Skin flap physiology

皮瓣制备过程造成的物理损伤以及对血管神经的损伤将对皮瓣产生刺激，而皮瓣对这些刺激的反应以及是否能够存活，将受其解剖以及生理特性的影响。

• 流向皮肤的血供主要有两个功能：提供营养和调节体温。调节体温功能的血流量可有相当大的变化范围：正常体温下，参与体温调节的血流量是提供营养需求的血流量的10倍左右；在皮肤血管完全扩张的情况下，血流量可在此基础上增加7倍；而在极低温度下，流向皮肤的血流量可能仅能满足其营养需求
• 位于真皮网状层的营养毛细血管网（nutrient capillary network）以及位于乳头层的动静脉短路（arteriovenous shunts）行使着上述两大功能。 The amount of blood flow to the skin depends ultimately on arteriolar pressure and flow. Under conditions of adequate systemic vascular pressure, however, arterioles act as preshunt and precapillary sphincters that regulate the flow through each vascular network. The sphincters in the two vascular systems respond to different stimuli. The precapillary sphincter, which controls the amount of nutritive blood flow to the skin, responds to local hypoxemia and increased metabolic byproducts by dilation. The preshunt sphincters are involved in regulating the changes in blood flow that affect thermoregulation and systemic blood pressure. Release of norepinephrine by the postganglionic sympathetic fibers results in contraction of the preshunt sphincters.
• Vasodilation can also occur with excessive body temperature. Local release of acetylcholine by sympathetic nerve fibers may cause vasodilation by directly affecting vasodilator fibers or acting through the release of the potent vasodilator bradykinin（缓激肽） from the sweat glands. The cutaneous circulation is also extremely sensitive to circulating norepinephrine and epinephrine. Even in areas of skin that have lost their sympathetic innervation, a mass discharge of the sympathetic system will still result in intense vasoconstriction in the skin.

血液流经微循环的通路有三条。
1.迂回通路指血液经微动脉、后微动脉、毛细血管前括约肌、真毛细血管网到微静脉的通路。真毛细血管管壁薄、通透性好，穿插于细胞间隙中，迂回曲折，相互交错成网，血流缓慢，血管轮流交替开闭，是血液与组织细胞进行物质交换的主要场所，故又称为营养通路。

2.直捷通路指血液经微动脉、后微动脉、通血毛细血管到微静脉的通路。它经常处于开放状态。由于血流速度快，流经通血毛细血管时很少进行物质交换。这条通路的主要生理意义在于使部分血液迅速通过微循环及时回心。

3.动-静脉短路指血液经微动脉、动-静脉吻合支进入微静脉的通路。吻合支管壁厚，不能进行物质交换，又称为非营养通路，且经常处于关闭状态。皮肤的这条通路有调节体温的作用。当气温升高时，通路开放，使流经皮肤血量增多而有利散热；气温下降，通路关闭而利于保存热量。感染性或中毒性休克病人，这条短路将大量开放，虽然可使流经微循环的血液迅速回心，但血液不经过真毛细血管网，导致组织缺血、缺氧更加严重。

neurovascular supply to local skin flaps

• Blood vessels travel by one of two main routes to terminate in the cutaneous circulation:
  • 肌皮动脉
  • 肌间隔血管
• 皮肤的神经主要是感觉神经和交感神经. 二者分布区域及方式有区别：The sensory nerves are distributed in segmental fashion, forming dermatomes, and participate in the skin’s protective function. The postganglionic terminals of cutaneous sympathetic nerves contain the neurotransmitter orepinephrine and are found in the area of cutaneous arterioles

vascular design of common local skin flaps in the head and neck

• random cutaneous flap, 长宽比例反映了不同区域的血供情况，但是更宽并不意味着可以更长，对此后面会有讲述；
• arterial cutaneous flap. Flap necrosis secondary to ischemia can be said to occur only in the random portion of the flap.

physiologic changes afte skin flap elevation

• 决定皮瓣能否存活的因素是血供：能否满足皮瓣存活所需的最小营养血供。影响皮瓣存活的其他因素也主要是通过影响皮瓣血供发生作用。皮瓣制备的过程及成型以后主要会发生以下变化

