- •Preface and Acknowledgments
- •Contents
- •Contributors
- •1: Embryology for Urologists
- •Introduction
- •Renal Development
- •Pronephros
- •Mesonephros
- •Metanephros
- •Development of the Collecting System
- •Critical Steps in Further Development
- •Anomalies of the Kidney
- •Renal Agenesis
- •Renal Aplasia
- •Renal Hypoplasia
- •Renal Ectopia
- •Renal Fusion
- •Ureteral Development
- •Anomalies of Origin
- •Anomalies of Number
- •Incomplete Ureteral Duplication
- •Complete Ureteral Duplication
- •Ureteral Ectopia
- •Embryology of Ectopia
- •Clinical Correlation
- •Location of Ectopic Ureteral Orifices – Male (in Descending Order According to Incidence)
- •Symptoms
- •Ureteroceles
- •Congenital Ureteral Obstruction
- •Pipestem Ureter
- •Megaureter-Megacystis Syndrome
- •Prune Belly Syndrome
- •Vascular Ureteral Obstructions
- •Division of the Urogenital Sinus
- •Bladder Development
- •Urachal Anomalies
- •Cloacal Duct Anomalies
- •Other Bladder Anomalies
- •Bladder Diverticula
- •Bladder Extrophy
- •Gonadal Development
- •Testicular Differentiation
- •Ovarian Differentiation
- •Gonadal Anomalies
- •Genital Duct System
- •Disorders of Testicular Function
- •Female Ductal Development
- •Prostatic Urethral Valves
- •Gonadal Duct Anomalies
- •External Genital Development
- •Male External Genital Development
- •Female External Genital Development
- •Anomalies of the External Genitalia
- •References
- •2: Gross and Laparoscopic Anatomy of the Upper Urinary Tract and Retroperitoneum
- •Overview
- •The Kidneys
- •The Renal Vasculature
- •The Renal Collecting System
- •The Ureters
- •Retroperitoneal Lymphatics
- •Retroperitoneal Nerves
- •The Adrenal Glands
- •References
- •3: Gross and Laparoscopic Anatomy of the Lower Urinary Tract and Pelvis
- •Introduction
- •Female Pelvis
- •Male Pelvis
- •Pelvic Floor
- •Urinary Bladder
- •Urethra
- •Male Urethra
- •Female Urethra
- •Sphincter Mechanisms
- •The Bladder Neck Component
- •The Urethral Wall Component
- •The External Urethral Sphincter
- •Summary
- •References
- •4: Anatomy of the Male Reproductive System
- •Testis and Scrotum
- •Spermatogenesis
- •Hormonal Regulation of Spermatogenesis
- •Genetic Regulation of Spermatogenesis
- •Epididymis and Ductus Deferens
- •Accessory Sex Glands
- •Prostate
- •Seminal Vesicles
- •Bulbourethral Glands
- •Penis
- •Erection and Ejaculation
- •References
- •5: Imaging of the Upper Tracts
- •Anatomy of the Upper Tracts and Introduction to Imaging Modalities
- •Introduction
- •Renal Upper Tract Basic Anatomy
- •Modalities Used for Imaging the Upper Tracts
- •Ultrasound
- •Radiation Issues
- •Contrast Issues
- •Renal and Upper Tract Tumors
- •Benign Renal Tumors
- •Transitional Cell Carcinoma
- •Renal Mass Biopsy
- •Renal Stone Disease
- •Ultrasound
- •Plain Radiographs and IVU
- •Renal Cystic Disease
- •Benign Renal Cysts
- •Hereditary Renal Cystic Disease
- •Complex Renal Cysts
- •Renal Trauma
- •References
- •Introduction
- •Pathophysiology
- •Susceptibility and Resistance
- •Epidemiological Breakpoints
- •Clinical Breakpoints
- •Pharmacodynamic Parameters
- •Pharmacokinetic Parameters
- •Fosfomycin
- •Nitrofurantoin
- •Pivmecillinam
- •b-Lactam-Antibiotics
- •Penicillins
- •Cephalosporins
- •Carbapenems
- •Aminoglycosides
- •Fluoroquinolones
- •Trimethoprim, Cotrimoxazole
- •Glycopeptides
- •Linezolid
- •Conclusion
- •References
- •7: An Overview of Renal Physiology
- •Introduction
- •Body Fluid Compartments
- •Regulation of Potassium Balance
- •Regulation of Acid–Base Balance
- •Diuretics
- •Suggested Reading
