Apoptosis (Intrinsic, Extrinsic Pathways) vs. Necrosis
Summary
TLDRこのビデオスクリプトでは、細胞死の2つのタイプである壊死とアポトーシスの違いを比較しています。壊死は計画されておらず炎症を引き起こし、常に病理学的であるのに対し、アポトーシスはプログラムされた細胞死で、通常は生理的であり、時には病理学的になることがあります。スクリプトでは、アポトーシスの2つの経路である内源的経路と外源的経路について説明し、それぞれの経路における重要な分子の役割を解説しています。また、アポトーシスと壊死の重要なポイントを覚えやすくするための助けとなる記憶術も紹介されています。
Takeaways
- 😀 坏死(necrosis)和凋亡(apoptosis)是细胞死亡的两种不同方式,前者是非计划性的,后者是程序化的细胞死亡。
- 😀 坏死总是伴随炎症反应,而凋亡则通常不引起炎症。
- 😀 坏死是病理性的,而凋亡在正常情况下是生理性的,但在某些情况下(如癌症)也可能成为病理性的。
- 😀 坏死的细胞膜会被破坏,而凋亡的细胞膜始终保持完整。
- 😀 凋亡的内在途径涉及线粒体释放细胞色素C,激活半胱氨酸蛋白酶(caspases),导致细胞死亡。
- 😀 凋亡的外在途径涉及死亡受体如Fas或TNF受体的激活,导致启动子半胱氨酸蛋白酶的激活,最终也激活半胱氨酸蛋白酶。
- 😀 Bcl-2和Bcl-xl是抗凋亡因子,它们通过抑制线粒体释放细胞色素C来防止凋亡。
- 😀 凋亡的内在途径中,Bax和Bak是促凋亡信号分子,它们促进线粒体释放细胞色素C。
- 😀 坏死的类型包括凝固性坏死、液化性坏死、干酪性坏死、脂肪坏死、纤维素性坏死和坏疽。
- 😀 凝固性坏死常见于缺血,液化性坏死见于脓肿,干酪性坏死见于结核和真菌感染,脂肪坏死见于胰腺炎和乳腺损伤,纤维素性坏死见于血管炎,坏疽见于糖尿病足溃疡。
Q & A
細胞死の2つのタイプは何ですか?
-細胞死には壊死(necrosis)とアポトーシス(apoptosis)という2つのタイプがあります。
壊死の特徴は何ですか?
-壊死は計画されておらず、炎症を引き起こし、病理的であり、マクロファージによって消化されます。
アポトーシスが病理的になる状況とはどのような時ですか?
-アポトーシスは通常は生理的ですが、制御不能になり、例えばがんのような異常な細胞増殖が生じた時に病理的になります。
アポトーシスにおける2つの主要な経路は何ですか?
-アポトーシスには内在経路(intrinsic pathway)と外在経路(extrinsic pathway)の2つの経路があります。
内在経路におけるBAXとBAKの役割は何ですか?
-BAXとBAKはプロアポトーシック信号分子で、ミトコンドリアに作用してアポトーシスを促進し、細胞死を引き起こします。
Bcl-2とBcl-xLの機能は何ですか?
-Bcl-2とBcl-xLはアンチアポトーシック因子で、ミトコンドリアを抑制し、アポトーシスを防ぎます。
細胞質クロムCのリリースがアポトーシスにどのように関与するか説明してください。
-BAXとBAKが作用し、Bcl-2とBcl-xLが非活性化された場合、細胞質クロムCがミトコンドリアからリリースされ、カスパスを活性化し、細胞死を引き起こします。
アポトーシスにおけるカスパスの役割は何ですか?
-カスパスはアポトーシスの最終的な標的で、活性化されると細胞を制御されたプログラムされた方法で死滅させます。
外在経路におけるFas配列またはTNF受容体への結合はアポトーシスにどのように影響を与えるか説明してください。
-Fas配列またはTNF受容体への結合はイニシエータカスパスを活性化し、最終的に大カスパスを活性化して細胞死を引き起こします。
細胞毒性T細胞がアポトーシスにどのように関与するか説明してください。
-細胞毒性T細胞は膜に接着し、グランズメBを放出して膜を穿孔させ、ペルフォリンを活性化させ、カスパスを活性化して細胞死を引き起こします。
壊死の6つのタイプを教えてください。
-壊死の6つのタイプは凝固性壊死、液化性壊死、干酪状壊死、脂肪性壊死、フィブリノーイド壊死、壊疽性壊死です。
凝固性壊死が見られる疾患例は何ですか?
