Stroke Pathogenesis (with a focus on Ischemic Stroke)

Summary

In this video from the Calgary Guide series, the pathogenesis of stroke is discussed, focusing on the four main types: acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and venous sinus thrombosis. The video explains the causes and mechanisms behind each type, emphasizing how they lead to impaired blood supply and symptoms in the brain. A detailed discussion of acute ischemic stroke is also included, highlighting its causes and effects on cerebral blood flow, neuronal damage, and inflammation. Viewers are encouraged to support the non-profit medical education effort by liking and subscribing to the channel.

Takeaways

• 🧠 There are four main types of stroke: acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and venous sinus thrombosis.
• 🩸 Acute ischemic stroke can be caused by a blood clot traveling to the brain or dislodgement of an atherosclerotic plaque.
• 🚫 Chronic hypertension can lead to the formation of microaneurysms, causing intracerebral hemorrhage.
• 🧬 Amyloid deposits and tumors can cause blood vessel rupture and bleeding within the brain parenchyma.
• 🤕 Traumatic head injuries can lead to both intracerebral hemorrhage and subarachnoid hemorrhage by damaging blood vessels.
• 🩹 Venous sinus thrombosis is often caused by a hypercoagulable state due to various factors like genetic predisposition or use of birth control pills.
• 🔍 The pathogenesis of ischemic stroke includes small artery occlusion, large artery atherosclerosis, and cardioaortic embolism.
• 🧬 Reduced cerebral blood flow from any cause of ischemic stroke leads to a cascade of events including anaerobic metabolism, brain edema, and inflammation.
• 💊 Excitotoxicity from increased glutamate levels contributes to neuronal damage and inflammation in ischemic stroke.
• 🔄 The accumulation of lactate and the release of cytokines from damaged astrocytes and microglia further contribute to brain inflammation.
• 📉 Ischemic stroke results in characteristic symptoms like weakness, slurred speech, visual field losses, and autonomic dysfunction due to the complex interplay of necrosis and inflammation.

Q & A

What are the four main types of stroke mentioned in the video?

The four main types of stroke mentioned are acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and venous sinus thrombosis.

What are the two main pathophysiological causes of acute ischemic stroke?

The two main causes are a blood clot formed in the left side of the heart traveling to the brain and the dislodgement of an atherosclerotic plaque formed in the internal carotid arteries traveling to the brain.

How does chronic hypertension contribute to stroke?

Chronic hypertension can cause microaneurysms to form in the small arteries of the brain, leading to hypertensive hemorrhage and potentially resulting in intracerebral hemorrhage.

What is the role of amyloid deposits in the context of stroke?

Amyloid deposits can cause vascular fragility, leading to the rupture of blood vessels within the brain and resulting in bleeding within the brain parenchyma.

What are the three common causes of subarachnoid hemorrhage?

The three common causes are arterial venous malformation, traumatic head injury leading to a cerebral contusion that damages blood vessels in the subarachnoid space, and a ruptured arterial aneurysm.

How does venous sinus thrombosis typically occur?

Venous sinus thrombosis usually occurs due to a hypercoagulable state caused by hereditary or familial causes, exogenous estrogen such as birth control pills, or pregnancy and postpartum situations.

What is the impact of reduced cerebral blood flow on brain tissue during an ischemic stroke?

Reduced cerebral blood flow leads to a reduction of oxygen and glucose provided to the brain tissue, resulting in increased anaerobic metabolism, which is inefficient and reduces the amount of ATP available to neurons.

How does the lack of ATP affect the function of neurons during an ischemic stroke?

The lack of ATP reduces the function of sodium-potassium pumps on the surface of neurons, leading to sodium accumulation in the interstitial tissues of the brain and water movement by osmosis, causing brain edema.

What is excitotoxicity and how does it contribute to brain damage during a stroke?

Excitotoxicity is a condition where an increased amount of glutamate, a neurotransmitter, contributes to neuronal damage. This results in increased calcium influx into neurons, activating catabolic enzymes and contributing to oxidative and nitrosative injury, leading to necrosis of brain tissue.

What is the significance of the blood-brain barrier breakdown during a stroke?

The breakdown of the blood-brain barrier during a stroke leads to inflammation in the brain, known as secondary inflammation, and allows for the infiltration of immune cells and proteins that can exacerbate brain damage.

How does the accumulation of lactate contribute to brain damage following a stroke?