- •8: Ureteral Physiology and Pharmacology
- •Ureteral Anatomy
- •Modulation of Peristalsis
- •Ureteral Pharmacology
- •Conclusion
- •References
- •Introduction
- •Afferent Signaling Pathways
- •Efferent Signaling
- •Parasympathetic Nerves
- •Sympathetic Nerves
- •Vesico-Spinal-Vesical Micturition Reflex
- •Peripheral Targets
- •Afferent Signaling Mechanisms
- •Urothelium
- •Myocytes
- •Cholinergic Receptors
- •Muscarinic Receptors
- •Nicotinic Receptors
- •Adrenergic Receptors (ARs)
- •a-Adrenoceptors
- •b-Adrenoceptors
- •Transient Receptor Potential (TRP) Receptors
- •Phosphodiesterases (PDEs)
- •CNS Targets
- •Opioid Receptors
- •Serotonin (5-HT) Mechanisms
- •g-Amino Butyric Acid (GABA) Mechanisms
- •Gabapentin
- •Neurokinin and Neurokinin Receptors
- •Summary
- •References
- •10: Pharmacology of Sexual Function
- •Introduction
- •Sexual Desire/Arousal
- •Endocrinology
- •Steroids in the Male
- •Steroids in the Female
- •Neurohormones
- •Neurotransmitters
- •Dopamine
- •Serotonin
- •Pharmacological Strategies
- •CNS Drugs
- •Enzyme-inducing Antiepileptic Drugs
- •Erectile Function
- •Ejaculatory Function
- •Premature Ejaculation
- •Abnormal Ejaculation
- •Conclusions
- •References
- •Epidemiology
- •Calcium-Based Urolithiasis
- •Uric Acid Urolithiasis
- •Infectious Urolithiasis
- •Cystine-Based Urolithiasis
- •Aims
- •Who Deserves Metabolic Evaluation?
- •Metabolic Workup for Stone Producers
- •Medical History and Physical Examination
- •Stone Analysis
- •Serum Chemistry
- •Urine Evaluation
- •Urine Cultures
- •Urinalysis
- •Twenty-Four Hour Urine Collections
- •Radiologic Imaging
- •Medical Management
- •Conservative Management
- •Increased Fluid Intake
- •Citrus Juices
- •Dietary Restrictions
- •Restricted Oxalate Diet
- •Conservative Measures
- •Selective Medical Therapy
- •Absorptive Hypercalciuria
- •Thiazide
- •Orthophosphate
- •Renal Hypercalciuria
- •Primary Hyperparathyroidism
- •Hyperuricosuric Calcium Oxalate Nephrolithiasis
- •Enteric Hyperoxaluria
- •Hypocitraturic Calcium Oxalate Nephrolithiasis
- •Distal Renal Tubular Acidosis
- •Chronic Diarrheal States
- •Thiazide-Induced Hypocitraturia
- •Idiopathic Hypocitraturic Calcium Oxalate Nephrolithiasis
- •Hypomagnesiuric Calcium Nephrolithiasis
- •Gouty Diathesis
- •Cystinuria
- •Infection Lithiasis
- •Summary
- •References
- •12: Molecular Biology for Urologists
- •Introduction
- •Inherited Changes in Cancer Cells
- •VEGR and Cell Signaling
- •Targeting mTOR
- •Conclusion
- •References
- •13: Chemotherapeutic Agents for Urologic Oncology
- •Introduction
- •Bladder Cancer
- •Muscle Invasive Bladder Cancer
- •Metastatic Bladder Cancer
- •Conclusion
- •Prostate Cancer
- •Other Chemotherapeutic Drugs or Combinations for Treating HRPC
- •Conclusion
- •Renal Cell Carcinoma
- •Chemotherapy
- •Immunotherapy
- •Angiogenesis Inhibitor Drugs
- •Conclusion
- •Testicular Cancer
- •Stage I Seminoma
- •Stage I non-seminomatous Germ Cell Tumours (NSGCT)
- •Metastatic Germ Cell Tumours
- •Low-Volume Metastatic Disease (Stage II A/B)
- •Advanced Metastatic Disease
- •Salvage Chemotherapy for Relapsed or Refractory Disease
- •Conclusion
- •Penile Cancer
- •Side Effects of Chemotherapy
- •Conclusion
- •References
- •14: Tumor and Transplant Immunology
- •Antibodies
- •Cytotoxic and T-helper Cells
- •Immunosuppression
- •Induction Therapy
- •Maintenance Therapy
- •Rejection
- •Posttransplant Lymphoproliferative Disease
- •Summary
- •References
- •15: Pathophysiology of Renal Obstruction
- •Causes of Renal Obstruction
- •Effects on Prenatal Development