-凝固性壊死は多くの種類の虚血症で見られ、組織学的にはエオシンフィリアが特徴的です。
液化性壊死の特徴と疾患例は何ですか?
-液化性壊死は膿瘍などで見られ、組織学的にはニュートロフィル性デブリが特徴的です。
アポトーシスと壊死の違いを3つ挙げてください。
-1) 壊死は計画されておらず、アポトーシスは計画されています。2) 壊死は炎症を引き起こし、アポトーシスは炎症を引き起こしません。3) 壊死は常に病理的ですが、アポトーシスは通常は生理的ですが、制御不能になると病理的になります。
Outlines
🔬 細胞死の基本理解: 壊死とアポトーシスの違い
この段落では、細胞死の二つのタイプである壊死とアポトーシスの基本的な違いについて説明されています。壊死は計画されておらず、炎症を引き起こし、常に病理学的なものであるとされています。一方で、アポトーシスは細胞の死亡をプログラム化したものであり、通常は炎症を引き起こさないことが特徴です。また、壊死は常に病理学的であるのに対して、アポトーシスは制御された状態であれば正常であり、病理学的になるのは制御が逸脱した場合のみです。さらに、壊死ではマクロファージによって組織が消化されるのに対して、アポトーシスでは細胞膜が常に保持され、細胞が縮小して死ぬことがあります。これらの違いは、細胞死の理解において非常に重要であるとされています。
🌱 アポトーシスの内因性経路: 細胞死の制御
この段落では、アポトーシスの内因性経路について詳しく説明されています。内因性経路では、ミトコンドリアが重要な役割を果たしています。プロアポトーシック信号分子(バックス)はミトコンドリアに作用し、細胞死を促進する一方で、アンチアポトーシック因子(bcl-2、bcl-xl)はその作用を抑制します。バックスが活性化すると、ミトコンドリアからシトクロームCが放出され、カスパスを活性化し、細胞死を引き起こします。一方、bcl-2やbcl-xlが活性化すると、シトクロームCの放出が抑制され、細胞死は起こりません。この経路は、細胞が損傷を受けた場合にプログラム化された細胞死を促進するため、正常な生理的プロセスとして機能します。
🔍 アポトーシスの外因性経路: 細胞死の誘導
この段落では、アポトーシスの外因性経路について説明されています。外因性経路では、細胞表面の受容体に結合する配列(Fas ligandやTNF-alpha)が重要な役割を果たします。これらの配列が受容体に結合すると、初期カスパス(イニシエーターカスパス)が活性化され、最終的には大カスパス(エフェクターカスパス)を活性化し、細胞死を引き起こします。外因性経路は、細胞毒性T細胞による細胞死の誘導にも関与しており、細胞毒性T細胞が細胞表面に結着すると、グランズイムBを放出し、細胞膜を穿孔させてペルフォリンを放出します。ペルフォリンはカスパスを活性化し、細胞死を促進します。この経路は、細胞が適切に死亡するプロセスを制御する上で重要な役割を果たしています。
🏥 壊死のタイプ: 病理学的変化の概要
この段落では、壊死の異なるタイプについて概要を説明されています。壊死は、細胞膜が破壊されることで特徴づけられており、炎症を引き起こし、病理学的変化をもたらします。壊死のタイプには、凝固性壊死、液化性壊死、干酪性壊死、脂肪性壊死、フィブリノーイド壊死、壊疽性壊死があります。それぞれのタイプは、特定の病理的状況や組織の外観に基づいて識別されます。例えば、凝固性壊死は、多数のイソシアン酸染色で赤色に染まる組織を特徴としており、缺血症でよく見られます。液化性壊死は、脓胞症で見られ、中心にはニュートロフィル性デブリが含まれています。これらのタイプは、細胞死の病理学的変化を理解する上で重要な役割を果たしています。
📚 総括: 壊死とアポトーシスの高得点サマリー
最後の段落では、壊死とアポトーシスの高得点サマリーが提供されています。アポトーシスは、細胞死の重要なトピックであり、内因性経路と外因性経路の両方について理解することが求められます。アポトーシスは、細胞のプログラム化された死亡であり、細胞毒性T細胞やシグナル分子によって誘導されます。一方、壊死は、細胞膜の破壊によって引き起こされ、炎症を伴い、病理学的変化をもたらします。この段落では、これらの概念を簡潔にまとめ、試験や複雑なテキストを理解するための助けとなる情報を提供しています。
Mindmap
Keywords
💡坏死(necrosis)
💡凋亡(apoptosis)
💡内在途径(intrinsic pathway)
💡外在途径(extrinsic pathway)
💡细胞色素C(cytochrome C)
💡半胱氨酸蛋白酶(caspases)
💡Bax和Bak
💡Bcl-2和Bcl-xL
💡滤泡性淋巴瘤(follicular lymphoma)
💡颗粒酶B(Granzyme B)和穿孔素(Perforin)
Highlights
坏死和凋亡的区别是医学考试中的重要主题。
坏死是非计划性的,而凋亡是程序化的细胞死亡。
坏死总是引起炎症,而凋亡则不引起炎症。
坏死总是病理性的,而凋亡有时是病理性的。
坏死的细胞膜总是被破坏,而凋亡的细胞膜保持完整。
凋亡是程序化的,通常是一件好事,但失控时可能变得病理性。
坏死是由巨噬细胞消化最终被破坏的组织。
凋亡细胞的死亡是由于线粒体释放促凋亡因子。
凋亡的内在途径和外在途径是凋亡的两个主要途径。
Bax和Bak是促凋亡信号分子,而Bcl-2和Bcl-xl是抗凋亡因子。
Bax和Bak激活线粒体释放细胞色素C,激活caspases导致细胞死亡。
Bcl-2和Bcl-xl抑制凋亡,防止细胞色素C释放和caspases激活。
凋亡的外在途径可以通过Fas配体或TNF-alpha激活。
细胞毒性T细胞释放的颗粒酶B可以激活穿孔素,进而激活caspases。
凋亡的外在途径最终也导致caspases的激活和细胞死亡。
凋亡的内在途径的助记方法是“broccoli”,代表Bcl-2抑制凋亡。
凋亡的外在途径的助记方法是“toxic granny perf”,代表细胞毒性T细胞、颗粒酶B和穿孔素。
坏死的类型包括凝固性坏死、液化性坏死、干酪性坏死、脂肪坏死、纤维素性坏死和坏疽。
凝固性坏死常见于缺血,液化性坏死常见于脓肿。
干酪性坏死见于结核病和真菌感染,脂肪坏死见于胰腺炎和乳腺损伤。
纤维素性坏死见于血管炎,坏疽见于糖尿病足溃疡。
Transcripts
when we talk about the difference
between necrosis and apoptosis there are
some general themes that I think you
should keep in mind when you're sitting
for USMLE and comlex let's talk about
some differences necrosis is not planned
whereas apoptosis is programmed cell
death necrosis is always inflammatory so
it's marked by inflammation and swelling
of tissue apoptosis however is not
inflammatory necrosis is always
pathological no matter what type of
necrosis it is it's always pathological
but apoptosis is only sometimes
pathological so because it's programmed
and the body's intending for certain
cells to die that's a good thing
but if that goes out of control and you
have some type of mutation which we'll
get into and develop some type of cancer
which we'll get into that's when
apoptosis can become pathological but to
summarize necrosis is always
pathological and apoptosis is normally
it's a good thing but when it gets out
