Venous ulcers form secondary to ischemia caused by venous hypertension and resulting hypoxia in the tissues. Venous hypertension increases hydrostatic pressure in the veins, reducing blood flow and oxygen diffusion at the capillary level. This leads to hypoxia, inflammation, and the deposition of fibrin around capillaries. Fibrin cuffs further decrease oxygen permeability and trap inflammatory cells and growth factors. Over time, the microcirculation is damaged, endothelial function declines, and tissue fibrosis develops, perpetuating the hypoxic and inflammatory environment that prevents wound healing and leads to chronic venous ulcers. Managing venous hypertension and improving microcirculation through compression therapy and addressing venous reflux are key to treating venous leg ulcers.

1. Why are Venous Ulcera0ons
Secondary to Ischemia?
Rodrigo Kikuchi
Instituto de ExcelênciaVascular - Londrina/PR - Brazil
Clínica ExcelênciaVascular - São Paulo/SP - Brazil
Comission of Venous Disease - Brazilian Society for Angiology andVascular Surgery
Member ACP, SVS,AVF,AFI

2. Consulting and training:
- MEDI
- Sigvaris
- Servier
- Aché
- Vydence Lasers
- ORlight Lasers
- Alma Lasers
- Cutera
- Medtronic

3. Capillaries: where real interaction occurs
Microcirculation
arterioles venules

4. Aorta = 33cm/sec
GUYTON, A; HALL, J. Textbook of Medical Physiology. 2016. ed 13. p 170.
Capillaries = 0.3mm/seg
length 0.3 a 1mm
blood stays for 1-3 seconds
20%
64%
5 L of blood

5. - pressure that’s gravity exerts on a liquid column
Hydrostatic pressure
feet veins= 90mmHg
GUYTON, A; HALL, J. Textbook of Medical Physiology. 2016. ed 13. p 185.
Right atrium = zero
blood column weight = 80mmHg
post capillary pressure = 10mmHg

6. 15 - 30mmHg
(pregnancy, obesity, tumors, ascites…)
Retrograde pressures from abdomen
Supine = 5-6mmHg (Abdominal pressure)
higher pressure in lower limbs veins

7. “Residual force of the arterial pressure after passing the
capillaries”
This residual pressure is transmitted to the venules (post-capillaries)
Vis a Tergo
Works in all body position
10mmHg

8. H. Partsch, E. Rabe, R. Stemme. Compression Therapy of the Extremities.
Edition Phlebologiques Françaises. p.28
10mmHg

9. failure in arteriolar function
Vis a Tergo
high venous pressure
hypoxia

10. H. Partsch, E. Rabe, R. Stemme. Compression Therapy of the Extremities.
Edition Phlebologiques Françaises. p.44

11. Lancet. 1982 Jul 31;2(8292):243-5.
- extravasation of cells
and proteins
fibrin layer
barrier

12. There was deposition of fibrin around the capillaries in the central
part of the ischaemic ulcers, and the venous hypertension ulcers,
and in the non-ulcerated skin around one of the venous
hypertension ulcers and two of the ischaemic leg ulcers.
British Journal of Dermatology (1992) 126. p.582-585.
similarity between arterial end venous ulcers

13. Partsch H. Hyperaemic hypoxia in venous ulceration. Br J Dermatol
1984; 110: 249-50.
- 12.9+12.5 mmHg venous ulcers
- 9.7+ 11.2 mmHg arterial ulcers
Transcutaneous oxigen pressure
59.6+ 11.2 mmHg normal
after O2 inhalation
123.8+97.8 mmHg
venous ulcers
27.0+25.1 mmHg
arterial ulcers
in venous ulcer there is a gas diffusion problem
in arterial ulcer there is a transportation problem

14. Cardiovasc Surg (2000) Aug (5), 372-380
higher fibrin scores being associated with a reduction in the
oxygen diffusing capacity of the affected skin
evidence of pericapillary fibrin deposition somewhere in the
dermis of the ulcer bearing
- locals with “normal" skin in patients with healed ulcers

15. Fibrin cuff theory
- fibrin gets deposited around capillary leading to elevated intravascular pressure
- increased fibrinogen deposition in the interstitium
- the “fibrin cuff” decreases oxygen permeability 20-fold
Vasudevan B. Indian Dermatol Online J. 2014 Jul-Sep; 5(3): 366–370
Inflammatory trap theory
- growth factors and inflammatory cells get trapped in the fibrin cuff
- severe uncontrolled inflammation in surrounding tissue
- proteolytic enzymes and reactive oxygen metabolites are released
- occlusion by leukocytes.
Dysregulation of various cytokines
- Dysregulation of various pro-inflammatory cytokines and growth factors like
tumor necrosis factor-α (TNF-α),TGF-β and matrix metalloproteinases lead to
chronicity of the ulcers.
hypoxia
hypoxia

16. Raffetto JD. Plast Reconstr Surg 127 (suppl): 279S, 2011

17. Venous hypertension
Endothelial activation
Inflammation
mast cels,T, cels, macrophages
TNF, IL-1, MMPs,TGF
Fibroblasts MMPs
Fibrosis
Chronic venous ulcer
Raffetto JD. Plast Reconstr Surg 127 (suppl): 279S, 2011
hypoxia

18. Microcirculation (2000) 7, S3–S12
The microangiopathic changes observed with worsening clinical symptoms:
- decrease in the number of capillaries,
- glomerulus-like changes in capillary morphology,
- a drop in the oxygen content (tcpO2) of the skin,
- increased permeability of the capillaries to low-molecular weight
substances,
- diminished vascular reserve.
Increased endothelial expression of ICAM-1,VCAM-1, and E-Selectin
Leukocyte adhesion

19. Wounded legs exhibited the largest decrease in blood
perfusion under both normal and combined loadings
Clin Biomech 2015 Dec;30(10):1218-24.
loading simulates forces to
those that the leg might
experience during normal
living, such as crossing one’s
legs or resting one’s leg on a
couch

20. valvar reflux venous obstruction
Increase in ambulatory venous pressure
(venous hypertension)
Edema
Skin alterations
- Ocre dermatitis
- Fibrosis
Ulcer
muscle pump failure

21. H. Partsch, E. Rabe, R. Stemme. Compression Therapy of the Extremities.
Edition Phlebologiques Françaises. p.44

22. H. Partsch, E. Rabe, R. Stemme. Compression Therapy of the Extremities.
Edition Phlebologiques Françaises. p.44

23. GUYTON,A; HALL, J.Textbook of Medical
Physiology. 2016. ed 13. p 199.
edema increase in interstitial pressure
microcirculation disregulationhypoxia

24. JVasc Surg:Venous and Lym Dis 2017;5:596-605
sustained inflammatory injury (cytokines, inflammatory cells, macromolecules…)
microcirculatory dysfunction
Macroscopic alterations (valve failure, varicose vein, venous insufficiency)
venous hypertension
hypoxia
- venous reflux (foam, ablation,
surgery)
- vein pump (muscle, mov. range)
- compression
[

28. In conclusion
- the understanding of patophysiology of venous ulcers has advanced in
the past years
- knowledge about cytokines, inflammation modulation, phenotype
manifestations, cells interactions is increasing and may lead to new
therapies modalities
venous hypertension tissue ischemia
cytokines
inflammation
phenotypecells
macromolecules

29. kikuchi@excelenciavascular.com.br
+55 11 98111-9901
www.excelenciavascular.com.br
www.evascursos.com.br
Why are Venous Ulcera0ons Secondary
to Ischemia?