- •Prenatal Hydronephrosis
- •Spectrum of Renal Abnormalities
- •Renal Functional Changes
- •Renal Growth/Counterbalance
- •Vascular Changes
- •Inflammatory Mediators
- •Glomerular Development Changes
- •Mechanical Stretch of Renal Tubules
- •Unilateral Versus Bilateral
- •Limitations of Animal Models
- •Future Research
- •Issues in Patient Management
- •Diagnostic Imaging
- •Ultrasound
- •Intravenous Urography
- •Antegrade Urography and the Whitaker Test
- •Nuclear Renography
- •Computed Tomography
- •Magnetic Resonance Urography
- •Hypertension
- •Postobstructive Diuresis
- •References
- •Introduction
- •The Normal Lower Urinary Tract
- •Anatomy
- •Storage Function
- •Voiding Function
- •Neural Control
- •Symptoms
- •Flow Rate and Post-void Residual
- •Voiding Cystometry
- •Male
- •Female
- •Neurourology
- •Conclusions
- •References
- •17: Urologic Endocrinology
- •The Testis
- •Normal Androgen Metabolism
- •Epidemiological Aspects
- •Prostate
- •Brain
- •Muscle Mass and Adipose Tissue
- •Bones
- •Ematopoiesis
- •Metabolism
- •Cardiovascular System
- •Clinical Assessment
- •Biochemical Assessment
- •Treatment Modalities
- •Oral Preparations
- •Parenteral Preparations
- •Transdermal Preparations
- •Side Effects and Treatment Monitoring
- •Body Composition
- •Cognitive Decline
- •Bone Metabolism
- •The Kidneys
- •Endocrine Functions of the Kidney
- •Erythropoietin
- •Calcitriol
- •Renin
- •Paraneoplastic Syndromes
- •Hypercalcemia
- •Hypertension
- •Polycythemia
- •Other Endocrine Abnormalities
- •References
- •General Physiology
- •Prostate Innervation
- •Summary
- •References
- •Wound Healing
- •Inflammation
- •Proliferation
- •Remodeling
- •Principles of Plastic Surgery
- •Tissue Characteristics
- •Grafts
- •Flap
- •References
- •Lower Urinary Tract Symptoms
- •Storage Phase
- •Voiding Phase
- •Return to Storage Phase
- •Urodynamic Parameters
- •Urodynamic Techniques
- •Volume Voided Charts
- •Pad Testing
- •Typical Test Schedule
- •Uroflowmetry
- •Post Voiding Residual
- •Further Diagnostic Evaluation of Patients
- •Cystometry with or Without Video
- •Cystometry
- •Videocystometrography (Cystometry + Cystourethrography)
- •Cystometric Findings
- •Comment:
- •Measurements During the Storage Phase:
- •Measurements During the Voiding Phase:
- •Abnormal Function
- •Disorders of Sensation
- •Causes of Hypersensitive Bladder Sensation
- •Causes of Hyposensitive Bladder Sensation
- •Disorders of Detrusor Motor Function
- •Bladder Outflow Tract Dysfunction
- •Detrusor–Urethral Dyssynergia
- •Detrusor–Bladder Neck Dyssynergia
- •Detrusor–Sphincter Dyssynergia
- •Complex Urodynamic Investigation
- •Urethral Pressure Measurement
- •Technique
- •Neurophysiological Evaluation
- •Conclusion
- •References
- •Endoscopy
- •Cystourethroscopy
- •Ureteroscopy and Ureteropyeloscopy
- •Nephroscopy
- •Virtual Reality Simulators
- •Lasers
- •Clinical Application of Lasers
- •Condylomata Acuminata
- •Urolithiasis
- •Benign Prostatic Hyperplasia
- •Ureteral and Urethral Strictures
- •Conclusion
- •References
- •Introduction
- •The Prostatitis Syndromes
- •The Scope of the Problem
- •Category III CP/CPPS
- •The Goal of Treatment
- •Conservative Management
- •Drug Therapy
- •Antibiotics
- •Anti-inflammatories
- •Alpha blockers
- •Hormone Therapies
- •Phytotherapies
- •Analgesics, muscle relaxants and neuromodulators
- •Surgery
- •A Practical Management Plan
- •References
- •Orchitis
- •Definition and Etiology
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation
- •Treatment of Infectious Orchitis