The accumulation of lactate, a byproduct of increased anaerobic metabolism, is dangerous to brain tissue, leading to astrocyte death and the release of cytokines like TNF-alpha into the cerebral fluid, contributing to inflammation in the affected area.

Outlines

00:00

🧠 Overview of Stroke Types and Pathogenesis

This segment of the Calgary Guide video series introduces the topic of stroke, emphasizing the four main types: acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and venous sinus thrombosis. The narrator outlines the different pathogeneses for each type, focusing initially on acute ischemic stroke. Two primary causes for this type are discussed: blood clots originating from the left side of the heart and atherosclerotic plaques from the internal carotid arteries. The video promises a detailed slide presentation on the pathogenesis of acute ischemic stroke later and encourages viewers to support the educational content by liking and subscribing.

05:01

🩸 Detailed Pathogenesis of Acute Ischemic Stroke

The second paragraph delves into the detailed pathogenesis of acute ischemic stroke. It explains how reduced cerebral blood flow due to various causes, such as small artery occlusion, large artery atherosclerosis, and cardioaortic embolism, leads to a cascade of events. These include decreased ATP production, impaired sodium-potassium pump function, increased interstitial sodium and water, brain edema, blood-brain barrier breakdown, and inflammation. The paragraph also covers the role of glutamate in excitotoxicity, the release of catabolic enzymes and cytokines leading to necrosis, and the impact of lactate accumulation. The summary concludes by linking these physiological changes to the clinical symptoms of ischemic stroke, such as weakness, slurred speech, and visual field losses.

Keywords

💡Stroke

A stroke is a medical condition in which the blood supply to a part of the brain is interrupted or reduced, leading to brain tissue damage. In the video, stroke is the central theme, with a focus on its different types and their respective pathogeneses. The script discusses four main types of stroke, highlighting their impact on brain function and the associated symptoms.

💡Pathogenesis

Pathogenesis refers to the cellular and physiological processes that lead to the development and progression of a disease. In the context of the video, pathogenesis is used to describe the mechanisms by which different types of strokes occur, such as through blood clots, atherosclerotic plaques, or hypercoagulable states.

💡Acute Ischemic Stroke

Acute ischemic stroke is a type of stroke caused by a sudden blockage of a blood vessel supplying the brain, leading to a lack of oxygen and nutrients to brain cells. The video script mentions this as one of the main types of stroke and dedicates a slide to discussing its pathogenesis in more detail, emphasizing the importance of understanding its causes.

💡Intracerebral Hemorrhage

Intracerebral hemorrhage is a type of stroke where a blood vessel within the brain ruptures, causing bleeding into the brain tissue. The script explains that this can be caused by various factors such as chronic hypertension, amyloid deposits, or brain tumors, and is one of the intracranial hemorrhages discussed.

💡Subarachnoid Hemorrhage

Subarachnoid hemorrhage is a type of stroke resulting from bleeding in the subarachnoid space, the area between the brain and the thin tissues that cover the brain. The video script identifies arterial venous malformations, traumatic head injuries, and ruptured arterial aneurysms as common causes.

💡Venous Sinus Thrombosis

Venous sinus thrombosis is a rare type of stroke caused by a blood clot in the dural venous sinuses, which are the blood vessels that drain blood from the brain. The script mentions that this condition is often caused by a hypercoagulable state, which can be due to hereditary factors, exogenous estrogen, or pregnancy.

💡Atherosclerosis

Atherosclerosis is a condition where plaque builds up inside the arteries, which can restrict blood flow and lead to various cardiovascular diseases, including stroke. In the video, atherosclerosis is noted as a cause of acute ischemic stroke due to the dislodgement of plaques from the internal carotid arteries.

💡Microaneurysms

Microaneurysms are small, weak spots in the blood vessel walls that can bulge and leak blood. The script explains that chronic hypertension can lead to the formation of microaneurysms in the brain's small arteries, which can result in intracerebral hemorrhage.

💡Aneurysm

An aneurysm is a bulging, weakened area in the wall of a blood vessel that can rupture, leading to bleeding. The video script identifies a ruptured arterial aneurysm as a common cause of subarachnoid hemorrhage, which is a serious and often life-threatening type of stroke.

💡Hypercoagulable State

A hypercoagulable state is a condition where the blood is more likely to clot than in a healthy individual. The video script discusses how this state, which can be due to hereditary or acquired factors, can lead to venous sinus thrombosis, one of the types of stroke.

