showed that some of the damage is due to reperfusion after the release from pressure.' It is at this stage that the vessel walls leak and particulate matter such as bacteria tend to be localized therein. He also showed that the threshold tolerance to the amount of pressure was drastically lowered by a previous vascular insult such as ligation of the femoral artery which initially did not cause necrosis. This finding is important in clinical vascular pathology where the majority of occlusions that result in total ischemia occur in organs which are usually supplied by arteriosclerotic vessels and have probably been subjected to previous sublethal amounts of ischemia.^ A study on normal and paraplegic swine^ demonstrated that external pressure applied to the skin above 150 mm. Hg, in conjunction with friction for Vh hours, resulted in superficial epidermal necrosis seven days later. Others have drawn attention to the importance of skin abrasion and the influence of repetitive moderate mechanical stress.* Separation of endothelial cells lining the microcirculation was Address for reprints: T. |. Ryan, Consultant Dermatologist, the Department of Dermatology, The Slade Hospital, Headington, Oxford OX3 7|H England.
?rom the Department of Dermatology, The Slade Hospital, Headington, Oxford, England
observed with consequent aggregation of platelets and occlusion of the vessel. Cherry and Ryan,^ studying the effect of ischemia on the skin, found that occlusion of the vessel by clotting was not so much an immediate effect of ischemia, but followed shedding of the damaged endothelium on reperfusion. Klenerman" observed that a period of ischemia resulted in increased blood fibrinolysis but Larsson and Risberg,^ studying the human legfollowing ischemia and reperfusion during menisectomy, noted that release of factor VIM from endothelial cells and still later impairment of fibrinolysis occurred during the reperfusion phase. If exhaustion of fibrinolytic activators from endothelial cells is a partial explanation ofthechanges in decubitus ulcers, then other factors contributing to such exhaustion may be important. Damage to the epidermis results in a complete loss of fibrinolysis in the upper dermis some six to twelve hours later; abrasion is particularly harmful.** The increased leakiness of vessels damaged by ischemia enhances the localization of noxious circulating agents. This leads to pathology from bacteria, immune complexes or platelet aggregation,^ and it is not surprising that dis-
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INTERNATIONAL JOURNAL OF DERMATOLOGY
eases such as septicemia or rheumatoid arthritis have a higher incidence of complicated pressure sores. Studies on repetitive injury ^ emphasize the heightened vulnerability of tissues that have experienced previous injury of any kind sufficient to cause blood stasis. The Shwartzmann phenomenon, gravitational stasis, the delayed skin flap, cold and a variety of other kinds of injury are preparatory in this respect. In the prevention and management of decubitus ulcers, pressure remains the single most important factor. However, the importanceofeven minor injury to the epidermishas probably been underestimated and the effects ofrepetitiveischemicinsu'ltsareclearly important. A good physician will keep a careful watch on many factors, including blood pressure, infection, anemia and associated immune disease.
March 1979
Vol. 18
References 1. Husain, T.: An experimental study of some pressure effects on tissues with reference to the bedsore problem. J. Pathol. Bact. 66:347, 1953. 2. Ellis, H.: Arteriosclerotic occlusion in the lower limb. Ann. Roy. Coll. Surg. 49:137, 1971. 3. Dinsdale, S.: Decubitus ulcers in swine; light and electron microscopic study of pathogenesis. Arch. Phys. Med. Rehab. 54:51, 1973. 4. Brand, P. W.: Pressure sores—the problem. In: Bed Sore Biomechanics. Edited by Kenedi, R. M., Cowden, J.M., and Scales, J.T. London, Macmi I Ian, 1976, p. 19 5. Cherry, G. W., and Ryan, T. J.: The Effect of ischemia and reperfusion on tissue survival. Maj. Probl. Dermatol. 7:93, 1976. 6. Klenerman, K.: Prophylaxis against deep vein thrombosis. Lancet 1:970, 1977. 7. Larsson, J., and Risberg, B.: Ischemia induced changes in tissue fibrinolysis in human legs. Biblio. Anat. 15:556, 1977. 8. Ryan, T. )., NIshioka, K., and Dawber, R. P. R.: Epithelial—endothelial interactions in the control of inflammation through fibrinolysis. Br. ). Dermatol. 84:501, 1971. 9. Kanan, M. W., and Ryan, T.). Eds.: The localization of granulomatous diseases and vasculitis in the nasal mucosa. In: Microvascular Injury. Philadelphia, Saunders, 1976, p. 195.
