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Фибринолиз что это такое

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  1. ИНГИБИТОРЫ ФИБРИНОЛИЗА
  2. Ингибиторы фибринолиза (антифибринолитики)
  3. Посмертная или фибринолизная кровь
  4. Свертывание крови и фибринолиз
  5. Фибринолиз
  6. Фибринолиз
  7. ФИБРИНОЛИЗИН (ПЛАЗМИН) фл. 20.000 ЕД, содержимое флакона

Вторичные антикоагулянты

Первичные антикоагулянты

Противосвертывающая система крови

Антикоагулянты (блокируют разные фазы свертывания кро­ви).

Первичные антикоагулянты имеются в крови до начала свер­тывания:

• антитромбин III (в основном образуется в эндотелии и в печени) — плазменный кофактор гепарина. При отсутствии гепарина его активность уменьшается в 700 раз. В активной фор­ме составляет 90 % всей антитромбиновой и 70 % антикоагулянтной активности крови. Ингибирует тромбин (фактор Па), а также факторы Ха, IXa, XIa (специфическим ингибитором тромбина является пептид гирудин, образуемый пиявками);

• гепарин (сульфатированные полисахариды, образуются тучными клетками особенно печени и легких) образует ком­плекс с антитромбином III, превращая его в активный анти­коагулянт. В малых концентрациях ингибирует образование протромбиназы (фазу I), в высоких концентрациях тормозит все три фазы коагуляции, активирует фибринолиз. Комплекс «гепарин + антитромбин III» может фиксироваться на мемб­ране эндотелиальных клеток, обеспечивая тромборезистентность сосудистой стенки;

• a1-антитрипсин ингибирует тромбин (Па), факторы ХПа, IXa, XIa;

• протеин С (сериновая протеаза, образуется в печени с участием витамина К) инактивирует факторы Va, VIII, уско­ряет фибринолиз. Сам активируется тромбином, протеином S, тромбомодулином;

• тромбомодулин (образуется в эндотелии) блокирует рецепторы для тромбина на эндотелиоцитах, активирует про­теин С;

• антитромбопластины ингибируют факторы III и VIIa.

Вторичные антикоагулянты образуются в процессе сверты­вания крови и фибринолиза:

• атитромбин I — это фибрин, который адсорбирует и инактивирует тромбин, факторы Va, Ха;

• антитромбин VI — это продукты фибринолиза, ко­торые блокируют фибриноген и фибрин-мономер, тромбин и фактор XIa.

Фибринолиз (препятствует образованию и осуществляет лизис фибрина тромба, образующегося в процессе постоянного локального гемостаза, может осуществляться по двум вариантам: с уча­стием плазмина и без участия плазмина).

Плазминовый вариант фибринолиза:

• осуществляется в две фазы (рис. 3.3):

♦ в первой фазе плазменный профермент плазминоген пре­вращается в активную сериновую протеазу — плазмин. Плаз­миноген — одноцепочечный гликопротеин, образуемый в печени, костном мозге, почках и других органах; концент­рация в плазме 0,2 г/л. Он имеет лизинсвязывающие участ­ки, через которые присоединяется к фибрину (высокое срод­ство) и фибриногену (низкое сродство), поэтому в норме всегда входит в состав образующегося фибринового тромба. В его активации участвуют:

■ тканевые активаторы плазминогена: сериновые протеазы из клеток разных тканей (например, урокиназа по­чек, фактор Р8 тромбоцитов, протеазы нейтрофилов) и эндотелия их сосудов;

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■ плазменные активаторы плазминогена: фактор ХПа, калликреин (XlVa), факторы комплемента С8 и СЗ, про­теин С и др.;

■ экзогенные вещества: стрептокиназа стрептококков, ле­карства;

♦ во второй фазе образовавшийся плазмин расщепляет фиб­рин тромба (по пептидным связям Лиз—-Apr и Лиз—Лиз) до пептидов и аминокислот (продукты деградации фибрина);

♦ сс2-антиплазмин (гликопротеин, синтезируется в пече­ни) — самый активный ингибитор фибринолиза, образует прочные комплексы с плазмином, лишая его фермента­тивной активности, и с фибрином, делая его нечувстви­тельным к плазмину;

♦ a2-макроглобулин (гликопротеин) оказывает более мед­ленное, но длительное ингибирующее действие на плаз-мин, образуя с ним ковалентный комплекс;

♦ a1-антитрипсин (синтезируется в печени) оказывает мед­ленное ингибирующее действие на плазмин (быстрое — на трипсин).

