讀書筆記
當你快速翻閱這本書時，紙張會切入你的一根手指。 人體就像一個管弦樂隊一樣，傷口愈合是一首由四個重疊樂章組成的交響樂：止血、炎症、增殖和成熟。 止血的英文(Hemostasis)=由血液+停止兩部分構成。 這是身體試圖止血。 當紙切開皮膚時，血管破裂會使循環中的血小板暴露於膠原蛋白中，膠原蛋白形成位於血管壁內襯下麵的有彈性的結締組織基質。 這種接觸啟動了血液凝固過程，引發凝血級聯反應，這是血小板和化學信使之間的生化對位，導致凝塊形成並奠定修複細胞可以發揮作用的基質。 承擔起駕駛員的協調職責，血小板釋放的細胞因子推動管弦樂隊進入下一個樂章，該樂章以炎症反應的漸強開始。
在這快速而誇張的第二樂章中，中性粒細胞是最先設定緊迫旋律的白細胞。 這些吞噬細胞協調先天性和適應性免疫反應。 它們被血小板釋放的介質所吸引，從而受到化學傷害。 這些介質還會使該區域的血管更加滲漏，促進更多白細胞的遷移，並順便使傷口周圍的皮膚腫脹。 中性粒細胞會產生更多的炎症細胞因子，例如 IL-1α 和 IL-1β，通過調用其他白細胞通過協調、不協調和最終解決來分層和諧，從而增強炎症反應。 當中性粒細胞開始吞噬細菌時，它們就開始了這種諧波探索。
巨噬細胞和白細胞是下一個加入炎症運動的白細胞，其中巨噬細胞處於領先地位。 它們通過釋放稱為自由基的分子（例如活性氧）來阻止細菌的生長。 這些自由基會對細菌和我們自己的細胞造成損害。 巨噬細胞還釋放一氧化氮，這也會導致局部血管擴張，通過其他免疫細胞為受傷部位帶來更多的血液援助。 那是低音下降的時候。 當一氧化氮合成受到損害（如糖尿病）時，傷口愈合也會受到損害。 在發揮作用的同時，巨噬細胞也會清理舞台，吞噬死亡的細菌和其他碎片，並使用酶去除和消化傷口上的死亡組織。 它們還調節新皮膚在其上生長的腳手架的創建。 同時，他們呼籲並邀請將增殖形成新皮膚的細胞和將刺激新血管生長的細胞的參與。
傷口愈合的第三個動作是增殖。 新的聲音出現，帶來了修複的希望。 成纖維細胞、內皮細胞和上皮細胞在那裏設定情緒。 它們受到血小板和巨噬細胞釋放的細胞因子和生長因子的誘導，沉積出治愈皮膚所需的物質。 而炎症運動則充滿了張力。 成纖維細胞遷移到傷口部位，在那裏產生足夠的膠原蛋白，這表明傷口修複的精確、顯著的生物控製。 構成血管內壁的內皮細胞會產生新血管，這一過程稱為血管生成。 同樣，形成皮膚外層的上皮細胞在傷口邊緣開始增殖，以響應相同的炎症細胞因子和生長因子來覆蓋傷口。
最後的樂章，結局，是成熟。 在這裏，前一個樂章的主題被分解，並闡述了一個更強但更慢的變奏——慢板。 原來的凝塊被溶解，最初沉積的膠原蛋白被另一種膠原蛋白取代，從而增加了傷口的整體拉伸強度。 構成傷口愈合床的肉芽組織被疤痕所取代。 然後，這種運動會持續數月，重塑發生在細胞水平上，細胞與它們產生的細胞外基質和周圍的細胞外基質之間進行著美妙的呼喚和反應。 三個月後，疤痕達到最大抗拉強度，僅為未受傷皮膚的 80%。 免疫細胞安靜下來，傷口修複過程停止，愈合完成。
As you speed through the pages of this book, the paper slices into one of your fingers. Cue the orchestra, Wound healing is a symphony in four overlapped movements: hemostasis, inflammation, proliferation, and maturation. Hemostasis = blood + stoppage. It is the body’s attempt to staunch bleeding. When paper slices skin, the rupture of blood vessels exposes circulating platelets to the protein collagen, which forms the stretchy matrix of connective tissue that sits right under the vessel wall’s inner lining. This contact starts the process of blood clotting, setting off the coagulation cascade, a biochemical counterpoint between platelets and chemical messengers, that leads to clot formation and laying down the matrix upon which repair cells can work. Assuming the coordinating duties of conductor, cytokines released by platelets motion the orchestra to the next movement, which opens with a crescendo in the inflammatory response.
In this second movement, which is fast and bombastic, neutrophils are the first white blood cells to set the urgent melody. These are phagocytes that harmonize the innate and adaptive immune responses. They are chemically drawn to the injury by the mediators that the platelets released. These mediators also make the blood vessels in the area leakier, facilitating the migration of more white blood cells- and incidentally swelling the skin around the cut. Neutrophils make even more inflammatory cytokines, such as IL-1alpha and IL-1beta, amping up the inflammatory response by calling in other white blood cells to layer the harmony, by way of consonance, dissonance, and ultimately resolution. Neutrophils tart this harmonic exploration as they begin eating up bacteria.
Macrophages and leukocytes are the next white blood cells to join the inflammatory movement, with macrophages taking the lead. They stop bacteria in their tracks by releasing molecules called free radicals, such as reactive oxygen species. These free radicals cause damage to the bacteria and to our own cells. Macrophages also release nitric oxide, which also causes local blood vessels to dilate, bringing more blood-borne assistance by way of other immune cells to the site of injury. That’s when the bass drops. When nitric oxide synthesis is impaired as it is in diabetes, wound healing is also impaired. As they play their part, macrophages also clean up the stage, phagocytizing dead bacteria and other debris and using enzymes to remove and digest dead tissue from the wound. They also regulate the creation of the scaffolding upon which the new skin will grow. At the same time, they call on and invite the participation of cells that will proliferate to make the new skin and cells that will stimulate the growth of new blood vessels.
The third movement of wound healing is proliferation. New voices emerge, bringing the promise of repair. Fibroblasts, endothelial cells, and epithelial cells set the mood there. They are coaxed by the cytokines and growth factors released by platelets and macrophages to lay down the substances needed to heal the skin. While the inflammatory movement was full of tension. Fibroblast migrate to the wound site, where they produce collagen just until enough has been laid down - indicating the precise, remarkable biological control of wound repair. Endothelial cells, which constitute the inner lining of blood vessels, create new blood vessels - a process called angiogenesis. Likewise, epithelial cells, which form the skin’s outer layer, start proliferating at the wound’s edges to cover it up in response to the same inflammatory cytokines and growth factors.
The final movement, the denouement, is maturation. Here the theme of the prior movement is broken down, and a stronger but slower variation is elaborated - adagio. The original clot is dissolved, and the collagen that was initially laid down is replaced with another version that increases the wound’s overall tensile strength. Granulation tissue, which makes up the wound healing bed, is replaced with a scar. Then the movement continues over months, with remodeling occurring on the cellular level, in a beautiful call-and-response between the cells and the extracellular matrix that they create and that surrounds them. After three months, the scar reaches its maximal tensile strength, just 80 percent that of unwounded skin. The immune cells go quiet, the wound repair process switches off, and the healing is complete.
