Obat Luka Operasi Caesar

By obatherbalkanker - Last updated: Thursday, June 9, 2011 - Save & Share - Leave a Comment

Operasi Caesar ini dianjurkan untuk proses kelahiran yang sulit, seperti: ketika si bayi dalam kandungan dalam posisi sungsang atau terlilit tali pusar atau ukuran bayi terlalu besar, juga ketika si ibu ternyata tidak cukup kuat untuk melahirkan dan atau punya masalah dengan kesehatannya. Namun, dewasa ini, ternyata Operasi Caesar tidak melulu hanya diperuntukkan untuk kelahiran sulit seperti di atas, banyak para ibu yang lebih memilih melahirkan secara Operasi Caesar dengan alasan, seperti : takut / fobia terhadap proses persalinan, takut terhadap rasa nyeri yang diakibatkan selama masa persalinan, bahkan juga dengan alasan ingin melahirkan pada hari-tanggal-waktu yang ditentukannya sendiri (tentu saja itu tidak masalah, asalkan si bayi dalam kandungan memang telah cukup umur). Memang melahirkan bayi dengan cara Operasi Caesar lebih cepat dan mudah, si ibu tidak usah bercapek-capek atau bersakit-sakit. Namun, bukan berarti Operasi Caesar tidak bercela. Dari hasil riset para dokter di dunia menunjukkan, bahwa melahirkan secara Operasi Caesar akan memerlukan waktu penyembuhan luka rahim yang lebih lama dari pada persalinan normal. Selama luka belum benar-benar sembuh, rasa nyeri bisa saja timbul pada luka tersebut. Bahkan menurut pengakuan para ibu yang melahirkannya menggunakan prosedur operasi, rasa nyeri memang kerap terasa sampai beberapa hari setelah operasi. Kami anjurkan agar para ibu yang habis dioperasi agar rajin check-up ke dokter untuk memastikan jahitan-jahitan benar telah tertutup dan tidak terjadi infeksi lanjutan. Ibu yang melahirkan bayi dengan Operasi Caesar juga dianjurkan untuk tidak mengandung kembali kurang dari 18 bulan dari tindakan Operasi Caesar, karena mempunyai resiko tinggi untuk terjadinya robekan rahim, seperti menurut analisa Dr. Thomas D. Shipp dari Sekolah Kedokteran Harvard di Boston Massachusetts, AS bersama rekan-rekannya. Menurut mereka, perempuan yang melahirkan kembali dalam kurun waktu 18 bulan setelah Operasi Caesar, kemungkinan rahimnya robek (ruptur uteri) adalah sebesar tiga kali lipat dibandingkan mereka yang menunggu lebih lama sebelum melahirkan kembali. Hal ini karena belum selesainya penyembuhan luka rahim karena Operasi Caesar pertama. Namun jangan khawatir sekarang ada Jelly Gamat Obat Luka Operasi Caesar yang membantu penyembuhan luka rahim setelah melakukan Operasi Caesar.

Berikut kisahnya : Kering Luka Caesar Karena Teripang : Sumber : trubus online : Senin, Juni 16, 2008 22:27:18 Perasaan berseberangan itu menghinggapi benak Suci Nurhayati. Ia bahagia ketika dokter menyatakan dirinya hamil anak ke-3. Namun, ia juga was-was bila melahirkan jabang bayi dengan Operasi Caesar seperti pada kelahiran anak sebelumnya. Ia ingat persis ketika melahirkan Alexander Wijaya Kusuma, anak keduanya pada 22 Desember 2001. Kepala sang jabang bayi terlilit tali pusar sehingga berakibat nyaris mati lemas. Pascaoperasi ia berharap dapat menjalani harihari seperti biasa sebagai karyawan di perusahaan otomotif dari Jerman. Namun, bekas Operasi Caesar yang membelah perutnya menyisakan nyeri berkepanjangan akibat bengkak dan lama mengering. Perubahan itu disertai siklus menstruasinya tak teratur. Berjalan di pusat perbelanjaan untuk membeli kebutuhan sehari-hari akan dirasakan sebagai sebuah siksaan. Sebab, kerap kali ia merasa lemas dan kakinya bengkak. Selain itu daya tahan tubuhnya lemah. Ia kerap mengalami flu, demam, dan mudah lelah. Ketika gangguan kesehatan itu belum pulih, dokter menyatakan ia hamil pada Maret 2005. Dua operasi

Kecemasannya terbukti. Dokter menyarankan agar ia menjalani Operasi Caesar untuk melahirkan anak ketiganya. Alasan dokter lantaran usia Suci cukup rawan untuk melahirkan secara normal. Perempuan kelahiran Kuningan, Jawa Barat, 17 Juli 1968 itu menuruti saran dokter. Saat pemeriksaan itu dokter menyatakan cara menutup bekas potongan kulit perut pada Operasi Caesar sebelumnya tidak rapi. Dampaknya luka lama mengering dan bengkak. Selain itu lemak dan varises menutupi rahim sehingga siklus menstruasinya terganggu. Oleh karena itu dokter yang membantu persalinan menawarkan 2 operasi sekaligus: Operasi Caesar ke-2 dan operasi membersihkan bekas operasi sebelumnya. Ia mengkombinasikan obat asal Tiongkok untuk mempercepat kesembuhan sekaligus obat yang diresepkan dokter. Namun, hingga 7 bulan luka bekas operasi itu tak kunjung pulih. Ia kerap merasa nyeri. Daya tahan tubuh juga acap anjlok, terbukti dengan tingginya frekuensi Suci menderita demam, flu, dan gampang lelah. Dalam kondisi luka belum pulih, ia hamil anak ke-4 pada Desember 2006. Pada kehamilan ke-4 itulah ia rutin mengkonsumsi 2 sendok makan ekstrak teripang setiap hari. Usianya 39 tahun ketika Suci menjalani Operasi Caesar yang ke-3. Ia menjalaninya dengan percaya diri. Konsumsi ekstrak teripang terus dilanjutkan setelah ia menjalani operasi. Hasilnya sungguh mengagumkan. Hanya sepekan pascaoperasi, luka bekas operasi mengering dan hampir tak berbekas. Ia juga merasa lebih fit dan daya tahan tubuhnya meningkat sehingga tetap bugar meski pekerjaan bertumpuk dan mengurusi keempat anaknya yang membutuhkan tenaga ekstra. Ekstrak teripang membantu menyembuhkan luka operasi? Menurut dr Zen Djaja MD, dokter di Malang, Jawa Timur, ekstrak namako-nama teripang di Jepang-baik diberikan kepada perempuan hamil. Itu lantaran senyawa aktif dan kandungan gizi teripang amat lengkap. Prof Zaiton Hassan, peneliti Departemen Ilmu Pangan Universitas Putra Malaysia mengatakan teripang mengandung asam miristat, palmitat, almitoleat, stearat, oleat, linoleat, arakhsidat,eicosapentaenat, behenat, erusat, dan docosahexaenat. Asam lemak itulah yang berperan terhadap pemulihan luka operasi. Kandungan asam eicosapentaenat (EPA) dan asam docosahexaenat (DHA) relatif tinggi, masing-masing 25,69% dan 3,69%. Tingginya kadar EPA menandakan kecepatan teripang memperbaiki jaringan rusak. Kandungan kolagen dalam ekstrak teripang mempercepat penyembuhan luka dalam dan luar setelah pembedahan seperti akibat Operasi Caesar yang dijalani Suci. Karena teripang cepat memulihkan daya tahan tubuh, makanya para nelayan di negeri jiran mengkonsumsinya sebelum melaut. Di lautan yang berombak ganas, daya tahan tubuh mereka tetap terjaga. Kondisi serupa dialami Suci yang 3 kali menjalani Operasi Caesar. Lukanya mengering hanya dalam sepekan. Padahal, luka 2 Operasi Caesar sebelumnya yang ia jalani baru sembuh setelah 7 bulan. (Faiz Yajri)

http://obatherbalkanker.com/obatherbaltradisional/obat-herbal-alami-jellygamat-gold-g-mempercepat-penyembuhan-luka-operasi-caesar ----------------------------------HUBUNGAN ANTARA STATUS GIZI PREOPERATIF DENGAN LAMA PENYEMBUHAN LUKA OPERASI PASIEN BEDAH DI RSUP Dr. KARIADI SEMARANG
Hersanti Sulistyaningrum, Hersanti Sulistyaningrum (2007) HUBUNGAN ANTARA STATUS GIZI PREOPERATIF DENGAN LAMA PENYEMBUHAN LUKA OPERASI PASIEN BEDAH DI RSUP Dr. KARIADI SEMARANG. Undergraduate thesis, Program Studi Ilmu Gizi .