of control then it becomes pathological
so more differences necrosis is marked
by macrophage digestion of the ultimate
tissue that gets destroyed
whereas apoptosis cells die because of a
release of a pro-apoptotic factor from
the mitochondria in necrosis the cell
membrane is always destroyed and in
apoptosis the cell membrane always stays
intact even when the shell the cell
shrinks up and dies so these are some
very broad differences and if there's a
theme that you're noticing here it's
that necrosis is noxious and we're gonna
remember apoptosis and I'll get more
into that later when I talk about what
apoptosis actually is and the different
pathophysiology is behind them but
necrosis is noxious which is to say that
necrosis is bad look at look at the
themes here it's not planned it's it
marked by inflammation always
pathological things are being digested
by macrophages and we're destroying cell
membranes those are all bad and kind of
extreme terms when it comes to killing
tissue but apoptosis on the other hand
is programmed so it's intended it's not
inflammatory it's usually a good thing
only sometimes as a pathological
it's pretty well controlled in terms of
pro-apoptotic factors being released
from the mitochondria and the cell
membranes are always intact
even after the cells died after you have
the death of shrinkage of cells your
cell membrane still is intact so this is
a pot Moses and I'll get more into this
mnemonic later but think about Moses as
a religious figure being a good person
who's very like purposeful and
programming and thinking about what he's
doing
that's apoptosis but necrosis is always
not just now I want to talk about
apoptosis because it's a very
complicated topic it's got multiple
pathways there's a lot of physiology
that you need to know here and I'm gonna
simplify all of this for you so the
first thing we're gonna do is talk about
the intrinsic pathway there's two
pathways in apoptosis there's the
intrinsic pathway and the extrinsic
pathway so let's start with the
intrinsic pathway what you see here is a
mitochondria and depending on which
molecule is signaling to the
mitochondria that determines whether or
not we proceed through apoptosis and
perform programmed cell death so on the
left side of the mitochondria you see
backs and back these are pro-apoptotic
signal molecules which is to say that
when these act on the mitochondria they
promote apoptosis and lead to programmed
cell death on the other side you see
bcl-2 and bcl-xl and these are anti a
platonic factors which is to say that if
bcl-2 or bcl-xl are active they inhibit
the mitochondria and prevent apoptosis
so right off the bat those are some
themes that you need to understand now
if we're talking about backs and back
what happens is these signal the
mitochondria to release something from
pores in the side of the mitochondria
which you see here shown as black
circles and what gets released if backs
and back are acting on the mitochondria
and bcl-2 and bcl-xl are inactive which
means they cannot act on the
mitochondria then you get the release of
something called cytochrome C and when
cytochrome C spills out of the
mitochondria it activates something
called caspases and caspases are the end
target of apoptosis when a caspase gets
activated it causes cell death
it kills the cell in a controlled
programmed way so again to summarize
here Backson back activate the
mitochondria to release cytochrome C
through the pores in the side of the
mitochondria so
see activates cat faces and caspases
killed the cell so this is normal this
is what the body wants because again
apoptosis is programmed cell death so if
a cell gets injured by something like