💡Excitotoxicity

Excitotoxicity refers to the pathological process by which neurons are damaged and killed by excessive stimulation by neurotransmitters such as glutamate. In the context of the video, excitotoxicity is mentioned as a result of increased glutamate levels in the brain following a stroke, contributing to neuronal damage.

Highlights

There are four main types of stroke: acute ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and venous sinus thrombosis.

Acute ischemic stroke can arise from a blood clot or dislodgement of an atherosclerotic plaque.

Atherosclerosis in the brain can lead to blood clot formation within the blood vessels.

Chronic hypertension can cause microaneurysms leading to intracerebral hemorrhage.

Amyloid deposits causing vascular fragility can result in bleeding within the brain parenchyma.

Brain tumors and traumatic head injuries can lead to intracerebral hemorrhage.

Arterial venous malformations can spontaneously bleed within the brain parenchyma.

Inherited and acquired coagulopathies can cause bleeding within the brain parenchyma.

Subarachnoid hemorrhage is caused by the rupture of an artery in the subarachnoid space.

Arterial venous malformation and traumatic head injury are common causes of subarachnoid hemorrhage.

Ruptured arterial aneurysm is a typical cause of subarachnoid hemorrhage.

Venous sinus thrombosis is usually caused by a hypercoagulable state.

Conditions like birth control pills, pregnancy, and postpartum situations can lead to venous sinus thrombosis.

All types of stroke impair blood supply to the brain, resulting in loss of function and characteristic symptoms.

Acute ischemic stroke can be caused by small artery occlusion, large artery atherosclerosis, and cardioaortic embolism.

Reduced cerebral blood flow leads to reduced oxygen and glucose supply, causing anaerobic metabolism.

Anaerobic metabolism results in reduced ATP production, affecting sodium-potassium pump function.

Increased brain interstitial edema leads to compression of blood vessels and brain tissue.

Excitotoxicity due to increased glutamate levels contributes to neuronal damage.

The accumulation of lactate due to anaerobic metabolism is dangerous to brain tissue.

The pathogenesis of ischemic stroke involves a complex interplay of necrosis, inflammation, and increasing infarct volume.