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Abstract
Latar belakang : Status gizi preoperatif yang baik merupakan hal penting dalam penyembuhan luka luka operasi. Malnutrisi pada pasien bedah dapat mempengaruhi morbiditas karena terganggunya penyembuhan luka dan menurunnya daya tahan tubuh terhadap infeksi. Tujuan : Mengetahui hubungan antara status gizi preoperatif dengan lama penyembuhan luka operasi pasien bedah di RSUP Dr Kariadi Semarang. Metode : Penelitian ini adalah penelitian observasional dengan pendekatan cross sectional. Subjek merupakan pasien bedah ruang A3 RSUP Dr Kariadi Semarang yang menjalani operasi di bagian abdomen (operasi digestive dan urologi), berusia 18 sampai dengan 60 tahun, dan tidak menderita diabetes mellitus. Pengambilan sampel dilakukan dengan cara purposive pada bulan Januari hingga Februari 2007, berjumlah 24 orang. Status gizi dilihat dari pemeriksaan antropometri dengan cara menghitung Indeks Massa Tubuh (IMT) yaitu berat badan (kg)/tinggi badan (m)2 dan

pemeriksaan biokimia yaitu kadar serum albumin sampel yang dilihat dari catatan medik sampel. Data dianalisis dengan menggunakan uji Rank Spearman karena distribusi data tidak normal. Hasil : IMT subjek berkisar antara 14,44 kg/m2-25,20 kg/m2 dengan rerata:19,88 kg/m2 (SD 2,89). Kadar serum albumin subjek berkisar antara 2,6-5,0 gr/dl dengan rerata:3,45 gr/dl (SD 0,51). Lama penyembuhan luka operasi yang diderita subjek berkisar 5 - 14 hari dengan rerata 7 hari. Terdapat hubungan signifikan antara IMT dengan lama penyembuhan luka operasi dengan r = -0,421 dan p = 0,04. Selain itu hubungan antara kadar serum albumin dengan lama penyembuhan luka operasi juga signifikan dengan r = -0,501 dan p = 0,013. Simpulan : Ada hubungan signifikan antara status gizi subjek dengan lama penyembuhan luka operasi khususnya di bagian abdomen. Semakin baik IMT, semakin cepat penyembuhan luka operasi. Semakin tinggi albumin, semakin cepat penyembuhan luka operasi.

http://eprints.undip.ac.id/26131/

Obat Luka caesar

Kering Luka Caesar Karena Teripang : Simber : trubus online : Senin, Juni 16, 2008 22:27:18 Perasaan berseberangan itu menghinggapi benak Suci Nurhayati. Ia bahagia ketika dokter menyatakan dirinya hamil anak ke-3. Namun, ia juga waswas bila melahirkan jabangbayi dengan operasi caesar seperti pada kelahiran anak sebelumnya. Ia ingat persis ketika melahirkan Alexander Wijaya Kusuma, anak keduanya pada 22 Desember 2001. Kepala sang jabangbayi terlilit tali pusar sehingga berakibat nyaris mati lemas. Pascaoperasi ia berharap dapat menjalani hari-hari seperti biasa sebagai karyawan di perusahaan otomotif dari Jerman. Namun, bekas operasi caesar yang membelah perutnya menyisakan nyeri berkepanjangan akibat bengkak dan lama mengering. Perubahan itu disertai siklus menstruasinya tak teratur. Berjalan di pusat perbelanjaan untuk membeli kebutuhan sehari-hari akan dirasakan sebagai sebuah siksaan. Sebab, kerap kali ia merasa lemas dan kakinya bengkak. Selain itu daya tahan tubuhnya lemah. Ia kerap mengalami flu, demam, dan mudah lelah. Ketika gangguan kesehatan itu belum pulih, dokter menyatakan ia hamil pada Maret 2005. Dua operasi Kecemasannya terbukti. Dokter menyarankan agar ia menjalani operasi caesar untuk melahirkan anak ketiganya. Alasan dokter lantaran usia Suci cukup rawan untuk melahirkan secara normal. Perempuan kelahiran Kuningan, Jawa Barat, 17 Juli 1968 itu menuruti saran dokter. Saat pemeriksaan itu dokter menyatakan cara menutup bekas potongan kulit perut pada operasi caesar sebelumnya tidak rapi. Dampaknya luka lama mengering dan bengkak. Selain itu lemak dan varises menutupi rahim sehingga siklus menstruasinya terganggu. Oleh karena itu dokter yang membantu persalinan menawarkan 2 operasi sekaligus: operasi caesar ke-2 dan operasi membersihkan bekas operasi sebelumnya. Ia mengkombinasikan obat asal Tiongkok untuk mempercepat kesembuhan sekaligus obat yang diresepkan dokter. Namun, hingga 7 bulan luka bekas operasi itu tak kunjung pulih. Iakerap merasa nyeri. Daya tahan tubuh juga acap anjlok, terbukti dengan tingginya frekuensi Suci menderita demam, flu, dan gampang lelah. Dalam kondisi luka belum pulih, ia hamil anak ke-4 pada Desember 2006. Pada kehamilan ke-4 itulah ia rutin mengkonsumsi 2 sendok makan ekstrak teripang setiap hari. Usianya 39 tahun ketika Suci menjalani operasi caesar yang ke-3. Ia menjalaninya dengan percaya diri. Konsumsi ekstrak teripang terus dilanjutkan setelah ia menjalani operasi. Hasilnya sungguh mengagumkan. Hanya sepekan pascaoperasi, luka bekas operasi mengering dan hampir tak berbekas. Ia juga merasa lebih fit dan daya tahan tubuhnya meningkat sehingga tetap bugar meski pekerjaan bertumpuk dan mengurusi keempat anaknya yang membutuhkan tenaga ekstra. Ekstrak teripang membantu menyembuhkan luka operasi? Menurut dr Zen Djaja MD, dokter di Malang, Jawa Timur, ekstrak namako-nama teripang di Jepang-baik diberikan kepada perempuan hamil. Itu lantaran senyawa aktif dan kandungan gizi teripang amat lengkap. Prof Zaiton Hassan, peneliti Departemen Ilmu Pangan

Universitas Putra Malaysia mengatakan teripang mengandung asam miristat, palmitat, almitoleat, stearat, oleat, linoleat, arakhsidat,eicosapentaenat, behenat, erusat, dan docosahexaenat. Asam lemak itulah yang berperan terhadap pemulihan luka operasi. Kandungan asam eicosapentaenat (EPA) dan asam docosahexaenat (DHA) relatif tinggi, masing-masing 25,69% dan 3,69%. Tingginya kadar EPA menandakan kecepatan teripang memperbaiki jaringan rusak. Kandungan kolagen dalam ekstrak teripang mempercepat penyembuhan luka dalam dan luar setelah pembedahan seperti akibat operasi caesar yang dijalani Suci. Karena teripang cepat memulihkan daya tahan tubuh, makanya para nelayan di negeri jiran mengkonsumsinya sebelum melaut. Di lautanyang berombak ganas, daya tahan tubuh mereka tetap terjaga. Kondisi serupa dialami Suci yang 3 kali menjalani operasi caesar. Lukanya mengering hanya dalam sepekan. Padahal, luka 2 operasi caesar sebelumnya yang ia jalani baru sembuh setelah 7 bulan. (Faiz Yajri).