Неплазминовый вариант фибринолиза

Неплазминовый вариант фибринолиза осуществляется фибринолитическими протеазами лейкоцитов, тромбоцитов, эритроцитов и ан­титромбином III в комплексе с гепарином, которые могут непосред­ственно расщеплять фибрин.

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Фибринолиз (от Фибрин и греч. lýsis – разложение, растворение) — процесс растворения тромбов и сгустков крови, неотъемлемая часть системы гемостаза, всегда сопровождающая процесс свертывания крови и культивирующаяся факторами, принимающими участие в данном процессе. Является важной защитной реакцией организма и предотвращает закупорку кровеносных сосудов сгустками фибрина. Также фибринолиз способствует реканализации сосудов после прекращения кровотечения.

Включает в себя расщепление фибрина под воздействием плазмина, присутствующего в плазме крови в виде неактивного предшественника — плазминогена. Последний активируется одновременно с началом процесса свертывания крови.

Содержание

Внутренний и внешний путь активизации [ править | править код ]

Фибринолиз, как и процесс свертывания крови, протекает по внешнему или внутреннему механизму. Внешний путь активации осуществляется при неотъемлемом участии тканевых активаторов, синтезирующихся преимущественно в эндотелии сосудов. К данным активаторам относят тканевый активатор плазминогена (ТАП) и урокиназу.

Внутренний механизм активации осуществляется благодаря плазменным активаторам и активаторами форменных элементов крови — лейкоцитов, тромбоцитов и эритроцитов. Внутренний механизм активации разделяют на Хагеман-зависимый и Хагеман-независимый. Хагеман-зависимый фибринолиз происходит под влиянием фактора XIIа свертывания крови, калликреина, которые вызывают превращение плазминогена в плазмин. Хагеман-зависимый фибринолиз происходит наиболее быстро и носит срочный характер. Его основным назначением является очищение сосудистого русла от нестабилизированного фибрина, который образуется в процессе внутрисосудистого свертывания крови.

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Хагеман-независимый — осуществляется под влиянием протеинов C и S

Ингибирование фибринолиза [ править | править код ]

Фибринолитическая активность крови во многом определяется именно соотношением ингибиторов и активаторов процесса фибринолиза.

В плазме крови находятся также ингибиторы фибринолиза, подавляющие его. Одним из важнейших таких ингибиторов являются α2-антиплазмин, который вызывает связывание плазмина, трипсина, калликреина, урокиназы, тканевой активатор плазминогена. Таким образом препятствуя процессу фибринолиза на его ранних и на поздних стадиях. Сильным ингибитором плазмина является также α1-протеазный ингибитор. Также фибринолиз тормозится альфа2-макроглобулином, C1-протеазным ингибитором,и целым рядом ингибиторов активатора плазминогена, вырабатываемых в эндотелии, а также фибробластами, макрофагами и моноцитами.

Регуляция фибринолиза [ править | править код ]

Между процессами свертывания крови и фибринолизом в организме поддерживается равновесие.

Усиление фибринолиза обусловлено повышением тонуса симпатической нервной системы и поступлением в кровь адреналина и норадреналина. Это вызывает активацию фактора Хагемана, что запускает внешний и внутренний механизмы продукции протромбиназы, а также стимулирует Хагеман-зависимый фибринолиз. Из эндотелия также происходит выделение тканевого активатора плазминогена и урокиназы, стимулирующих процесс фибринолиза.

При повышении тонуса парасимпатической нервной системы наблюдаются также ускорение свертывания крови и стимуляция процесса фибринолиза.

