Pathophysiology of venous ulceration

Joel M. Crawford, Brajesh K. Lal, Walter N. Durán, Peter J. Pappas

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6 months to heal, and ulcer recurrence rates at 5 years are >58%. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals.

Original languageEnglish (US)
Pages (from-to)596-605
Number of pages10
JournalJournal of Vascular Surgery: Venous and Lymphatic Disorders
Volume5
Issue number4
DOIs
StatePublished - Jul 2017

Fingerprint

Varicose Ulcer
Ulcer
Iron Overload
Pathologic Processes
Dermis
Phenotype
Veins
Cytokines
Hypertension
Recurrence
Varicose Veins
Wound Healing
Patient Care
Leukocytes
Fibroblasts
Erythrocytes
Macrophages
Inflammation
Skin
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Crawford, Joel M. ; Lal, Brajesh K. ; Durán, Walter N. ; Pappas, Peter J. / Pathophysiology of venous ulceration. In: Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2017 ; Vol. 5, No. 4. pp. 596-605.
@article{9bfc0f33297242309f2511d774696688,
title = "Pathophysiology of venous ulceration",
abstract = "Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6 months to heal, and ulcer recurrence rates at 5 years are >58{\%}. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals.",
author = "Crawford, {Joel M.} and Lal, {Brajesh K.} and Dur{\'a}n, {Walter N.} and Pappas, {Peter J.}",
year = "2017",
month = "7",
doi = "10.1016/j.jvsv.2017.03.015",
language = "English (US)",
volume = "5",
pages = "596--605",
journal = "Journal of Vascular Surgery: Venous and Lymphatic Disorders",
issn = "2213-333X",
publisher = "Elsevier Inc.",
number = "4",

}

Pathophysiology of venous ulceration. / Crawford, Joel M.; Lal, Brajesh K.; Durán, Walter N.; Pappas, Peter J.

In: Journal of Vascular Surgery: Venous and Lymphatic Disorders, Vol. 5, No. 4, 07.2017, p. 596-605.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Pathophysiology of venous ulceration

AU - Crawford, Joel M.

AU - Lal, Brajesh K.

AU - Durán, Walter N.

AU - Pappas, Peter J.

PY - 2017/7

Y1 - 2017/7

N2 - Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6 months to heal, and ulcer recurrence rates at 5 years are >58%. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals.

AB - Our understanding of the pathophysiologic process of venous ulceration has dramatically increased during the past two decades because of dedicated, venous-specific basic science research. Currently, the mechanisms regulating venous ulceration are a combination of macroscopic and microscopic pathologic processes. Macroscopic alterations refer to pathologic processes related to varicose vein formation, vein wall architecture, and cellular abnormalities that impair venous function. These processes are primarily caused by genetic factors that lead to the destruction of normal vein wall architecture and venous hypertension. Venous hypertension causes a chronic inflammatory response that over time can cause venous ulceration. The inciting inflammatory injury is chronic extravasation of macromolecules and red blood cell degradation products and iron overload. Chronic inflammation causes white blood cell extravasation into the dermis with secretion of numerous proinflammatory cytokines. These cytokines transform the phenotype of fibroblasts to a contractile phenotype that increases tension in the dermis. In addition, iron overload keeps macrophages in an M1 phenotype, which leads to tissue destruction instead of dermal repair. Current surgical and medical therapies are primarily directed at eliminating venous hypertension and promoting venous ulcer wound healing. Despite advances in our understanding of venous ulcer formation and healing, ulcers still take an average of 6 months to heal, and ulcer recurrence rates at 5 years are >58%. To improve the care of patients with venous ulcers, we need to further our understanding of the underlying pathologic events that lead to ulcer formation, prevent healing, and decrease ulcer-free recurrence intervals.

UR - http://www.scopus.com/inward/record.url?scp=85020781492&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020781492&partnerID=8YFLogxK

U2 - 10.1016/j.jvsv.2017.03.015

DO - 10.1016/j.jvsv.2017.03.015

M3 - Review article

C2 - 28624002

AN - SCOPUS:85020781492

VL - 5

SP - 596

EP - 605

JO - Journal of Vascular Surgery: Venous and Lymphatic Disorders

JF - Journal of Vascular Surgery: Venous and Lymphatic Disorders

SN - 2213-333X

IS - 4

ER -