http://penyakit.biz/luka-caesar ------------------------------------------

Manfaat Protein Untuk Menyembuhkan Luka Operasi

Posted byAdmin on February 20, 2012 // Leave Your Comment
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Tahukah Anda, selain bermanfaat untuk membantu penyembuhan berbagai penyakit, protein juga bisa membantu menyembuhkan luka operasi. Protein merupakan faktor penting dalam setiap langkah penyembuhan luka. Tubuh bisa menyembuhkan luka dalam tiga tahap yaitu peradangan, kemudian pembentukan jaringan, lalu yang terakhir dengan remodeling kulit. Protein bekerja baik untuk merangsang dan mereproduksi kulit yang sehat dan sistem pembuluh darah. Protein dan Peradangan Langkah pertama yang dibutuhkan tubuh Anda ketika penyembuhan luka adalah pada fase peradangan. Selama tahap ini, aliran darah ke luka meningkat agar dapat memberikan sel darah putih dan protein ke area luka. Bagian pertama dari tahap ini melibatkan pembersihan situs. Neutrofil, sejenis sel darah putih, bekerja pertama untuk menghilangkan kotoran dan bakteri dari luka. Selanjutnya Monosit jenis lain dari sel darah putih mengikat chemoattractant monosit protein 1, yang merangsang monosit untuk melepaskan granulated fibers untuk menghentikan pendarahan. Pada akhirnya, semua langkah dalam pembentukan pembekuan darah berasal dari kandungan protein. Protein dan Pembentukan Jaringan Tahap kedua untuk penyembuhan luka adalah pertumbuhan kembali kulit, atau pertumbuhan sel-sel epitel pada daerah yang terkena luka. Proses ini dapat terjadi hanya setelah beberapa jam setelah luka. Interaksi antar sel-sel epitel dan extra-cellular protein memungkinkan sel untuk memecah gumpalan darah dan membentuk kulit kembali. Protein dan Remodelling Setelah luka terkendali, tubuh Anda bekerja membangun kembali epidermis dan merekonstruksi pembuluh darah yang rusak. Protein akan bekerja di kedua tahap ini. Protein Fibrin sekarang bertindak sebagai sarana untuk mendukung sel epitel yang baru dibangun. Setelah jaringan epitel dibangun kembali, tubuh bekerja pada restrukturisasi pembuluh darah yang rusak. Protein berkontribusi dengan merangsang pertumbuhan pembuluh baru dan membantu membangun dinding pembuluh darah.

Menurut Cleveland Clinic, orang yang mencoba untuk menyembuhkan luka dapat meningkatkan asupan protein, terutama bagi mereka yang telah menjalani operasi dan luka besar. Mereka menyarankan untuk mengkonsumsi 0,8 1,0 g per kg berat badan Anda. Pilih sumber protein yang sehat seperti ikan, telur, daging dan kacang kedelai.

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http://sehatplus.com/manfaat-protein-untuk-menyembuhkan-luka-operasi.html

Caraalamimengobatidanmenyembuhkanlukabekas operasicaesar
Informasi dan tips cara mengatasi dan mengobati sekaligus menyembuhkan luka bekas operasi caesar atau luka bekas operasi melahirkan caesar dengan obat alami bekas operasi caesar jelly gamat, selain dikonsumsi atau diminum juga dapat doleskan sebagai salep untuk luka bekasoperasicaesaratauoperasimelahirkancaesar. Cara alami mengobati dan menyembuhkan luka bekas operasi melahirkan caesar dengan obat alami jelly gamat merupakan

solusi terbaik yang aman dan alami untuk mempercepat proses penyembuhan dan mempercepat proses pengeringan luka bekas operasi melahirkan caesar. Solusi yang tepat untuk mengatasi dan mengobati sekaligus menyembuhkanluka bekas operasi caesar dengan obat alami jelly gamat gold g atauteripangalias gamat KeringLukaCaesarKarenaTeripang: Sumber : trubusonline: Senin,Juni 16, 200822:27:18 Perasaan berseberangan itu menghinggapi benak Suci Nurhayati. Ia bahagia ketika dokter menyatakan dirinya hamil anak ke3. Namun, ia juga waswas bila melahirkan jabangbayi dengan operasi caesar seperti pada kelahiran anak sebelumnya. Ia ingat persis ketika melahirkan Alexander Wijaya Kusuma, anak keduanya pada 22 Desember 2001. Kepala sang jabangbayi terlilit tali pusar sehingga berakibat nyaris mati lemas. Pascaoperasi ia berharap dapat menjalani hari-hari seperti biasa sebagai karyawan di perusahaan otomotif dari Jerman. Namun, bekas operasi caesar yang membelah perutnya menyisakan nyeri berkepanjangan akibat bengkak dan lama mengering. Perubahan itu disertai siklus menstruasinya tak teratur. Berjalan di pusat perbelanjaan untuk membeli kebutuhan sehari-hari akan dirasakan sebagai sebuah siksaan. Sebab, kerap kali ia merasa lemas dan kakinya bengkak. Selain itu daya tahan tubuhnya lemah. Ia kerap mengalami flu, demam, dan mudah lelah. Ketika gangguan kesehatan itu belum pulih, dokter menyatakan ia hamil pada Maret 2005. Duaoperasi Kecemasannya terbukti. Dokter menyarankan agar ia menjalani operasi caesar untuk melahirkan anak ketiganya. Alasan dokter lantaran usia Suci cukup rawan untuk melahirkan secara normal. Perempuan kelahiran Kuningan, Jawa Barat,

17 Juli 1968 itu menuruti saran dokter. Saat pemeriksaan itu dokter menyatakan cara menutup bekas potongan kulit perut pada operasi caesar sebelumnya tidak rapi. Dampaknya luka lama mengering dan bengkak. Selain itu lemak dan varises menutupi rahim sehingga siklus menstruasinya terganggu. Oleh karena itu dokter yang membantu persalinan menawarkan 2 operasi sekaligus: operasi caesar ke-2 dan operasi membersihkan bekas operasi sebelumnya. Ia mengkombinasikan obat asal Tiongkok untuk mempercepat kesembuhan sekaligus obat yang diresepkan dokter. Namun, hingga 7 bulan luka bekas operasi itu tak kunjung pulih. Iakerap merasa nyeri. Daya tahan tubuh juga acap anjlok, terbukti dengan tingginya frekuensi Suci menderita demam, flu, dan gampang lelah. Dalam kondisi luka belum pulih, ia hamil anak ke-4 pada Desember 2006. Pada kehamilan ke-4 itulah ia rutin mengkonsumsi 2 sendok makan ekstrak teripang setiap hari. Usianya 39 tahun ketika Suci menjalani operasi caesar yang ke-3. Ia menjalaninya dengan percaya diri. Konsumsi ekstrak teripang terus dilanjutkan setelah ia menjalani operasi. Hasilnya sungguh mengagumkan. Hanya sepekan pascaoperasi, luka bekas operasi mengering dan hampir tak berbekas. Ia juga merasa lebih fit dan daya tahan tubuhnya meningkat sehingga tetap bugar meski pekerjaan bertumpuk dan mengurusi keempat anaknya yang membutuhkan tenaga ekstra. Ekstrak teripang membantu menyembuhkan luka operasi? Menurut dr Zen Djaja MD, dokter di Malang, Jawa Timur, ekstrak namakonama teripangdi Jepangbaik diberikan kepada perempuanhamil. Itu lantaran senyawaaktif dan kandungangizi teripangamat lengkap. Prof Zaiton Hassan, peneliti Departemen Ilmu Pangan Universitas Putra Malaysia mengatakan teripang mengandung asam miristat, palmitat, almitoleat, stearat, oleat, linoleat, arakhsidat,eicosapentaenat,behenat,erusat, dan docosahexaenat. Asam lemak itulah yang berperan terhadap pemulihan luka operasi. Kandungan asam eicosapentaenat (EPA) dan asam docosahexaenat (DHA) relatif tinggi, masing-masing 25,69% dan 3,69%. Tingginya kadar EPA menandakan kecepatan teripang memperbaiki jaringan rusak. Kandungan kolagen dalam ekstrak teripang mempercepat penyembuhan luka dalam dan luar setelah pembedahan seperti akibat operasi caesar yang dijalani Suci. Karena teripang cepat memulihkan daya tahan tubuh, makanya para nelayan di negeri jiran mengkonsumsinya sebelum melaut. Di lautanyang berombak ganas, daya tahan tubuh mereka tetap terjaga. Kondisi serupa dialami Suci yang 3 kali menjalani operasi caesar. Lukanya mengering hanya dalam sepekan. Padahal, luka 2 operasi caesar sebelumnya yang ia jalani baru sembuh setelah 7 bulan. (Faiz Yajri).