radiation if you're out on the beach too
long and don't wear sunscreen you need
to kill the cells because if the cell
gets damaged it can grow out of
proportion and cause cancer so this is
why in many situations programmed cell
death is a good thing and again
apoptosis we think of a pot Moses
because it's a good thing it's a
religious figure it's someone who's very
prominent the other reason that I use a
pot Moses as our new moniker is because
Backson back when they activate the
mitochondria they open those pores which
is to say they part the sea just like
Moses did allowing room for cytochrome C
to spill out of the mitochondria cross
the river and do its job by performing
programmed cell death so that's what
happens when backs and back activate
apoptosis but what happens if VCL 2 and
B see it bcl-xl are the ones that are
activated well in this case what happens
is you never get the release of the
cytochrome C from the side of the
mitochondria and when that happens you
cannot activate cytochrome C so you
cannot activate caspases so you do not
get cell death and instead of cell death
you get in appropriate amounts of cell
survival so if too many cells are not
dying they're living and what happens is
they grow out of control so if you have
a mutation where bcl-2 becomes over
activated which is to say that it's
completely preventing programmed cell
death and cells are growing out of
control that's follicular lymphoma and
you may have memorized without even
realizing that follicular lymphoma is a
translocation between chromosome 14 and
18 which over activates bcl-2 because
bcl-2 gets over activated in that
translocation so think about it guys if
you just brutally memorized that
follicular lymphoma causes bcl-2 to get
translocated and therefore activated
what did that actually mean well bcl-2
prevents apoptosis prevent cytochrome C
prevents caspase activation prevents
cell death so cells grow out of control
and you get cancer you get follicular
lymphoma because cells aren't dying
they are multiplying so that's the
intrinsic pathway of apoptosis and the
high-yield summary is shown here backs
in back cause apoptosis by activating C
and then caspases bcl-2 and bcl-xl
inhibit apoptosis and never let that
happen so the end result here is
activation of caspases which causes
apoptosis
that's the intrinsic pathway now let's
talk about the extrinsic pathway and
when I'm done with the physiology on
this side we'll wrap up with some
mnemonics for both of these pathways so
in the intrinsic pathway you can have
binding of one of two molecules or both
to activate the extrinsic pathway and
they are shown here fast ligand can bind
to the fast receptor or TNF alpha can
bind to the TNF receptor in either of
these situations whether it's one or
both you get the activation of something
called initiator caspases and these are
basically like baby cat spaces that then
go on to activate the Big Daddy cat
space and again when the Big Daddy cat
space is activated it causes cell death
so this is the extrinsic pathway now the
tricky think about the extrinsic pathway
and why it's really kind of hard to
memorize for USMLE and comlex is that
there's actually two different ways that
the extrinsic pathway can be activated
it can be through the fast ligand
tnf-alpha binding or it can be through
the active the activity of a cytotoxic T
cell so if a cytotoxic T cell comes up
and latches onto a membrane it can
release something called grands ib and
grands i'm be literally perforates a
membrane and allows the release of
something called per foreign so grant
time B breaks through this membrane and
per foreign enters the cell and when per