Transcripts

welcome back to the calgary guide video

series today we're going to be talking

about stroke and its pathogenesis

note that there are four main types of

stroke and that i will also be

presenting a slide on the pathogenesis

of acute ischemic stroke later on in

this video so stay tuned for that but

first please consider supporting us in

this non-profit work to improve medical

education by liking this video just as

it's starting out and by subscribing to

my channel

thanks

and with that let's get started

as i said already there are four main

types of stroke there's acute ischemic

stroke intracerebral hemorrhage

subarachnoid hemorrhage and venous sinus

thrombosis

each of these different types of stroke

have their own different pathogenesis

for acute ischemia this type of stroke

has two main pathophysiological causes

first ischemic stroke can arise from a

blood clot commonly formed in the left

side of the heart traveling to the brain

the other cause is the dislodgement of

an atherosclerotic plaque

formed in the internal carotid arteries

traveling to the brain

of course atherosclerosis can also

happen in the brain leading to blood

clot formation within the blood vessels

of the brain

the occlusion of cerebral blood vessels

is what causes acute ischemic stroke

again stay tuned for the latter half of

this video where i'll be talking about

the pathogenesis of acute ischemic

stroke in more detail

in terms of the two different types of

intracranial hemorrhages intracerebral

hemorrhage and a subarachnoid hemorrhage

they share a common group of various

causes

first

chronic hypertension can cause

microaneurysms to form in the small

arteries of the brain and hypertensive

hemorrhage in this manner often leads to

bleeding within the brain parenchyma

leading to intracerebral hemorrhage

amyloid deposits causing vascular

fragility can also cause the rupture of

blood vessels within the brain resulting

in bleeding within the brain parenchyma

there can also be tumors in the brain

that hemorrhage leading to intracerebral

hemorrhage traumatic head injuries can

cause coup or contra coupe forces that

damage blood vessels within white matter

leading to bleeding within the brain

parenchyma

arterial venous malformations can

spontaneously bleed within the brain

parenchyma in addition issues outside

the brain such as inherited and acquired

coagulopathies can cause bleeding

anywhere within the body and if it

occurs within the brain parenchyma that

will also lead to an intracerebral

hemorrhage

in terms of the causes of a subarachnoid

hemorrhage which is the rupture of an

artery in the subarachnoid space

three common causes of that include

an arterial venous malformation

traumatic head injury leading to a

cerebral contusion that damages blood

vessels in the subarachnoid space

as well as a ruptured arterial aneurysm

usually in the anterior circulation of

the brain

finally the fourth type of stroke venous

sinus thrombosis is usually caused by a

hypercoagulable state either due to

hereditary or familial causes exogenous

estrogen such as birth control pills

pregnancy and postpartum situations

these situations result in a

hypercoagulable state one of the three

prongs of virtual's triad which leads to

thrombosis occurring in the large venous

sinuses of the brain which then go on to

obstruct venous drainage and cause the

signs and symptoms that they do

all four of these types of stroke impair

blood supply to the affected area of the

brain resulting in the loss of function

and associated symptoms that are

characteristic of each type of stroke

and that's it for the pathogenesis of

stroke as a general topic next we move

on to discussing the pathogenesis of

acute ischemic stroke in more detail

this is the carrier guide slide on the

pathogenesis of ischemic stroke one of

the four main causes of stroke

ischemic stroke can be caused by a

variety of issues

first small artery occlusion which is

defined as acute infarction of basal or

brain stem penetrating arteries that are

less than 20 millimeters in diameter

second cause of exceeding stroke is

large artery atherosclerosis which is

defined as an atherosclerotic plaque

reducing the diameter of intra or extra

cranial blood vessels by over 50 percent

the third cause of xemic stroke is

cardioaortic embolism which is defined

as a blood clot that first forms in the

heart for example because of atrial

fibrillation then traveling to the brain

via the vasculature there are also other

and unknown causes of ischemic stroke

note that the pathogenesis of xemic

stroke is not exact and not very well

known however we do know that each one

of these causes will lead to the

reduction of cerebral blood flow or cbf

reduced cerebral blood flow will reduce

oxygen and glucose provided to the

tissue of the brain in the location of

the infarct that results in an increased

amount of anaerobic metabolism anaerobic

metabolism is an inefficient process

which reduces the amount of atp

adenosine triphosphate available to the

neurons atp is responsible for the

function of sodium potassium pumps on

the surface of neurons so less atp will

reduce their function reduced function

of sodium potassium pumps will result in

sodium accumulating in the interstitial

tissues of the brain outside neurons and

as a result water will move to the

interstitial regions of the brain

outside neurons by osmosis the increased

presence of water in the interstitial

tissues of the brain will cause brain

edema which will compress the blood

vessels in the brain as well as brain

tissue itself

increased brain interstitial edema will

also lead to the breakdown of the

blood-brain barrier all of which combine

to cause inflammation in the brain note

that this is a type of inflammation

known as secondary inflammation we'll

talk about primary inflammation in just

a bit dysfunction of sodium potassium

pumps on neurons can also result in

increased sodium and calcium influx into

the neuron as well as potassium outflux

that will result in depolarization of

the neuron and the neurons releasing

glutamate a neurotransmitter reduced atp

can also directly cause astrocytes in

the brain to release glutamate a

neurotransmitter and so the increased

amount of glutamate in the brain

contributes to an overall level of

excitotoxicity for the brain this

results in increased calcium influx into

neurons which activates catabolic

proteases lipases and nucleases as well

as contributes to oxidative and

nitrosative injury leading to necrosis

of brain tissue

increased anaerobic metabolism also

leads to the increased production of

lactate as a byproduct the accumulation

of lactate is dangerous to brain tissue

leading to astrocyte death releasing

cytokines like tnf-alpha into the

cerebral fluid contributing to

inflammation of the brain in that area

the clearance of debris by microglia

will also release cytokines into that

area of the brain contributing to

inflammation

reduced cerebral blood flow will also

increase glucose metabolism in the

penumbra which is the section of the

brain that's surrounding the acute

infarct that will lead to peri-infarct

depression-like depolarizations which

activates biochemical pathways that

increase the volume of the infarct in

other words increasing the amount of

brain tissue that continues to die from

the stroke and so this combination of

necrosis

inflammation and the negative spiral

that contributes to increasing the

volume of the infarct all add up to

cause the weakness slurred speech visual

field losses and autonomic dysfunction

that are characteristic of ischemic

stroke

and there you have it two slides to

summarize the pathogenesis of stroke

both stroke in general and ischemic

stroke

if you found these two series of

character guide slides useful please

like this video and subscribe to our

channel

for more concise summaries about disease

pathophysiology thank you for your

support and see you in the next video