http://obatpenyakit.net/cara-alami-mengobati/menyembuhkan-luka-bekasoperasi-caesar ---------------Pencegahan Infeksi Luka Operasi

JudulPencegahan Infeksi Luka Operasi PenulisDr. Nucki N Hidajat, SpOT(K), M.Kes, FICS PenerbitUnpad BahasaIndonesia Hak CiptaUnpad Kata Kunciinfeksi, luka operasi Ilmu mengenai infeksi berkembang diawali oleh Hipocrates pada tahun 460 SM. Galen (130-210), Joseph Lister (18271912) mengemukakan teori mengenai infeksi yang selain oleh udara buruk, juga disebabkan oleh adanya kontaminan pada luka terbuka. Lister kemudian mengembangkan zat antiseptic. Ignaz Semmenweis (1818-1865), pada tahun 1847 menemukan bahwa infeksi puerpuralis dapat berkurang secara dramatis jika para pekerja kesehatan melakukan pencucian tangan sebelum tindakan membantu persalinan. Louis Pasteur (1822-1895) menemukan pasteurisasi. Dan Helsted & Caroline Hampton (1852-1922), merupakan bapak Ilmu Bedah Indonesia. Di antara ilmu yang dikembangkannya adalah mengenai sterilisasi, penyembuhan luka dan penutupan luka. Infeksi Luka Operasi ( ILO ) atau Infeksi Tempat Pembedahan (ITP)/Surgical Site Infection (SSI) adalah infeksi pada luka operasi atau organ/ruang yang terjadi dalam 30 hari paska operasi atau dalam kurun 1 tahun apabila terdapat implant. Sumber bakteri pada ILO dapat berasal dari pasien, dokter dan tim, lingkungan, dan termasuk juga instrumentasi. Klasifikasi SSI menurut The National Nosocomial Surveillence Infection (NNIS) terbagi menjadi dua jenis yaitu insisional dibagi menjadi superficial incision SSI yang melibatkan kulit dan subkutan dan yang melibatkan jaringan yang lebih dalam yaitu, deep incisional SSI.

Download: pdf

Pustaka Terkait
Tindakan Kewaspadaan Universal Sebagai Upaya Untuk Mengurangi Resiko Penyebaran Infeksi Surveilans Infeksi Nosokomial Jaminan Pemeliharaan Kesehatan (Jpk) Sebagai Sistem Pendanaan Kesehatan Masyarakat Di Masa Depan

http://pustaka.unpad.ac.id/archives/10798/ -----------------------------------

Wound Healing and Repair

Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Joseph A Molnar, MD, PhD, FACS

Overview
Wound healing is a complex and dynamic process of restoring cellular structures and tissue layers. The human adult wound healing process can be divided into 3 distinct phases: the inflammatory phase, the proliferative phase, and the remodeling phase. Within these 3 broad phases is a complex and coordinated series of events that includes chemotaxis, phagocytosis, neocollagenesis, collagen degradation, and collagen remodeling. In addition, angiogenesis, epithelization, and the production of new glycosaminoglycans (GAGs) and proteoglycans are vital to the wound healing milieu. The culmination of these biological processes results in the replacement of normal skin structures with fibroblastic mediated scar tissue. For more information on wound healing, visit Medscapes Wound Management Resource Center. Image of a long-standing hypotrophic scar is seen below.

A long-standing hypotrophic scar. Patient had abdominal surgery as a child.

This process can go awry and produce an exuberance of fibroblastic proliferation with a resultant hypertrophic scar, which by definition is confined to the wound site. Further exuberance can result in keloid formation (see image below), where scar production extends beyond the area of the original insult. Conversely, insufficient healing can result in atrophic scar formation.

A patient referred for keloid formation after excision of facial cancer and reconstruction

http://emedicine.medscape.com/article/884457-overview

Skin Wound Healing

Overview
Healing...is not a science but the intuitive art of wooing nature. W.H. Auden, "The Art of Healing" Wound healing is a natural restorative response to tissue injury. Healing is the interaction of a complex cascade of cellular events that generates resurfacing, reconstitution, and restoration of the tensile strength of injured skin. Healing is a systematic process, traditionally explained in terms of 3 classic phases: inflammation, proliferation, and maturation. A clot forms and inflammatory cells debride injured tissue during the inflammatory phase. Epithelialization, fibroplasia, and angiogenesis occur during the proliferative phase. Meanwhile, granulation tissue forms and the wound begins to contract. Finally, during the maturation phase, collagen forms tight cross-links to other collagen and with protein molecules, increasing the tensile strength of the scar. For the sake of discussion and understanding, the process of wound healing may be considered a series of separate events. In actuality, the entire process is much more complicated, as cellular events that lead to scar formation occur in tandem. Many aspects of wound healing have yet to be elucidated. Surgeons should have an understanding of the process of wound healing to help produce scars that are cosmetically pleasing and do not impair function. An image depicting a hypertrophic scar can be seen below.

Hypertrophic scarring and keloids. Hypertrophic scars on neck with raised features within scar margins.

For further reading, please see Medscapes Wound Management Resource Center.

Inflammatory Phase
The early events of wound healing are characterized by the inflammatory phase, a vascular and cellular response to injury. An incision made through a full thickness of skin causes a disruption of the microvasculature and immediate hemorrhage. Following incision of the skin, a 5- to 10-minute period of vasoconstriction ensues, mediated by epinephrine, norepinephrine, prostaglandins, serotonin, and thromboxane. Vasoconstriction causes temporary blanching of the wound and functions to reduce hemorrhage immediately following tissue injury, aid in platelet aggregation, and keep healing factors within the wound. Endothelial cells retract to expose the subendothelial collagen surfaces; platelets attach to these surfaces. Adhesion to exposed collagen surfaces and to other platelets occurs through adhesive glycoproteins: fibrinogen, fibronectin, thrombospondin, and von Willebrand factor. The aggregation of platelets results in the formation of the primary platelet plug. Aggregation and attachment to exposed collagen surfaces activates the platelets. Activation enables platelets to degranulate and release chemotactic and growth factors, such as platelet-derived growth factor (PDGF), proteases, and vasoactive agents (eg, serotonin, histamine). The coagulation cascade occurs via 2 different pathways. The intrinsic pathway begins with the activation of factor XII (Hageman factor) when blood is exposed to extravascular surfaces. The extrinsic coagulation pathway occurs through the activation of tissue factor found in extravascular cells in the presence of factors VII and VIIa. Both pathways proceed to the activation of thrombin, which converts fibrinogen to fibrin. The fibrin product is essential to wound healing and is the primary component of the wound matrix into which inflammatory cells, platelets, and plasma proteins migrate. Removal of the fibrin matrix impedes wound healing. In addition to activation of fibrin, thrombin facilitates migration of inflammatory cells to the site of injury by increasing vascular permeability. By this mechanism, factors and cells necessary for healing flow from the intravascular space and into the extravascular space. The result of platelet aggregation and the coagulation cascade is clot formation. Clot formation is limited in duration and to the site of injury. Clot formation dissipates as its stimuli dissipate. Plasminogen is converted to plasmin, a potent enzyme that aids in cell lysis. Clot formation is limited to the site of injury because uninjured nearby endothelial cells produce prostacyclin, an inhibitor of platelet aggregation. In uninjured adjacent areas, antithrombin III binds thrombin, and protein C binds factors of the coagulation cascade, namely, factors V and VII. The vasoconstriction period is followed by a more persistent period of vasodilation mediated by histamine, prostaglandins, kinins, and leukotrienes. Vasodilation is responsible for the erythema, edema, and heat observed after tissue injury. Vasodilation is an important means by which the wound can be exposed to increased blood flow, accompanied by the necessary inflammatory cells and factors that fight infection and debride the wound of devitalized tissue. Alterations in pH (secondary to tissue and bacterial degradation), swelling, and tissue hypoxemia at the injury site contribute to the sensation of wound pain.