foreign enters the cell per foreign goes
on to activate caspases and if you're
not already seeing this theme whenever
you activate a cash base it causes cell
death programmed cell death that is to
say it causes apoptosis so whether
you're in the intrinsic pathway and you
use cytochrome C to activate caspases
or you're in the extrinsic pathway and
you bind fast lag in too fast or
tnf-alpha to the TNF receptor where the
cytotoxic T cells spits out grands I
mean be that perforates in the membrane
that activates per forum
all of these things activate caspases
which cause apoptosis so if you're with
me so far you already know the
physiology of apoptosis you know how
this works now let's give you some sexy
mnemonics to make this easier so when
we're talking about the intrinsic
pathway our mnemonic is gonna start with
B CL now the way that we're gonna
remember that b CL to inhibit apoptosis
which causes cell death to not happen is
we write out the word b CL as you see
here in red text and we're gonna add
some letters to be Co we're gonna make
it into the word broccoli so B CL is
still there we just added some letters
and what does broccoli do it keeps you
alive you live longer if you eat
broccoli just like broccoli or B CL
bcl-2 will make the cells live longer
and it'll keep them alive it inhibits
apoptosis but what about the extrinsic
pathway where is the sexy pneumonic for
that well let's talk about that so in
the entry extrinsic pathway I need you
to remember that cytotoxic C's T cells
release grams I'm B which perforates
membranes activates perforin
which activates cat phases I know that
can seem like a lot so how are you gonna
remember this let's write out some words
that represent each step in this
mechanism so toxic for the cytotoxic T
cell granny for the Grands i'm b and
perf for per foreign so what happens if
you're really really toxic in front of
your grandmother you'll cause her to
perf your calls her to get really really
mad maybe even have a stroke if you're
not careful so don't be toxic to granny
and call sort of perf that's the
extrinsic pathway if you're toxic you'll
make granny perf toxic for cytotoxic T
cell granny for Gran's iron B and
perfect for perforin again all of these
pathways intrinsic or both of the
different types in extrinsic they all
end with caspases causing cell death I
really don't think it's that tough to
remember but if you're with me so far
you are a master of apoptosis and you'll
be able to answer any question that they
throw on you throw at you on us Emily or
complex that's apoptosis not as bad as
some of the textbooks make it sound
right let's move on to necrosis and
quickly summarize the different types of
necrosis now necrosis
admittedly admittedly a lower yield
topic than apoptosis and because of that
I'm gonna quickly go through this table
that's gonna summarize everything you
need to know there are six different
types of necrosis that are technically
fair game for boards coagulative liqui
fact of caseous fat necrosis fibrin oyd
necrosis and gangrenous in each of these
I'm going to give you an example of
where you'll see this type of necrosis
I'm gonna tell you what you'll see on
the histology and then I'm gonna give
you my sexy dirty to USMLE mnemonics
remember this this is really really easy
and and a little lower yield than
apoptosis so we're gonna move through
this quickly so for coagulative necrosis
you see this in most types of ischemia
not all types of ischemia but like 90%
of it so if it's this enix quemic event
that you're seeing on your test and you
have to take a guess pick coagulative on
histology you'll see yoson ophelia so
they'll use an ESN stain and you'll see