Vaginal Absorption
The cream vehicle appears to retard the vaginal absorption of micronized estradiol. The levels of estradiol and estrone attained with the 2 mg dose of estradiol cream are achieved with the application of one-fourth (0.5 mg) the amount of micronized estradiol suspended in saline. In either case, these estrogen levels are clearly supraphysiologic. However, with the 0.2 mgdose of estradiol in a cream, a near physiologic concentration of the hormone (80 ± 8.5 pg/ml) is attained with a proportionally smaller rise of estrone (41 ± 3.8 pg/ml) owing to the limited substrate for conversion. These levels of estradiol and estrone are essentially those of the follicular phase in women with normal cycles. Thus, intravaginal application of micronized estradiol cream at the 200 /Ltg dose may be considered physiologically appropriate for estrogen replacement in deficiency states. It is clear that the biologic effect of intravaginally administered estrogen cream is mediated principally through delivery to target cells by the circulation. The assumed topical effects, if present, should be relatively small. Thus, caution must be exercised when vaginal estrogen cream is used to manage estrogen deficiency in the presence of estrogen-dependent neoplasms.—Riggs, L. A., Hermann, H., and Yen, S. S. C : Absorption of estrogens from vaginal creams. N. Engl. j . Med. 298:197, 1978.
BLOOD SUPPLY AND DECUBITUS ULCERS
TERENCE J, RYAN, D.M.
One of the best recognized and the most universal example of tissue necrosis is the bed sore. It is due to temporary cessation of the blood supply and is determined by a degree of pressure for a given period of time. Husain showed that some of the damage is due to reperfusion after the release from pressure.' It is at this stage that the vessel walls leak and particulate matter such as bacteria tend to be localized therein. He also showed that the threshold tolerance to the amount of pressure was drastically lowered by a previous vascular insult such as ligation of the femoral artery which initially did not cause necrosis. This finding is important in clinical vascular pathology where the majority of occlusions that result in total ischemia occur in organs which are usually supplied by arteriosclerotic vessels and have probably been subjected to previous sublethal amounts of ischemia.^ A study on normal and paraplegic swine^ demonstrated that external pressure applied to the skin above 150 mm. Hg, in conjunction with friction for Vh hours, resulted in superficial epidermal necrosis seven days later. Others have drawn attention to the importance of skin abrasion and the influence of repetitive moderate mechanical stress.* Separation of endothelial cells lining the microcirculation was Address for reprints: T. |. Ryan, Consultant Dermatologist, the Department of Dermatology, The Slade Hospital, Headington, Oxford OX3 7|H England.
?rom the Department of Dermatology, The Slade Hospital, Headington, Oxford, England
observed with consequent aggregation of platelets and occlusion of the vessel. Cherry and Ryan,^ studying the effect of ischemia on the skin, found that occlusion of the vessel by clotting was not so much an immediate effect of ischemia, but followed shedding of the damaged endothelium on reperfusion. Klenerman" observed that a period of ischemia resulted in increased blood fibrinolysis but Larsson and Risberg,^ studying the human legfollowing ischemia and reperfusion during menisectomy, noted that release of factor VIM from endothelial cells and still later impairment of fibrinolysis occurred during the reperfusion phase. If exhaustion of fibrinolytic activators from endothelial cells is a partial explanation ofthechanges in decubitus ulcers, then other factors contributing to such exhaustion may be important. Damage to the epidermis results in a complete loss of fibrinolysis in the upper dermis some six to twelve hours later; abrasion is particularly harmful.** The increased leakiness of vessels damaged by ischemia enhances the localization of noxious circulating agents. This leads to pathology from bacteria, immune complexes or platelet aggregation,^ and it is not surprising that dis-
0011-9059/79/0300/0123/$00.60 © International Society of Tropical Dermatology, Inc.