Impairment of vascular supply

• 皮瓣制备过程中对皮瓣最主要的损伤来自于对血供的损伤。This interruption results in a local decrease in perfusion pressure to the skin.
• 在随意皮瓣中，基底更宽并不意味着皮瓣可以更长。随意皮瓣的长度是由血管本身的特性（血管内阻力，intervascular resistance）以及灌注压决定的（perfusion pressure）。当灌注压低于皮下血管丛内微动脉的最低灌注压（critical closing pressure of the arterioles）时，皮瓣将缺乏足够的营养血供从而发生坏死。皮瓣基地更快固然可以纳入更多供血血管，但是这些增加的血管的灌注压和之前买的血管是一样的，即增加血管数量并没有增加灌注压，灌注压不足仍然不能保证足够的营养血供，即不能延长皮瓣长度。(Milton, S. H. (1970). “Pedicled skin-flaps: the fallacy of the length: width ratio.” Br J Surg 57(7): 502-508.)

• 皮瓣耐缺血时间的研究：Myers has emphasized that “fresh flaps are always both viable and ischemic.”12 Depending on the degree of ischemia and the amount of time before recovery of nutrient blood flow, the flap will either die or recover. In the pig model, arterial and random flaps can tolerate an average of 13 hours of total avascularity and remain viable. In flaps with reduced perfusion, this time is probably much longer.
• 静脉回流障碍比动脉血供受损对于皮瓣的危害更大，对于皮瓣而言，保留皮下血管丛的以能提供足够的静脉回流，但是保留蒂部的伴随静脉仍然是至关重要的。
• 对于淋巴管的损伤也会引起间质内液压增加，随后出现的水肿可增加血管内阻力从而影响血管丛灌注能力。

Nerve section

• denervation of a skin flap postpont neovascularizaton of the skin flap.
• 交感神经损伤导致的局部“高肾上腺素能状态”会影响皮瓣血供：When a sympathetic nerve is divided, catecholamines are released from the nerve terminal and the mechanism for catecholamine reuptake is eliminated. A local “hyperadrenergic state” develops that produces vasoconstriction mediated by alpha-adrenergic receptors in the cutaneous vasculature. The stored transmitter is depleted within 24 to 48 hours.
• severe sympathetic denervation contributes to the production of oxygen free radicals, which may exert their inhibitory effects on neovascularization.

inflammation and prostaglandins

reperfusion(free radicals)

Attempts to alter skin flap viability

skin flap delay

• Four concepts are accepted concerning the delay phenomenon. First, it requires surgical trauma. Second, a large percentage of the neurovascular supply to the flap must be eliminated. Third, delay results in increased flap survival at the time of tissue transfer. Fourth, the beneficial effects can last up to 6 weeks in the human. To explain this phenomenon, three theories regarding the mechanism of delay have been developed: (1) delay improves blood flow, (2) delay conditions tissue to ischemia, and (3) delay closes arteriovenous shunts. Most recent papers support a mechanism resulting in increased circulation to the flap.
  
• Cytokines may be a mechanism by which surgical delay can increase flap survival. Basic fibroblast growth factor (bFGF) and VEGF expressions increased significantly after delay.

increase of blood supply

• indirect vasodilators: “pharmocologoc daley”
• direct vasodilators
• neovascularization
• flap prefabrication
• alter of rheology
• Inflammation and Prostaglandins
• tissue expansion

prolonged viability

• protection against harmful agents
• nitric oxide
• increased tolerance of ischemia
  • increased oxygenation
  • metabolic management

Impaired flaps

• 烟草对皮瓣存活的影响：
  • The deleterious effects of nicotine appear to increase with prolonged exposure.
  • The mechanism whereby tobacco or nicotine lowers flap survival is believed to be direct endothelial damage or vasoconstriction secondary to catecholamine release or local concentrations of prostaglandins.
  • Smoking impairs flap healing by causing vasoconstriction from nicotine and increased levels of carboxyhemoglobin, which limits oxygen delivery. In addition, smoking decreases neutrophilic function and decreases collagen synthesis.
• inspite of prior irradiation, the delay phonomenon does improve flap survival, flap neovascularization is delayed but not eliminated after irradiation. the use of angiogenic growth factors has the potential to increase the viability of irradiated skin flap by means of accelerating revascularization.

Tissue engineering

In using gene therapy to improve flap survival, various methods have employed plasmids or viruses to transplant genes that code for and produce growth factors in ischemic tissue.