- •Epididymitis
- •Definition and Etiology
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation of Epididymitis
- •Treatment of Acute Epididymitis
- •Treatment of Chronic Epididymitis
- •Treatment of Spermatic Cord Torsion
- •Fournier’s Gangrene
- •Definition and Etiology
- •Risk Factors
- •Clinical Signs and Symptoms
- •Diagnostic Evaluation
- •Treatment
- •References
- •Fungal Infections
- •Candidiasis
- •Aspergillosis
- •Cryptococcosis
- •Blastomycosis
- •Coccidioidomycosis
- •Histoplasmosis
- •Radiographic Findings
- •Treatment
- •Tuberculosis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Schistosomiasis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Filariasis
- •Clinical Manifestations
- •Diagnosis
- •Treatment
- •Onchocerciasis
- •References
- •25: Sexually Transmitted Infections
- •Introduction
- •STIs Associated with Genital Ulcers
- •Herpes Simplex Virus
- •Diagnosis
- •Treatment
- •Chancroid
- •Diagnosis
- •Treatment
- •Syphilis
- •Diagnosis
- •Treatment
- •Lymphogranuloma Venereum
- •Diagnosis
- •Treatment
- •Chlamydia
- •Diagnosis
- •Treatment
- •Gonorrhea
- •Diagnosis
- •Treatment
- •Trichomoniasis
- •Diagnosis
- •Treatment
- •Human Papilloma Virus
- •Diagnosis
- •Treatment
- •Scabies
- •Diagnosis
- •Treatment
- •References
- •26: Hematuria: Evaluation and Management
- •Introduction
- •Classification of Hematuria
- •Macroscopic Hematuria
- •Microscopic Hematuria
- •Dipstick Hematuria
- •Pseudohematuria
- •Factitious Hematuria
- •Menstruation
- •Aetiology
- •Malignancy
- •Urinary Calculi
- •Infection and Inflammation
- •Benign Prostatic Hyperplasia
- •Trauma
- •Drugs
- •Nephrological Causes
- •Assessment
- •History
- •Examination
- •Investigations
- •Dipstick Urinalysis
- •Cytology
- •Molecular Tests
- •Blood Tests
- •Flexible Cystoscopy
- •Upper Urinary Tract Evaluation
- •Renal USS
- •KUB Abdominal X-Ray
- •Intravenous Urography (IVU)
- •Computed Tomography (CT)
- •Retrograde Urogram Studies
- •Magnetic Resonance Imaging (MRI)
- •Additional Tests and Renal Biopsy
- •Intractable Hematuria
- •Loin Pain Hematuria Syndrome
- •References
- •27: Benign Prostatic Hyperplasia (BPH)
- •Historical Background
- •Pathophysiology
- •Patient Assessment
- •Treatment of BPH
- •Watchful Waiting
- •Drug Therapy
- •Interventional Therapies
- •Conclusions
- •References
- •28: Practical Guidelines for the Treatment of Erectile Dysfunction and Peyronie´s Disease
- •Erectile Dysfunction
- •Introduction
- •Diagnosis
- •Basic Evaluation
- •Cardiovascular System and Sexual Activity
- •Optional Tests
- •Treatment
- •Medical Treatment
- •Oral Agents
- •Phosphodiesterase Type 5 (PDE 5) Inhibitors
- •Nonresponders to PDE5 Inhibitors
- •Apomorphine SL
- •Yohimbine
- •Intracavernosal and Intraurethral Therapy
- •Intracavernosal Injection (ICI) Therapy
- •Intraurethral Therapy
- •Vacuum Constriction Devices
- •Surgical Therapy
- •Conclusion
- •Peyronie´s Disease (PD)
- •Introduction
- •Oral Drug Therapy
- •Intralesional Drug Therapy
- •Iontophoresis
- •Radiation Therapy
- •Surgical Therapy
- •References
- •29: Premature Ejaculation
- •Introduction
- •Epidemiology
- •Defining Premature Ejaculation
- •Voluntary Control
- •Sexual Satisfaction
- •Distress
- •Psychosexual Counseling
- •Pharmacological Treatment
- •On-Demand Treatment with Tramadol
- •Topical Anesthetics
- •Phosphodiesterase Inhibitors
- •Surgery
- •Conclusion
- •References
- •30: The Role of Interventional Management for Urinary Tract Calculi
- •Contraindications to ESWL
- •Complications of ESWL
- •PCNL Access