123
124
INTERNATIONAL JOURNAL OF DERMATOLOGY
eases such as septicemia or rheumatoid arthritis have a higher incidence of complicated pressure sores. Studies on repetitive injury ^ emphasize the heightened vulnerability of tissues that have experienced previous injury of any kind sufficient to cause blood stasis. The Shwartzmann phenomenon, gravitational stasis, the delayed skin flap, cold and a variety of other kinds of injury are preparatory in this respect. In the prevention and management of decubitus ulcers, pressure remains the single most important factor. However, the importanceofeven minor injury to the epidermishas probably been underestimated and the effects ofrepetitiveischemicinsu'ltsareclearly important. A good physician will keep a careful watch on many factors, including blood pressure, infection, anemia and associated immune disease.
March 1979
Vol. 18
References 1. Husain, T.: An experimental study of some pressure effects on tissues with reference to the bedsore problem. J. Pathol. Bact. 66:347, 1953. 2. Ellis, H.: Arteriosclerotic occlusion in the lower limb. Ann. Roy. Coll. Surg. 49:137, 1971. 3. Dinsdale, S.: Decubitus ulcers in swine; light and electron microscopic study of pathogenesis. Arch. Phys. Med. Rehab. 54:51, 1973. 4. Brand, P. W.: Pressure sores—the problem. In: Bed Sore Biomechanics. Edited by Kenedi, R. M., Cowden, J.M., and Scales, J.T. London, Macmi I Ian, 1976, p. 19 5. Cherry, G. W., and Ryan, T. J.: The Effect of ischemia and reperfusion on tissue survival. Maj. Probl. Dermatol. 7:93, 1976. 6. Klenerman, K.: Prophylaxis against deep vein thrombosis. Lancet 1:970, 1977. 7. Larsson, J., and Risberg, B.: Ischemia induced changes in tissue fibrinolysis in human legs. Biblio. Anat. 15:556, 1977. 8. Ryan, T. )., NIshioka, K., and Dawber, R. P. R.: Epithelial—endothelial interactions in the control of inflammation through fibrinolysis. Br. ). Dermatol. 84:501, 1971. 9. Kanan, M. W., and Ryan, T.). Eds.: The localization of granulomatous diseases and vasculitis in the nasal mucosa. In: Microvascular Injury. Philadelphia, Saunders, 1976, p. 195.
Vaginal Absorption
The cream vehicle appears to retard the vaginal absorption of micronized estradiol. The levels of estradiol and estrone attained with the 2 mg dose of estradiol cream are achieved with the application of one-fourth (0.5 mg) the amount of micronized estradiol suspended in saline. In either case, these estrogen levels are clearly supraphysiologic. However, with the 0.2 mgdose of estradiol in a cream, a near physiologic concentration of the hormone (80 ± 8.5 pg/ml) is attained with a proportionally smaller rise of estrone (41 ± 3.8 pg/ml) owing to the limited substrate for conversion. These levels of estradiol and estrone are essentially those of the follicular phase in women with normal cycles. Thus, intravaginal application of micronized estradiol cream at the 200 /Ltg dose may be considered physiologically appropriate for estrogen replacement in deficiency states. It is clear that the biologic effect of intravaginally administered estrogen cream is mediated principally through delivery to target cells by the circulation. The assumed topical effects, if present, should be relatively small. Thus, caution must be exercised when vaginal estrogen cream is used to manage estrogen deficiency in the presence of estrogen-dependent neoplasms.—Riggs, L. A., Hermann, H., and Yen, S. S. C : Absorption of estrogens from vaginal creams. N. Engl. j . Med. 298:197, 1978.