Following injury, the products of the earliest cellular events activate intricately related inflammatory pathways that modify subsequent events in the wound-healing process. For example, Hageman factor activates the kinin pathway, which produces bradykinin. Bradykinin stimulates vasodilation and increased vascular permeability. Histamine released from platelets and circulating mast cells increases vascular permeability and indirectly stimulates vasodilation through the production of prostaglandins E1 and E2. Prostaglandins cause vasodilation through the activation of the adenylate cyclase pathway via the production of cyclic adenosine monophosphate. Prostaglandins also accumulate at the area of injury through the activation of phospholipases located on injured cell membranes. Phospholipases stimulate the release of arachidonic acid, ultimately leading to the production of prostaglandins, leukotrienes, and other factors. Hageman factor also activates the classic complement pathway during the inflammatory phase. Inactive proteins of the complement system (ie, C1-C9) are activated by means of a cascade of reactions. These proteins stimulate important inflammatory events such as chemotaxis, degranulation of mast cells, and cytolysis. C5a and C567 are chemotactic agents for neutrophil migration. C3a, C4a, and C5a cause degranulation of mast cells, leading to release of histamine and increased vascular permeability. The membrane attack complex, C5b6789, is responsible for cytolysis. The cellular aspect of the inflammatory phase occurs within hours of injury. Neutrophils are the predominant cell type for the first 48 hours after injury but do not appear essential to the wound-healing process. Neutrophils cleanse the wound site of bacteria and necrotic matter and release inflammatory mediators and bactericidal oxygen-free radicals. The absence of neutrophils does not prevent healing. Macrophages are essential to wound healing and perhaps are the most important cells in the early phase of wound healing. Macrophages phagocytose debris and bacteria. Macrophages also secrete collagenases and elastases, which break down injured tissue and release cytokines. In addition, macrophages release PDGF, an important cytokine that stimulates the chemotaxis and proliferation of fibroblasts and smooth muscle cells. Finally, macrophages secrete substances that attract endothelial cells to the wound and stimulate their proliferation to promote angiogenesis. Macrophage-derived growth factors play a pivotal role in new tissue formation, as evidenced by the fact that new tissue formation in macrophage-depleted animal wounds demonstrates defective repair. In studies in which experimental wounds are rendered monocytopenic, subsequent stages of fibroplasia and granulation tissue formation are impaired and the overall rate of wound healing is delayed. T lymphocytes migrate into the wound during the inflammatory phase, approximately 72 hours following injury. T lymphocytes are attracted to the wound by the cellular release of interleukin 1, which also contributes to the regulation of collagenase. Lymphocytes secrete lymphokines such as heparin-binding epidermal growth factor and basic fibroblast growth factor. Lymphocytes also play a role in cellular immunity and antibody production.

Proliferative Phase
Formation of granulation tissue is a central event during the proliferative phase. Inflammatory cells, fibroblasts, and neovasculature in a matrix of fibronectin, collagen, glycosaminoglycans, and proteoglycans comprise the granulation tissue. Granulation tissue formation occurs 3-5 days following injury and overlaps with the preceding inflammatory phase.

Epithelialization
Epithelialization is the formation of epithelium over a denuded surface. Epithelialization of an incisional wound involves the migration of cells at the wound edges over a distance of less than 1 mm, from one side of the incision to the other. Incisional wounds are epithelialized within 24-48 hours after injury. This epithelial layer provides a seal between the underlying wound and the environment. The process begins within hours of tissue injury. Epidermal cells at the wound edges undergo structural changes, allowing them to detach from their connections to other epidermal cells and to their basement membrane. Intracellular actin microfilaments are formed, allowing the epidermal cells to creep across the wound surface. As the cells migrate, they dissect the wound and separate the overlying eschar from the underlying viable tissue. In superficial wounds (eg, wounds due to laser resurfacing, dermabrasion, chemical peel treatments) adnexal structures (eg, sebaceous glands, hair follicles) contribute to reepithelialization. Epidermal cells secrete collagenases that break down collagen and plasminogen activator, which stimulates the production of plasmin. Plasmin promotes clot dissolution along the path of epithelial cell migration. The extracellular wound matrix over which epithelial cells migrate has received increased emphasis in wound-healing research. Migrating epithelial cells interact with a provisional matrix of fibrin cross-linked to fibronectin and collagen. The matrix components may be a source of cell signals to facilitate epithelial cell proliferation and migration. In particular, fibronectin seems to promote keratinocyte adhesion to guide these cells across the wound base. Wounds in a moist environment demonstrate a faster and more direct course of epithelialization. Occlusive and semiocclusive dressings applied in the first 48 hours after injury may maintain tissue humidity and optimize epithelialization. When epithelialization is complete, the epidermal cell assumes its original form, and new desmosomal linkages to other epidermal cells and hemidesmosomal linkages to the basement membrane are restored.

Fibroplasia
The fibroblast is a critical component of granulation tissue. Fibroblasts are responsible for the production of collagen, elastin, fibronectin, glycosaminoglycans, and proteases Fibroblasts grow in the wound as the number of inflammation cells decrease. The demand for inflammation disappears as the chemotactic factors that call inflammatory cells to the wound are no longer produced and as those already present in the wound are inactivated. Fibroplasia begins 3-5 days after injury and may last as long as 14 days. Skin fibroblasts and mesenchymal cells differentiate to perform migratory and contractile capabilities. Fibroblasts migrate and proliferate in response to fibronectin, platelet-derived

growth factor (PDGF), fibroblast growth factor, transforming growth factor, and C5a. Fibronectin serves as an anchor for the myofibroblast as it migrates within the wound. The synthesis and deposition of collagen is a critical event in the proliferative phase and to wound healing in general. Collagen consists of 3 polypeptide chains, each twisted into a left-handed helix. Three chains of collagen aggregate by covalent bonds and twist into a right-handed superhelix, forming the basic collagen unit. A striking structural feature of collagen is that every third amino acid is glycine. This repeating structural feature is an absolute requirement for triple-helix formation. Collagen is rich in hydroxylysine and hydroxyproline moieties, which enable it to form strong cross-links. The hydroxylation of proline and lysine residues depends on the presence of oxygen, vitamin C, ferrous iron, and -ketoglutarate. Deficiencies of oxygen and vitamin C, in particular, result in underhydroxylated collagen that is less capable of forming strong cross-links and, therefore, is more vulnerable to breakdown. Collagen is secreted to the extracellular space in the form of procollagen. This form is then cleaved of its terminal segments and called tropocollagen. Tropocollagen can aggregate with other tropocollagen molecules to form collagen filaments. Filaments consist of tropocollagen molecules arrayed in a staggered fashion, joined by intermolecular cross-links. Filaments aggregate to form fibrils. Collagen fibrils, in turn, aggregate to form collagen fibers. Filament, fibril, and fiber formation occur within a matrix gel of glycosaminoglycans, hyaluronic acid, chondroitin sulfate, dermatan sulfate, and heparin sulfate produced by fibroblasts. Intermolecular cross-links within the collagen fiber stabilize it, making it resistant to destruction. Age, tension, pressure, and stress affect the rate of collagen synthesis. Collagen synthesis begins approximately 3 days after injury and may continue at a rapid rate for approximately 2-4 weeks. Collagen synthesis is controlled by the presence of collagenases and other factors that destroy collagen as new collagen is made. Approximately 80% of the collagen in normal skin is type I collagen; the remaining is mostly type III. In contrast, type III collagen is the primary component of early granulation tissue and is abundant in embryonic tissue. Collagen fibers are deposited in a framework of fibronectin. An essential interaction seems to exist between fibronectin and collagen; experimental wounds depleted of fibronectin demonstrate decreased collagen accumulation. Elastin is also present in the wound in smaller amounts. Elastin is a structural protein with random coils that allow for stretch and recoil properties of the skin.