- •Instrumentation for PCNL
- •Nephrostomy Drains Post PCNL
- •Contraindications to PCNL
- •Complications of PCNL
- •Semirigid Ureteroscopy
- •Flexible Ureteroscopy
- •Electrohydraulic Lithotripsy (EHL)
- •Ultrasound
- •Ballistic Lithotripsy
- •Laser Lithotripsy
- •Ureteric Stents
- •Staghorn Calculi
- •Lower Pole Stones
- •Horseshoe Kidneys and Stones
- •Calyceal Diverticula Stones
- •Stones and PUJ Obstruction
- •Treatment of Ureteric Colic
- •Medical Expulsive Therapy (MET)
- •Intervention for Ureteric Stones
- •Stones in Pregnancy
- •Morbid Obesity
- •References
- •Anatomy and Function
- •Pathophysiology
- •Management
- •Optical Urethrotomy/Dilatation
- •Urethral Stents
- •Preoperative Assessment
- •Urethroplasty
- •Anastomotic Urethroplasty
- •Substitution Urethroplasty
- •Grafts Versus Flaps
- •Oral Mucosal Grafts
- •Tissue Engineering
- •Graft Position
- •Conclusion
- •References
- •32: Urinary Incontinence
- •Epidemiology and Risk Factors
- •Pathophysiology
- •Urge Incontinence
- •Conservative Treatments
- •Pharmacotherapy
- •Invasive/ Surgical Therapies
- •Stress Urinary Incontinence
- •Male SUI Therapies
- •Female SUI Therapies
- •Mixed Urinary Incontinence
- •Conclusions
- •References
- •33: Neurogenic Bladder
- •Introduction
- •Examination and Diagnostic Tests
- •History and Physical Examination
- •Imaging
- •Urodynamics (UDS)
- •Evoked Potentials
- •Classifications
- •Somatic Pathways
- •Brain Lesions
- •Cerebrovascular Accident (CVA)
- •Parkinson’s Disease (PD)
- •Multiple Sclerosis
- •Huntington’s Disease
- •Dementias
- •Normal Pressure Hydrocephalus (NPH)
- •Tumors
- •Psychiatric Disorders
- •Spinal Lesions and Pathology
- •Intervertebral Disk Prolapse
- •Spinal Cord Injury (SCI)
- •Transverse Myelitis
- •Peripheral Neuropathies
- •Metabolic Neuropathies
- •Pelvic Surgery
- •Treatment
- •Summary
- •References
- •34: Pelvic Prolapse
- •Introduction
- •Epidemiology
- •Anatomy and Pathophysiology
- •Evaluation and Diagnosis
- •Outcome Measures
- •Imaging
- •Urodynamics
- •Indications for Management
- •Biosynthetics
- •Surgical Management
- •Anterior Compartment Repair
- •Uterine/Apical Prolapse
- •Enterocele Repair
- •Conclusion
- •References
- •35: Urinary Tract Fistula
- •Introduction
- •Urogynecologic Fistula
- •Vesicovaginal Fistula
- •Etiology and Risk Factors
- •Clinical Factors
- •Evaluation and Diagnosis
- •Pelvic Examination
- •Cystoscopy
- •Imaging
- •Treatment
- •Conservative Management
- •Surgical Management
- •Urethrovaginal Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Ureterovaginal Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Vesicouterine Fistula
- •Etiology and Presentation
- •Diagnosis and Management
- •Uro-Enteric Fistula
- •Vesicoenteric Fistula
- •Pyeloenteric Fistula
- •Urethrorectal Fistula
- •References
- •36: Urologic Trauma
- •Introduction
- •Kidney
- •Expectant Management
- •Endovascular Therapy
- •Operative Intervention
- •Operative Management: Follow-up
- •Reno-Vascular Injuries
- •Pediatric Renal Injuries
- •Adrenal
- •Ureter
- •Diagnosis
- •Treatment
- •Delayed Diagnosis
- •Bladder and Posterior Urethra
- •Bladder Injuries: Initial Management
- •Bladder Injuries: Formal Repair
- •Anterior Urethral Trauma
- •Fractured Penis
- •Penile Amputation
- •Scrotal and Testicular Trauma
- •Imaging
- •CT-IVP (CT with Delayed Images)
- •Technique
- •Cystogram
- •Technique
- •Retrograde Urethrogram (RUG)
- •Technique
- •Retrograde Pyelogram (RPG)
- •Technique
- •One-Shot IVP
- •Technique
- •References
- •37: Bladder Cancer
- •Who Should Be Investigated?