a lot of eosinophils and the pneumonic
here is coagulation because think about
it if you have a problem with
coagulation then that's where you have
ischemia and ischemia is coagulative
necrosis and craig Latif has Co AG
literally in the name so problems with
your coagulation cascade cause ischemia
the example of coagulative necrosis is
ischemia and then you just got to
memorize eosinophilia so I took out you
know a lot of the the difficulty in
memorizing here in liqui fact if you see
this in abscesses so abscesses
classically and histology have
neutrophilic debris inside of them and
the mnemonic here is liquid fact if so
instead of saying liqui fact it's a
liquid effective because if you've ever
seen an abscess before the center of it
is filled with neutrophilic debris but
but it's pus right it's liquid so if you
don't know what an abscess looks like
Jesus google it because you're gonna see
a lot of them in your career but
abscesses are filled with liquid pus
neutrophilic debris that's liquid fact
if aka liqui fact of necrosis caseous
you see in tuberculosis and in fungal
infections on histology you see
lymphocytes and macrophages forming
granulomas so the pneumonic here for
Casey is instead of saying Casey s I
want you to say cheesiest because fungal
infections you might say that they look
a little cheap
if you've ever seen them they'll have
this like cheese like quality to them so
cheesiest reminds me of caseous and i
tie that back into tibi and fungi
because fungal infections look cheesy
sometimes and then if you know anything
about tuberculosis you already know
about the granulomas on histology so you
should know that lymphocytes and
macrophages are gonna be present moving
on fat necrosis this is in pancreatitis
it's also in trauma to the breast and
women histology you'll see
saponification and complexing with
calcium and the pneumonic here there
really isn't one it's just the name fat
around the pancreas you have lots of fat
deposition around female breasts you
have lots of fat depositions so breast
trauma is fat necrosis and pancreatitis
is fat necrosis so I just remember the
word fat which reminds me of the organs
that classically have a lot of fat
that's fat necrosis the last two I'm
gonna group together here because
they're the two lowest yield on this
chart
fibrin necrosis you see in any type of
vasculitis
you see fibrin thickening of the vessels
so fibrin oeid literally has fibrin in
the name so there's no mnemonic for this
one gangrenous you see this in distal
extremity ulcers like diabetic foot
ulcers on histology this is a
combination of coagulative necrosis plus
liquefaction so you'll see a little bit
of you of Cinna philia you'll see a
little bit of that neutrophilic debris
and the pneumonic here also really easy
it's gangrene and so you know people
refer to gangrene like it's a medical
process and technically when someone
says gangrene what they actually mean to
say is gangrenous necrosis but of course
laypeople don't use that term but if you
know what gangrene looks like or can
imagine someone having gangrene or
gangrenous necrosis on the bottom of
their foot that is the mnemonic for
remembering gangrenous necrosis but
again this chart is a summary a little
bit lower yield apoptosis is definitely
the big topic in this video but no
coagulative liqui fact of caseous and
fat and if then if you have the memory
available throw in fibrin and gangrenous
but that's it guys that's apoptosis
versus necrosis high-yield summary of
everything that you need to know and
absolutely nothing more I really hope
that this was helpful
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