Angiogenesis
A rich blood supply is vital to sustain newly formed tissue and is appreciated in the erythema of a newly formed scar. These blood vessels disappear as they become unnecessary, as does the erythema of the scar. The macrophage is essential to the stimulation of angiogenesis and produces macrophage-derived angiogenic factor in response to low tissue oxygenation. This factor functions as a chemoattractant for endothelial cells. Basic fibroblast growth factor secreted by the macrophage and vascular endothelial growth factor secreted by the epidermal cell are also important to angiogenesis. Fibronectin is chemotactic for endothelial cells. Capillaries bud from existing capillaries in response to these growth factors. Endothelial cells coalesce and bind fibrin, which adds support to the vessel wall. Angiogenesis results in greater blood flow to the wound and, consequently, increased perfusion of healing factors. Angiogenesis ceases as the demand for new blood vessels ceases. New blood vessels that become unnecessary disappear by apoptosis. New blood vessel formation is a complex process that relies on several angiogenic factors such as vascular endothelial growth factor, angiogenin, and angiotropin.

Contraction
Wound contraction begins almost concurrently with collagen synthesis. Contraction, defined as the centripetal movement of wound edges that facilitates closure of a wound defect, is maximal 5-15 days after injury. Contraction results in a decrease in wound size, appreciated from end to end along an incision; a 2-cm incision may measure 1.8 cm after contraction. The maximal rate of contraction is 0.75 mm/d and depends on the degree of tissue laxity and shape of the wound. Loose tissues contract more than tissues with poor laxity, and square wounds tend to contract more than circular wounds. Wound contraction depends on the myofibroblast located at the periphery of the wound, its connection to components of the extracellular matrix, and myofibroblast proliferation. Radiation and drugs, which inhibit cell division, have been noted to delay wound contraction. Contraction does not seem to depend on collagen synthesis. Although the role of the peripheral nervous system in wound healing is not well delineated, recent studies have suggested that sympathetic innervation may affect wound contraction and epithelialization through unknown mechanisms. Contraction must be distinguished from contracture, a pathologic process of excessive contraction that limits motion of the underlying tissues and is typically caused by the application of excessive stress to the wound.

MATURATION PHASE

Collagen
Collagen remodeling during the maturation phase depends on continued collagen synthesis in the presence of collagen destruction. Collagenases and matrix metalloproteinases in the wound assist removal of excess collagen while synthesis of new collagen persists. Tissue inhibitors of metalloproteinases limit these collagenolytic enzymes, so that a balance exists between formation of new collagen and removal of old collagen.

During remodeling, collagen becomes increasingly organized. Fibronectin gradually disappears, and hyaluronic acid and glycosaminoglycans are replaced by proteoglycans. Type III collagen is replaced by type I collagen. Water is resorbed from the scar. These events allow collagen fibers to lie closer together, facilitating collagen cross-linking and ultimately decreasing scar thickness. Intramolecular and intermolecular collagen cross-links result in increased wound bursting strength. Remodeling begins approximately 21 days after injury, when the net collagen content of the wound is stable. Remodeling may continue indefinitely. The tensile strength of a wound is a measurement of its load capacity per unit area. The bursting strength of a wound is the force required to break a wound regardless of its dimension. Bursting strength varies with skin thickness. Peak tensile strength of a wound occurs approximately 60 days after injury. A healed wound only reaches approximately 80% of the tensile strength of unwounded skin.

Cytokines
Cytokines have emerged as important mediators of wound healing events. By definition, a cytokine is a protein mediator, released from various cell sources, which binds to cell surface receptors to stimulate a cell response. Cytokines can reach their target cell by endocrine, paracrine, autocrine, or intracrine routes. Some important cytokines are described as follows:

Epidermal growth factor was the first cytokine described and is a potent mitogen for epithelial cells, endothelial cells, and fibroblasts. Epidermal growth factor stimulates fibronectin synthesis, angiogenesis, fibroplasia, and collagenase activity. Fibroblast growth factor is a mitogen for mesenchymal cells and an important stimulus for angiogenesis. Fibroblast growth factor is a mitogen for endothelial cells, fibroblasts, keratinocytes, and myoblasts. This factor also stimulates wound contraction and epithelialization and production of collagen, fibronectin, and proteoglycans. PDGF is released from the alpha granules of platelets and is responsible for the stimulation of neutrophils and macrophages and for the production of transforming growth factor-. PDGF is a mitogen and chemotactic agent for fibroblasts and smooth muscle cells and stimulates angiogenesis, collagen synthesis, and collagenase. Vascular endothelial growth factor is similar to PDGF but does not bind the same receptors. Vascular endothelial growth factor is mitogenic for endothelial cells and plays an important role in angiogenesis. Transforming growth factor- is released from the alpha granules of platelets and has been shown to regulate its own production in an autocrine manner. This factor is an important stimulant for fibroblast proliferation and the production of proteoglycans, collagen, and fibrin. The factor also promotes accumulation of the extracellular matrix and fibrosis. Transforming growth factor- has been demonstrated to reduce scarring and to reverse the inhibition of wound healing by glucocorticoids. Tumor necrosis factor- is produced by macrophages and stimulates angiogenesis and the synthesis of collagen and collagenase. Tumor necrosis factor- is a mitogen for fibroblasts.

Abnormal Wound Healing: Keloids and Hypertrophic Scars Keloids and hypertrophic scars are characterized by an accumulation of excess collagen and are distinguished from each other by their appearance. Keloids grow beyond the borders of the original wound and do not tend to resolve spontaneously. Hypertrophic scars stay within the limit of the original wound and do tend to regress spontaneously. Hypertrophic scars are generally seen soon after tissue injury, whereas keloids can form as late as a year after injury. Hypertrophic scars tend to be associated with a contracture across a joint surface. Upon histological examination, keloids and hypertrophic scars differ from normal skin by a rich blood supply, high mesenchymal density, and a thick epidermal layer. The collagen fibers in hypertrophic scars are loosely arrayed in a wavy pattern. Keloids demonstrate a disorganized pattern of large, irregularly shaped collagen fibers with a lower content of collagen cross-links compared to normal skin. Keloids also contain a greater amount of type III collagen than a mature scar, which suggests a failure in scar maturation. Little is known about the etiology of keloid and hypertrophic scar formation. Abnormalities in cell migration, proliferation, inflammation, and the synthesis and secretion of extracellular matrix proteins, cytokines, and remodeling have all been associated with keloid and hypertrophic scar formation. Increased activity of fibrogenic cytokines and exaggerated responses to cytokines have been described. Transforming growth factor- (TGF-) appears to play an integral role in aberrant healing. More recently, abnormal interactions between epidermal-mesenchymal cells and regulatory genes, such as TP53, have been proposed. That certain patients and conditions may predispose to hypertrophic scar formation is well known. Both hypertrophic scars and keloids occur more commonly in dark-skinned individuals. Wounds that cross skin tension lines or wounds that are located on the ear lobes or presternal and deltoid areas are common sites for these forms of abnormal healing. The role of wound tension has been examined and found to be related to the exaggerated response to tension of keloid fibroblasts relative to normal fibroblasts with regard to production of pro-fibrotic growth factors. A single, optimal treatment technique for hypertrophic scars and keloids has not been developed, and the recurrence rate of these abnormal scars is high. Surgical management is reserved for cases that are unresponsive to conservative management. Conservative management includes pharmacologic therapy, pressure, laser, and radiotherapy. Each method has varying degrees of reported success. Recent work has demonstrated that treatment of fibroblasts with the combined CO2 and Er:YAG lasers alters the differential expression of mediators responsible for fibrosis and collagen formation and organization. Laser therapy may play a role in the prevention of keloid and hypertrophic scar formation.