- •Epidemiology
- •Risk Factors
- •Role of Screening
- •Signs and Symptoms
- •Imaging
- •Cystoscopy
- •Urine Tests
- •PDD-Assisted TUR
- •Pathology
- •NMIBC and Risk Groups
- •Intravesical Chemotherapy
- •Intravesical Immunotherapy
- •Immediate Cystectomy and CIS
- •Radical Cystectomy with Pelvic Lymph Node Dissection
- •sexual function-preserving techniques
- •Bladder-Preservation Treatments
- •Neoadjuvant Chemotherapy
- •Adjuvant Chemotherapy
- •Preoperative Radiotherapy
- •Follow-up After TUR in NMIBC
- •References
- •38: Prostate Cancer
- •Introduction
- •Epidemiology
- •Race
- •Geographic Variation
- •Risk Factors and Prevention
- •Family History
- •Diet and Lifestyle
- •Prevention
- •Screening and Diagnosis
- •Current Screening Recommendations
- •Biopsy
- •Pathology
- •Prognosis
- •Treatment of Prostate Cancer
- •Treatment for Localized Prostate Cancer (T1, T2)
- •Radical Prostatectomy
- •EBRT
- •IMRT
- •Brachytherapy
- •Treatment for Locally Advanced Prostate Cancer (T3, T4)
- •EBRT with ADT
- •Radical Prostatectomy
- •Androgen-Deprivation Therapy
- •Summary
- •References
- •39: The Management of Testis Cancer
- •Presentation and Diagnosis
- •Serum Tumor Markers
- •Primary Surgery
- •Testis Preserving Surgery
- •Risk Stratification
- •Surveillance Versus Primary RPLND
- •Primary RPLND
- •Adjuvant Treatment for High Risk
- •Clinical Stage 1 Seminoma
- •Risk-Stratified Adjuvant Treatment
- •Adjuvant Radiotherapy
- •Adjuvant Low Dose Chemotherapy
- •Primary Combination Chemotherapy
- •Late Toxicity
- •Salvage Strategies
- •Conclusion
- •References
- •Index
19
Wound Healing and Principles of
Plastic Surgery
Timothy O. Davies and Gerald H. Jordan
Wound Healing
Wound healing is the natural restorative response to tissue injury. Essential to optimizing surgical procedures and evolving novel techniques, a basic understanding of the basic principles of wound healing is necessary. Types of wound closure are classified as primary, secondary, and tertiary. Primary wound healing refers to those wounds which are immediately closed with direct epithelial/mucosal approximation. Secondary wound healing refers to those wounds that all or a portion are left open to heal, without any attempt at closure. These will heal by granulation, reepithelialization, and wound contraction. Tertiary wound healing refers to wounds closed by delayed primary closure.
The process of wound healing is usually described in three phases: inflammation, proliferation, and remodeling. The inflammatory phase is initiated immediately at the time of injury and consists of hemostasis and debridement of the wound by inflammatory cells. The events of the proliferative phase include epithelialization, fibroplasia, and angiogenesis. The remodeling phase strengthens the wound by reorganizing collagen to increase tensile strength.
Inflammation
Hemostasis and sealing the wound are the first steps to repairing an injury. The release
of epinephrine and norepinephrine, as well as prostaglandins, mediates initial local vasoconstriction.The exposure of collagen (types 4 and 5) and basement membrane proteins from endothelial cells activate platelet aggregation and the coagulation pathway, both intrinsic and extrinsic clotting factors.1 With the initiation of the clotting cascade, the eventual product – thrombin – catalyzes fibrinogen to fibrin. Fibrin traps red blood cells and clotting ensues to seal the wound. This initial clot is primarily composed of aggregated platelets and fibrin.
Platelets are activated by adherence to exposed collagen and respond with the release of stored factors in alpha granules (storage organelles) and dense bodies. The alpha granules release platelet-derived growth factor (PDGF), transforming growth factor b (TGF-b), fibrinogen, and other vasoactive and chemotatic substances when they degrade. These substances further stimulate platelet aggregation, vasodilation, and increased vascular permeability.2 The action of phospholipases on disrupted cell membranes causes arachidonic acid release. This results in thromboxane and prostaglandin accumulation in injured tissue promoting further platelet aggregation and vasoconstriction.