Основным эфферентным регулятором процессов свертывания крови и фибринолиза является сосудистая стенка.

Литература [ править | править код ]

Физиология человека. Под ред. Покровского В.М., Коротько Г.Ф М.: Медицина, 1997; Т1 — 448 с., Т2 — 368с

См. также [ править | править код ]

Физиология человека. Учебник/Под ред. В. М. Смирнова.- М.: Медицина, 2002. — 608 с.: ил.(Учеб. лит. Для студентов мед. вузов). ISBN 5-225-04175-2 (стр. 231)

Фибринолиз — это процесс расщепления фибринового сгустка, в результате которого происходит восстановление просвета закупоренного тромбом сосуда. Фибринолиз начинается одновременно с ретракцией сгустка, но идет медленнее. Это тоже ферментативный процесс, который осуществляется под влиянием протеолитического фермента — плазмина (фибринолизина).

Плазмин находится в плазме крови в неактивном состоянии в виде плазминогена. Плазминоген синтезируется в печени, костном мозге, почках и других органах. Под влиянием кровяных и тканевых активаторов осуществляется его активация — переход в плазмин. Плазмин расщепляет фибрин на отдельные полипептидные цепи, в результате чего происходит лизис (растворение) фибринового сгустка (рис.4)

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Рис.4. Фибринолиз

Активация плазминогена, как и образование протрамбиназы, может протекать по внешнему и внутреннему путям. Внешний путь активации плазминогена осуществляется с помощью тканевых активаторов. К ним относятся в первую очередь тканевой активатор плазминогена (t -РА), который продуцируется эндотелиальными клетками разных тканей и находится главным образом в стенках кровеносных сосудов (преимущественно в венах и венулах), и урокиназа (и — РА), синтезируемая преимущественно почками и фибробластами. Тканевой активатор плазминогена принимает участие в растворении фибрина, находящегося в плазме. Урокиназа участвует в растворении фибрина, расположенного на поверхности клеток, в том числе эндотелиальных. Во внутреннем пути активации плазминогена участвуют кровяные активаторы, например, активированный фактор Хагемана, каллликреин, протеины С и S. Способностью активировать плазминоген обладают и некоторые экзогенные вещества, например, стрептокиназа стрептококков, некоторые лекарства.

В плазме крови находятся и физиологические ингибиторы фибринолиза. Одни ингибиторы (активаторы) нейтрализуют действие активаторов плазминогена, другие (антиплазмины) угнетают сам плазмин. Среди антиактиваторов выделено 3 типа ингибиторов. Антиплазминовым действием обладают б2— антиплазмин (б2-глобулин) и б2-макроглобулин. В первую очередь плазмин инактивируется б2— антиплазмином, способным нейтрализовать 2/3 всего плазмина, который может образоваться в крови из имеющегося плазминогена. Поэтому он быстро исчезает из кровотока и оказывает свое влияние местно в сгустке крови. При чрезмерном образовании плазмина может произойти истощение б2— антиплазмина. Тогда в ингибирование включается б2-макроглобулин, который является менее специфичным ингибитором плазмина. К ингибитором плазминогена относится и б1— антитрипсин.

Существует и неплазминовый вариант фибринолиза, который осуществляется фибриеолитическими протеазами лейкоцитов, тромбоцитов, эритроцитов и антитромбином III в комплексе с гепарином, которые могут непосредственно расщеплять фибрин. Все вещества, принимающие участие в процессе фибринолиза, объединены фибринолитическую систему. Кроме растворения сгустков крови и удаления отложений фибрина компоненты фибринолитической системы принимают участие и в других физиологических процессах: заживлении ран, регуляции роста, деления и миграции клеток, регенерации мышц, росте аксонов нейронов, процессах овуляции, оплодотворения и др. Процесс фибринолиза длится несколько суток и его результатом является реканализация сосуда, т.е. восстановление его проходимости. Ретракцию кровяного сгустка и фибринолиз выделяют как дополнительные фазы свертывания крови. Подчеркнем, что существующие два вида свертывания приводят к образованию двух видов тромбов — тромбоцитарного и плазменного.

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