-Fetal Wound Healing Studies and the Future The study of fetal wound healing is intriguing and may result in the discovery of an optimal method that would allow wounds to heal without scar formation. Wounds occurring in fetuses of early gestational age can heal without any scar formation. The difference in the wound environment in fetal wounds occurring in early gestation has been speculated to account for the absence of scar formation. Proposed contributing factors to scarless healing in fetal wounds are the presence of fewer neutrophils and more monocytes during the inflammatory period, different concentrations of cytokines, and a greater proportion of type III collagen in contrast to adult wounds. Transforming growth factor-b (TGF-bspecifically, low levels of TGF-b1 and TGF-b2 and high levels of TGF-b3probably has a central role in scar formation, and studies of its role are ongoing. Low levels of platelet-derived growth factor (PDGF), a greater amount of epidermal growth factor (a mitogen for epithelialization), a faster rate of wound healing, and a greater amount of hyaluronic acid in the extracellular matrix has been documented and suggests a more efficient process of wound healing in fetal models. Notably, collagen deposition in fetal wounds displays a fine reticular pattern that is indistinguishable from uninjured skin. In addition, fibronectin is more abundant in fetal wounds and has been noted to accelerate wound healing in fetal rat models. In neonates, fibroblasts have a potent collagen-producing response to TGF-b. In fetal skin, this response is blunted and short lived. There is less differentiation of fibroblasts into myofibroblasts, and this differentiation is briefer. Downstream mediators of the TGF-b pathway such as Smad2/3 and c-Jun N-terminal kinase were decreased compared with neonate skin. [1] Although evidence indicates that early fetal wound models heal more efficiently than adult wounds, the explanation of this more-efficient process is under investigation. The explanation may also lie in alterations of the wound environment to mimic fetal wound models. Evidence shows that the healing environment may be manipulated in other ways to enhance or to accelerate the healing process. Recent animal studies demonstrate beneficial effects of both laser and electrical stimulation of tissues during the inflammatory, proliferative, and maturation phases of wound healing. Based on the assumption that proteins found in the blood can promote healing, the application of platelet-rich plasma has been investigated and found to foster increased levels of inflammatory cells during the healing process without affecting final cell counts in healed tissue. In healthy individuals, platelet-rich plasma may accelerate wound closure in full-thickness dermal wounds. However, it does not alter the long-term architecture of a healed wound.[2] Platelet-derived growth factor D alone may increase the rate of macrophage recruitment and angiogenesis, but its overall long-term effect is not established.[3] Pulsed magnetic field therapy is also being investigated as a means to help wound healing. In rats, it has been shown to accelerate cutaneous wound healing.[4] The used of these novel modalities and techniques in the clinical setting remains to be determined.

http://emedicine.medscape.com/article/884594-overview#aw2aab6b6 -------

Wound Healing and Growth Factors

Author: Allen Gabriel, MD; Chief Editor: Joseph A Molnar, MD, PhD, FACS

Overview
Tremendous advancements have been made in understanding the processes of wound healing. The cell types and the order in which they appear in the wound have been established; many growth factors and their functions have been elucidated. [1] Despite the advances in understanding the science of wound healing, many more steps have yet to be discovered and elucidated. The frontier of this field includes the prevention of hypertrophic and keloid scar formation and, ultimately, any visual remnant of the wound. An incision created by a scalpel, trauma resulting from a bullet, or tissue death caused by a myocardial infarction all undergo a similar and predictable reparative process. Understanding how the body repairs damaged tissue and what factors influence the wound healing process helps the surgeon ensure an acceptable outcome from surgery. Tissue injury is common thread to every medical specialty. Wound healing in any tissue follows a predictable sequence of events. A broad understanding of the sequence of events, cells involved, relative time table, and molecular signaling can allow for maximum optimization of this important patient care issue. Although seemingly basic in concept, advances in molecular science have allowed modern medicine to gain a true appreciation of the complex interplay between the cells involved in the phases of wound healing. As greater understanding of the growth factors involved in wound healing emerges, future patient care may include scarless wound healing and transplant of tissues engineered from stem cell progenitors.

Types of Wound Healing

The 3 categories of wound closure are primary, secondary, and tertiary. Primary healing involves closure of a wound within hours of its creation. Secondary healing involves no formal wound closure; the wound closes spontaneously by contraction and reepithelialization. Tertiary wound closure, also known as delayed primary closure, involves initial debridement of the wound for an extended period and then formal closure with suturing or by another mechanism.

Phases of Wound Healing

Knowledge of the phases of wound healing allows the practitioner to counsel patients effectively and treat wounds appropriately. The typical wound, after primary closure, may take over a year to fully mature; the appearance of the scar may dramatically change during this time. Thus, all wounds should be at least 1 year old before scar revision is considered. The wound healing process has 3 phases. They are the inflammatory phase, the proliferative phase, and the remodeling phase.[2] The inflammatory phase is characterized by hemostasis and inflammation. Collagen exposed during wound formation activates the clotting cascade (both the intrinsic and extrinsic pathways), initiating the inflammatory phase. After injury to tissue occurs, the cell membranes, damaged from the wound formation, release thromboxane A2 and prostaglandin 2-alpha, potent vasoconstrictors. This initial response helps to limit hemorrhage. After a short period, capillary vasodilatation occurs secondary to local histamine release, and the cells of inflammation are able to migrate to the wound bed. The timeline for cell migration in a normal wound healing process is predictable.

Wound healing and growth factors. Cells involved in wound healing. The cells appearing in a wound are depicted in sequence from left to right, and the color bars represent the range of days each cell type is in the wound.

Inflammatory phase
The inflammatory phase begins at the time of injury and lasts 2-4 days. The phase begins with hemostasis and formation of the platelet plug. Platelets release platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-b) from their alpha granules to attract neutrophils and macrophages. Neutrophils scavenge for bacteria and foreign debris. Macrophages are the most important mediators of wound healing. Macrophages continue to emit growth factors to attract fibroblasts and usher in the next phase of wound healing (see Table below).

Proliferative phase
The proliferative phase begins on approximately day 3; it overlaps with the inflammatory phase. The most important cell is the fibroblast. Fibroblasts peak approximately day 7 from injury and are responsible for initiating angiogenesis, epithelialization, and collagen formation. Epithelialization is from the basement membrane if the basement membrane remains intact (eg, first-degree burn). If the basement membrane is not intact, the epithelialization is from the wound edges. Fibroblasts produce mainly type III collagen during this phase. Granulation tissue, formed in this phase, is particularly important in wounds healing by secondary intention. When collagen synthesis and breakdown become equal, the next phase of wound healing has begun.