The initial vasoconstriction is followed by vasodilation mediated by PDGF, TGF-b, and other vasoactive factors. Vasodilation and increased vascular permeability are also mediated by histamine and endothelial growth factor (EGF). These cytokines are released by injured endothelial cells and local mast cells.3
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the typical erythema that accompanies acute |
Wound healing events during this phase of |
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injury.With the release of these chemotatic sub- |
wound healing include mesenchymal cell |
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stances, leukocytes (neutrophils, monocytes, |
chemotaxis and proliferation (fibroplasia), |
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macrophages, and lymphocytes) are drawn into |
angiogenesis, and epithelialization.9 This phase |
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the wound. |
of wound healing begins with a provisional |
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Neutrophils phagocytize necrotic debris, for- |
matrix of fibrin and fibronectin being formed. |
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eign material, and bacteria.4 They are the domi- |
The matrix consists of a papillary bed, fibro- |
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nant white blood cell early in wound healing. |
blasts, macrophages, and a loose arrangement of |
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After phagocytosis and digestion, neutrophils |
collagen, fibronectin, and bacteria. Macrophages |
|
either die (releasing free oxygen radicals and |
are the principal cell in the initial matrix; how- |
|
destructive enzymes) or are engulfed by mac- |
ever, fibroblasts quickly increase in numbers |
|
rophages.5 The release of free oxygen radicals |
during this phase of healing. Fibroblasts are |
|
and enzymes by the destruction of neutrophils |
normally located in the dermis and are often |
|
can prolong the inflammatory reaction (oxi- |
damaged by the initial insult. Fibroblasts, medi- |
|
dizing stress). Areas of encapsulated chronic |
ated by cytokines, quickly become the most |
|
inflammation, which are termed granulomas, |
dominant cell in the proliferative phase. PDGF, |
|
may develop as a result of ongoing release of |
fibronectin, and EGF are chemotactic for both |
|
these enzymes and subsequent continued gen- |
fibroblasts and smooth muscle cells.10 |
|
eration of free oxygen radicals. The recruitment |
Fibroblasts divide and produce the compo- |
|
of macrophages to safely remove neutro- |
nents of the extracellular matrix.8 The extracel- |
|
phils from a wound may help prevent chronic |
lular matrix contains collagen, proteoglycans, |
|
inflammation. |
and attachment proteins such as fibronectin. |
|
Macrophages are central to wound healing.6 |
Over this phase,the amount of collagen increases |
|
Following the first 24–48 h, they become the |
to become the primary structural element in the |
|
prevailing white blood cells in the wound. As a |
wound matrix. Collagen is synthesized pri- |
|
response to chemotatic agents (like TGF-b), cir- |
marily by fibroblasts in a complex process that |
|
culating monocytes and tissue macrophages |
begins 3–5 days after injury.11 Procollagen, the |
|
migrate to the wound. They engulf necrotic tis- |
precursor of collagen is formed within fibro- |
|
sue and bacteria as well as remove the remain- |
blasts and released.It is composed of long chains |
|
ing neutrophils preventing ongoing release of |
which are linked together in a helical configura- |
|
inflammatory mediators. Additionally, mac- |
tion and cleaved by proteases to form collagen.12 |
|
rophages release many different growth factors |
TGF-b increases collagen synthesis and gluco- |
|
and cytokines. This allows for fibroblast prolif- |
corticoids interfere with wound healing during |
|
eration, angiogenesis, extracellular matrix pro- |
this step by decreasing collagen synthesis. As |
|
duction, and the recruitment of additional |
collagen matures, cross-linking occurs between |
|
leukocytes. For example, Interleukin-1 (IL-1) is |
chains of collagen to form larger collagen fibrils. |
|
secreted by macrophages, causing lymphocyte |
Vitamin C is a necessary nutrient in hydroxyla- |
|
activation and is chiefly responsible for the |
tion, which stabilizes and cross-links collagen. |
|
febrile response as a result of circulating IL-1 |
The increased cross-linking increases the tensile |
|
reaching the hypothalamus.7 Activated mono- |
strength of the wound. Collagen synthesis is |
|
cytes and macrophages stimulate collagen pro- |
dependent both on local oxygen and vascular |
