Wound healing

an overview
Kiki Lukman, Department of Surgery Medical School of Padjadjaran University/ Hasan Sadikin Hospital Bandung

Learning Objectives (1) :

At the end of the block, the learner will be able to :

Describe the basic concepts of cellular & biomolecular

mechanisms of normal skin wound healing. Explain the wound healing phases Explain the clinical implications of the basic science concepts of skin wound healing Compare and contrast between primary wound healing with healing with secondary intention

Learning Objectives (2) :

At the end of the block, the learner will be able to :

Apply the basic science concepts to the

management of wound healing Describe the cellular and molecular events of peritoneal adhesion/healing Explain the adhesion prevention measures Apply the basic science concepts to the management of problems due to complicating adhesions

Introduction

Wound healing :
Fundamental homeostatic process in response to

injury The understanding is fundamental to all of surgery Involves cellular & molecular events Specific wound healing process : skin, peritoneum, bone fracture, liver

The regulation of cells population

Normal Homeostasis

Cell signaling system

Extracellular matrix

Influence of ECM & GFs

Tissue remodeling

Normal wound healing

PLATELET GRANULES AND MEDIATORS OF PLATELET AGGREGATION

PLATELET GRANULES a. Granules: Contain PlateletSpecific Proteins Platelet factor 4 b-Thromboglobulin Platelet-derived growth factor Transforming growth factor b. Dense Granules Adenosine diphosphate Serotonin Calcium MEDIATORS OF PLATELET AGGREGATION Thromboxane A2 Thrombin Platelet factor 4

Primary wound healing

Collagen type III

Development of tensile strength

Healing with 2nd intention

Open wound healing

Factors that retard wound healing

Local Factors
Blood supply Mechanical stress

Denervation
Local infection

Necrotic tissue
Protection (dressings)

Foreign body
Hematoma

Surgical techniques
Type of tissue

Factors that retard wound healing

Systemic Factors
Age Anemia Drugs (steroids, cytotoxic medications, intensive antibiotic therapy) Malnutrition Obesity Systemic infection Temperature Trauma, hypovolemia, and hypoxia Genetic disorders (osteogenesis imperfecta, Ehlers-Danlos syndromes, Marfan syndrome) Hormones Diabetes Malignant disease Uremia Vitamin deficiency (vitamin C) Trace metal deficiency (zinc, copper)

Chronic Wound

Fails to heal within 3 months Classification :

pressure sores,diabetic foot, leg ulcers

Most have the potential to heal Due to inadequate cleansing, debridement, edema control, treatment of ischaemia, & achievement of moist wound healing. Increased proteases & collagenase, but decreased growth factors

Problems :

Discuss :
Factors influencing wound healing process Wound management Excessive Scarring

Peritoneal healing

What is peritoneal adhesions ?

Peritoneum :
Serosal membrane that is derived from

mesodermal tissues and contains mesothelial cells covering the visceral organs and abdominal wall.

Peritoneal adhesions :
Abnormal fibrous adhesions that adhere peritoneal

surfaces.

What are the causes ?

Congenital : Lads Band Acquired :

After surgery (79 - 92%) Post infection : diverticulitis, typhoid After radio theraphy. Allergy

Why does adhesion occur ?

It is due to vascular responses to

Peritoneal tissues ischemia Foreign bodies Inflammation Injury Blood

The balanced process between fibrin formation against fibrinolysis.

Inflammatory and Exudation of Fibrin

PMN Phagocyt PMN FIBRIN

Activity of Cytokine IL-1, IL-6, TNF- in inflamatory exudate, activated Macrophag and PMN release of : kinine, histamin, prostaglandines, NO, free radicals etc.

Modification to classical pathway

Cited : TreutnerKH, Schumpelick V (eds). Peritoneal Adhesions. Springer, Berlin, 1997 .

ACTIVATION OF FIBRINOLYTIC & ANTIFIBRINOLYTIC OF PERITONEAL MEMBRANE

Plasminogen Activators (t-PA, u-PA)
Source : mesothel and endthelial cells of blood vessel in sub-mesothelial

PAI-1, PAI-2 ( Injury to peritoneal)

Source : mesothel and endthelial cells of blood vessel of sub-mesothelal

Plasminogen

Plasmin

FIBRIN
Lysis Process

Degradation product fibrin

Balance PA & PAI

PA

PAI

Increase fibrinolysis Prevent Adhesion

Cellular events of Adhesions

COLLAGEN PMN MACROPHAGES

FIBRIN

FIBROBLASTS CAPILLARIES

Pathophysiology

Fibrinolysis

Cited : Treutner KH (eds). Peritoneal Adhesions. Springer, Berlin, 1997.

Fibrinous Adhesion

Healing without adhesion

Permanent adhesion

Why does adhesion cause problems ?

Effect on patients :
Cost on adhesiolysis : US$ 1.3 miliar (Ray, 1998) Infertility (15-20%) Chronic Abdominal & pelvic pain ( 20 - 50 %) Lower quality of life Loss of work days & productivity (Ray, 1998) Higher operation risks (Opelka, 1998)

Why does adhesion cause problems ?

Effect on surgeons :
Higher risk of enterotomy

Longer operating time (relaparotomy)

Increase the intensity of surgery

Frank Opelka, 1998

Why does adhesion cause problems ?

Effects on health care system :

Cost of hospital care : US $ 1.33 billion(1994) Adhesiolysis

$ 13.117, 20 )

846,415 hospitalization days (US 19% primary procedure.

adhesiolysis will result in 1-2 day increased of

hospitalization days (Ray , 1998)

Grading : Midline Adhesion Score (Opelka, 1998)

Mild: hand/blunt dissection Moderate: sharp dissection Severe: extensive sharp dissection Extreme:cause enterotomy

37% 24%

10% 29%

Prevention of adhesion formation

Surgical Strategies :
Careful tissue handling Carefull hemostasis Avoiding the drying peritoneal surfaces Asepsis Starch-gloves Non-linting swabs Avoidance of tissue schaemia

Many of these objectives can be better obtained through Meticulous surgical tehniques or Laparoscopy

Prevention of adhesion formation

Medical prevention
Anticoagulants
Heparin: Significantly caused hemorrhage and wound disruptions

Antiinflammatory agents
Corticosteroid Nonsteroidal : Ibuprofen, Ketorolac tromethamine

Progestin : Fibrinolytic Enzymes stimulating plasminogen activator: Antibiotics : Mechanical barriers : Interceed, Sepra film

Tasks

Discuss a patient with wound healing problems, e.g. :

Wound dehiscence Deep burn injury

Chronic ulcer

Teams : 1st resident, Fascilatator : related subdivision References : Greenfield, Scientific Basis of Surgery, & Surgery Basic Science & Clinical evidence (Norton, et all)

Problems to be discussed :

Case I: A patient with bladder carcinoma who underwent Cystectomy + ileal conduit and developed post-operative complications :
Ileal anastomotic leakage

Uretero-ileal conduit leakage

Wound dehiscence

Issues :
Factors influencing wound healing, including uremia Regulation of wound healing phases Role of nutrition in wound healing

Problems to be discussed :

Case II:
Excessive scarring :

Etiology ? Predisposing factors : why in the regions with greater tension ? What is the role of granulation tissues in wound healing process ?