Remodeling phase
Increased collagen production and breakdown continue for 6 months to 1 year after injury. The initial type III collagen is replaced by type I collagen until a type I:type II ratio of 4:1 is reached, which is equal to normal skin. Also, fibroblasts differentiate into myofibroblasts, causing tissue contraction during this phase of wound healing. Collagen reorganizes along lines of tension and crosslinks, giving added strength. Strength eventually approaches 80% of the strength of uninjured tissue. Vascularity decreases, producing a less hyperemic and more cosmetically appealing wound as this phase progresses. The timetable for wound healing can be quite variable. Chronic wounds can stall in the inflammatory phase because of poor perfusion, poor nutrition, or a myriad of other factors causing excessive buildup of exudates in the wound base. These wounds tend to remain unhealed unless active and aggressive means are undertaken to correct the underlying comorbidities while providing proper wound care. Healing may also become exaggerated in keloid and hypertrophic scar formation. Excessive type III collagen formation in the proliferative phase causes an overgrowth of scar tissue in these wounds. The etiology is multidimensional. Individuals with darkly pigmented skin are genetically prone to keloid formation. Certain areas of the body, such as the sternum and shoulder, are more prone to hypertrophic scar formation. Phases can also be blunted as in the fetus, which has a decreased inflammatory phase and heals without scar. Experiments evaluating fetus wound healing have found a higher level of TGF-b3 than in adults.[3] This is thought to antagonize the effects of TGF-b2 and TGF-b1 found to be upregulated in keloids and hypertrophic scars. Thus, a greater understanding of the growth

factors in fetus healing may lead to novel therapy for scarless wound healing and treatment of keloid and hypertrophic scars. Human trials are currently underway.[3] Collagen types and locations are as follows:

Type I - Located in all connective tissue except hyaline cartilage and basement membranes Type II - Located in hyaline cartilage Type III - Located in distensible connective tissue (blood vessels) Type IV - Located in basement membranes Type V - Located in all tissues Type VI - Located in all tissues Type VII - Located in the dermal-epidermal junction Type VIII - Located in the Descemet membrane Type IX - Located in hyaline cartilage Type X - Located in hypertrophic cartilage and hyaline cartilage

Local cytokines
Growth factors represent the intercellular signaling that orchestrates the complex sequence of cell migration, division, differentiation, and protein expression during wound healing. The 8 major families of growth factors are expressed in varying levels by the cells involved with healing. Table. Growth Factors (Open Table in a new window)

Growth Factor
1. Epidermal Growth Factor (EGF)

Production
Platelets, macrophages

Known Effects
Stimulates fibroblasts to secrete collagenase to degrade the matrix during the remodeling phase. Stimulates keratinocyte and fibroblast proliferation. May reduce healing time when applied topically. TGF-a: Mitogenic and chemotactic for keratinocytes and fibroblasts

2. Transforming Growth Factor

Platelets, macrophages, lymphocytes, hepatocytes

TGF-b1 and TGF-b2: Promotes angiogenesis, up-regulates collagen production and inhibits degradation, promotes chemoattraction of inflammatory cells.

TGF-b3 (antagonist to TGF-b1 and b2): Has been found in high levels in fetal scarless wound healing and has promoted scarless healing in adults experimentally when TGF-b1 and TGF-b2 are suppressed.

3. Vascular Endothelial Growth Factor (VEGF) 4. Fibroblast Growth Factor (FGF)

Endothelial cells

Promotes angiogenesis during tissue hypoxia.

Macrophages, mast cells, Tlymphocytes

Promotes angiogenesis, granulation, and epithelialization via endothelial cell, fibroblast, and keratinocyte migration, respectively. Attracts macrophages and fibroblasts to zone of injury. Promotes collagen and proteoglycan synthesis.

5. Platelet-Derived Platelets, macrophages, and Growth Factor endothelial cells (PDGF) 6. Interleukins Macrophages, keratinocytes, endothelial cells, lymphocytes,

IL-1: Proinflammatory, chemotactic for neutrophils, fibroblasts, and keratinocytes. Activates neutrophils

fibroblasts, osteoblasts, basophils, mast cells IL-4: Activates fibroblast differentiation. Induces collagen and proteoglycan synthesis.

IL-8: Chemotactic for neutrophils and fibroblasts.

7. ColonyStimulating Factors

Stromal cells, fibroblasts, endothelial cells, lymphocytes

Granulocyte colony stimulating factor (G-CSF): Stimulates granulocyte proliferation.

Granulocyte Macrophage Colony Stimulating Factor (GMCSF): Stimulates granulocyte and macrophage proliferation.

8. Keratinocyte growth factor

Fibroblasts

Stimulates keratinocyte migration, differentiation, and proliferation.

Wound optimization
Creating conditions that allow for proper wound healing can make all the difference in various wounds, from an inconspicuous wound after plastic surgery to an amputation or even death in a patient with severe vascular disease or burn. When approaching an injured patient, the following list can guide the thought process of the physician or caretaker in optimizing healing conditions.

Perfusion: Tissues cannot heal without the cells, oxygen, and nutrients that the cardiovascular system delivers. [4] This is particularly important in the wound healing of patients with diabetes or paraplegia, patients who smoke, and patients who have been exposed to radiation. Patients with severe vascular disease may experience enhanced wound healing via increased perfusion after a vascular bypass or related procedure. Patients who smoke should cease smoking immediately in the event of major surgery or injury. Nicotine causes severe vasoconstriction, and the toxins in cigarette smoke can greatly decrease the ability of tissues to heal. Paraplegics and diabetics with neuropathy must cease all substance abuse and be continually educated and reinforced on the need for pressure relief to avoid pressure ulcers. In the event of pressure sore discovery, absolute pressure relief to increase perfusion is paramount. Infection: Infection is defined as having quantitative bacterial counts of 105 colony forming units per gram of tissue. Infected wounds do not heal because of decreased epithelialization and increased collagen breakdown. These wounds should be appropriately cleared of infection by drainage, debridement, and the administration of appropriate antibiotics. Nutrition:[5] When assessing nutritional status, certain serum nutritional markers can be helpful. Albumin is a good marker of overall long-term nutritional status over the last month; ideally, it should be at least 3.5 g/dL to optimize wound healing. Prealbumin can offer a more recent nutritional status picture and should be maintained above 17 g/dL. Caloric needs of the severely injured patient can exceed 35 kcal/kg/d and 0.8-2 g/kg/d of protein and should be continually assessed and adjusted according to the stage of healing and injury. This is particularly true for burn patients who require multiple debridements and grafting. Vitamin supplementation has not been proven to increase wound healing unless a specific deficiency exists.[6] Vitamin A is an exception to this rule and is detailed below. Steroids: Corticosteroids can blunt the response of macrophages, the most essential cell in wound healing. [2] Vitamin A, insulinlike growth factor (IGF), and oxandrolone (anabolic steroid) can be given to reverse the effects of corticosteroids on wound healing. Dressing: Numerous dressings are available on the market. Many claim that they need to be changed less often than other dressings. This may be true for a clean wound. However, there is no substitute for frequent dressing changes in a grossly contaminated or recently debrided infected wound. Other basic principles apply. The wound should be kept moist (but not wet) at all times. Desiccated tissue is dead tissue and must be sharply debrided. With the advent of negative pressure wound dressing, wound healing for even chronic wounds can be greatly increased. Again, great prudence should be used; apply negative pressure wound dressing only when indicated. Currently, cytokines have a limited role in clinical practice. The only currently available commercial product proven to be efficacious in randomized, double-blind studies is platelet-derived growth factor (PDGF), available as recombinant human PDGF-BB. In multiple studies, recombinant human PDGF-BB has been demonstrated to reduce healing time and improve the incidence of complete wound healing in stage III and IV ulcers.[7] Many other cytokines currently under study in vitro include transforming growth factor beta (TGF-b), epidermal growth factor (EGF), and IGF-1. Proper wound healing involves a complex interaction of cells and cytokines working in concert. In recent years, more chemical mediators integral to this process have been identified. The sequential steps and specific processes have not been fully

differentiated. When examining the process of wound healing, one should identify the major steps and know the important mediators. Wound Healing Terms Primary closure: A wound closed surgically with sutures or by other means soon after creation is considered a primary closure. Secondary closure: This type of closure is appropriate for infected or contaminated wounds in areas of poor blood supply. The wound fills with granulation tissue, contracts, and reepithelializes. This leads to a worse scar from a prolonged inflammatory phase. Tertiary closure (delayed primary closure): This type of closure allows for a superior cosmetic appearance to the closure of a contaminated wound. The wound is allowed to stay open and undergo repeat dressing changes for a few days. This decreases the bioburden of the wound and allows for a decreased infection rate after surgical closure a few days later. Acute wound: A wound is acute if it occurred in the last 4-6 weeks. Chronic wound: A wound is chronic if it has been present for longer than 4-6 weeks.

http://emedicine.medscape.com/article/1298196-overview#aw2aab6b4

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Factors Affecting Wound Healing (Schwartz)