|
duction and release matrix metalloproteinases |
supply. |
|
(MMPs) – including collagenases – aiding in |
Angiogenesis is stimulated by high lactate |
|
breaking down and repairing damaged tissue |
levels, an acidic pH, and decreased oxygen |
|
matrix. In order for there to be orderly progress |
tension in the tissue.9 Fibroblast growth fac- |
|
of wound healing, a balance between MMPs and |
tor (FGF) and vascular endothelial growth |
|
tissue inhibitory metalloproteinases (TIMPs) |
factor (VEGF) are important factors in angio- |
|
must exist.8 If not the effect of MMPs may extend |
genesis. The epithelial cells secrete VEGF in |
|
to adjacent uninjured tissues. Repair of the |
response to hypoxia signaling to fibroblasts to |
|
wound begins in the proliferative phase of |
stimulate angiogenesis. The subsequent rele- |
|
wound healing. |
ase of growth factors from the macrophages |
251
WoUnd HEaling and PrinciPlEs of Plastic sUrgEry
stimulates angiogenesis by proliferation and ingrowth of endothelial cells. These new endothelial cells stimulate neovascularization by the formation of capillaries.13 These new capillaries provide oxygen and nutrients to support ongoing proliferation. Local oxygenation can be impeded by atherosclerosis, local small vessel disease, and preexisting scarring. Edema, which is sequestered extracellular fluid, inhibits wound healing by increasing the diffusion distance of oxygen from its target. Local oxygenation can be augmented with the use of hyperbaric oxygen, although the frequency and duration of such treatment is not fully elucidated.14
Regeneration of the epithelium is important |
|
|
to seal the wound and prevent further water loss. |
|
|
The two layers of the skin are the epidermis and |
|
|
the dermis. The epidermis is multilayered. The |
|
|
stratum corneum, the most superficial layer of |
|
|
epidermis, consists primarily of dead cells and |
|
|
keratin. The deeper epidermal layer is composed |
|
|
of a protective layer of the skin which provides |
|
|
protection from water loss. The dermis too is |
|
|
multilayered, consisting of a superficial layer, |
|
|
the periadnexal in areas where adnexal struc- |
|
|
tures are absent, and the deep or reticular layer |
Figure 19.1. cross-section of the skin (reprinted with permis- |
|
containing the majority of collagen content and |
||
the lymphatics (Fig. 19.1). |
sion from Jordan and Mccraw15.copyright © american Urological |
|
association Education and research, inc). |
||
The first step in epithelialization is the for- |
||
|
||
mation of the clot to seal the wound. This pro- |
being anchored to dermis, epithelial cells pro- |
|
tects against bacterial invasion as well as |
||
prevents fluid loss. Initially, the epithelial cells |
vide little strength. |
|
migrate across the wound and can completely |
The definition of wound contraction is the |
|
cover a surgically coapted wound in 18–24 h. 14 |
movement of tissue toward the center of the |
|
Epithelial cells migrate from epithelium. This |
wound. This should not be confused with wound |
|
can be from the wound edge or in partial thick- |
contracture,which is physically constrained joint |
|
ness wounds – from epithelial appendages |
motion as a result of wound contraction. Wound |
|
(e.g., hair follicles, sweat and sebaceous |
contraction typically begins 4–5 days after injury |
|
glands). As epithelial cells cross the wound and |
and will continue for 12–15 days.9 The rate of |
|
contact each other, the speed of migration |
movement varies by the type of tissue and how |
|
slows and is stopped by contact inhibition. |
much laxity exists at the point of contraction. |
|
Epithelial cell migration is decreased by bacte- |
Contraction is mediated by fibroblasts and myo- |
|
ria, large amounts of exudate, and necrotic |
fibroblasts, which act similarly to smooth muscle |
|
tissue. Reestablishment of a mature epithelial |
cells. Pharmaceuticals (e.g., colchicine) that |
|
layer is an important component of scar reso- |
inhibit microtubules (tubulin) minimize wound |
|
lution. In full thickness injuries, epithelializa- |
contraction implicating the important role of |
|
tion occurs from the edge of the wound at a |
microtubules in this phase of wound healing. |
|
rate of 1–2 mm per day.14 Regenerated epithe- |
The process of wound contraction requires cell |
|
lium does not retain all the features of normal |
division and is inhibited by local radiation and |
|
epithelium. It has fewer basal cells and the |
systemic chemotherapy drugs. |
|
interface between dermis and epidermis is |
In those areas with more elastic skin wounds, |
|
abnormal as rete pegs are absent. Without |
wound contraction can be augmented greatly by |