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The initial injury mechanism in ICH is compressing brain parenchyma by hematoma’s mass

effect, resulting in physical disruption of parenchymal architecture.27 Increased intracranial


pressure due to expansion of hematoma can affect blood flow, mechanical deformation,
neurotransmitter release, mitochondrial dysfunction and membrane depolarization. As a result,
neuronal injury in perihematomal area contains the edema and inflammatory environment by
blood-derived factors.28–30 A secondary mechanism of brain injury is related to clotting
cascade, in particular thrombin, after endothelial damage and hemoglobin breakdown.31–33
Thrombin causes inflammatory cells to infiltrate the brain, proliferation of mesenchymal cells,
formation of brain edema and scar tissue.34 Thrombin binds to protease-activated receptors 1
and activates the central nervous system microglia and complement cascade. As a result,
multiple immune pathways are activated, which contributes to apoptosis and necrosis. Heme
influx in neuron after endothelial damage leads to iron release and neuronal insult

Mekanisme awal dari injuri pada ICH adalah dengan menekan parenkim otak melalui hematoma
mass effect, menyebabkan gangguan fisik dari arsitektur parenkim otak. Peningkatan tekanan
intracranial akibat ekspansi dari hematoma dapat mempengaruhi aliran darah, deformasi
mekanik, pelepasan neurotransmitter, disfungsi mitokondria dan depolarisasi membrane. Sebagai
hasilnya, injuri neuron pada daerah perihematom. Mekanisme kedua adalah berhubungan dengan
kaskade pembekuan darah, terutama thrombin, setelah terjadi kerusakan endotel dan pemecahan
hemoglobin. Thrombin menyebabkan sel-sel inflamasi menginfiltrasi jaringan parenkim otak,
proliferasi dari sel-sel mesenkim, pembentukan edema otak dan jaringan parut. Thrombin terikat
pada protease-activated receptor 1 dan mengaktivasi microglia dan kaskade komplemen. Sebagai
hasilnya, berbagai macam jalur imun teraktivasi, yang berperan terhadap terjadinya apoptosis
dan nekrosis neuron otak.
Pathogenesis The hypertensive vascular lesion that leads to arterial rupture in some cases
appears to arise from an arterial wall altered by the effects of hypertension, i.e., the change
referred to in a preceding section as segmental lipohyalinosis and the false aneurysm
(microaneurysm) of Charcot-Bouchard. Ross Russell has affirmed the relationship of these
microaneurysms to hypertension and hypertensive hemorrhage and their frequent localization on
penetrating small arteries and arterioles of the basal ganglia, thalamus, pons, and subcortical
white matter. However, in the few hemorrhages examined in serial sections by our colleague C.
M. Fisher, the bleeding could not be traced to Charcot-Bouchard aneurysms. Takebayashi and
coworkers, in an electron microscopic study, found breaks in the elastic lamina at multiple sites,
almost always at bifurcations of the small vessels. Possibly these represent sites of secondary
rupture from tearing of small vessels by the expanding hematoma.

Hypertension affects the deep penetrating arteries and arterioles that supply the basal ganglia and
hemispheric white matter as well as the brain stem. Hypertension causes several changes,
including hyaline arteriolar sclerosis in arterioles. Arteriolar walls affected by hyaline change are
weaker than are normal vessels and are more vulnerable to rupture. In some instances, chronic
hypertension is associated with the development of minute aneurysms in vessels that are less
than 300 μm in diameter. These Charcot-Bouchard microaneurysms can rupture.

Patogenesis
Lesi vascular hipertensif yang berujung pada ruptur arteri pada beberapa kasus disebabkan oleh
perubahan dinding arteri yang disebabkan oleh hipertensi. Hipertensi menyebabkan beberapa
perubahan, termasuk hyaline arteriolar sclerosis pada arteriol. Perubahan hialin pada dinding
arteriolar menyebabkan dinding arteriol tersebut menjadi lebih lemah dibanding pembuluh darah
normal dan menjadi mudah rupture. Pada beberapa keadaan, hipertensi kronik berhubungan
dengan terjadinya anurisma pada pembuluh darah dengan diameter kurang dari 300 μm,
anurisma ini dikenal dengan nama Charcot-Bouchard microaneurysms, yang mudah rupture.
Anurisma tersebut dikelilingi oleh area perdarahan kecil dan dinding anurisma sering
menunjukkan perubahan berupa lipohyalinosis atau nekrosis fibrinoid. Proses ini ditandai dengan
destruksi dinding pembuluh darah dengan penimbunan material fibrinoid, ekspansi anurisma
fokal pada pembuluh darah yang terkena, oklusi trombotik, dan ekstravasasi dari sel darah
merah. Secara umum, perderahan serebri massif sering dihubungkan dengan rupturnya
mikroanurisma atau segmen lipohialinotik dari arteri kecil yang disebabkan oleh hipertensi
kronik.
Selain perubahan struktur dari dinding arteri serebral yang disebabkan oleh hipertensi kronik,
peningkatan tekanan darah secara akut diperkirakan memainkan peranan penting dalam
pathogenesis ICH. Meskipun kebanyakan pasien dengan ICH berhuungan dengan peningkatan
tekanan darah secara akut, banyak pasien yang tidak memiliki hipertensi dan tanda-tanda dari
hypertensive end-organ disease seperti hipertrofi ventrikel kiri, retinopati, atau nefropati.
Peningkatan tekanan darah secara cepat dapat menyebabkan ICH dengan segera, seperti pada
penyalahgunaan amfetamin atau kokain. Selain itu, peningkatan tekanan darah secara akut juga
dapat menjadi pencetus dari ICH spontan pada pasien dengan hipertensi kronik dengan anurisma
Charcot-Bouchard.
Angiopati amiloid merupakan salah satu penyebab terjadinya stroke hemoragik yg lebih sering
terjadi pada usia diatas 55 tahun. Hal ini sering tampak pada otak pasien dengan Alzheimer dan
berhubungan dengan perdarahan non-hipertensi pada lokasi lobar yang tidak biasa pada hemisfer
serebri. Penumpukan amiloid, yang secara kimiawi sama seperti plak Alzheimer, terlihat pada
tunika media dan adventitia dari arteri berukuran sedang dan kecil. Penumpukan material ini
menyebabka kelemahan pada dingding pembuluh darah dan meningkatkan risiko perdarahan.

3. Acute hypertension—In addition to structural changes in the cerebral arterial wall produced by
chronic hypertension, acute elevation of blood pressure appears to play a role in the pathogenesis
of intracerebral hemorrhage. Although most patients with intracerebral hemorrhage are
hypertensive following the event, many have no history of hypertension and lack such signs of
hypertensive end-organ disease as left ventricular hypertrophy, retinopathy, or nephropathy. It
has therefore been suggested that a sudden increase in blood pressure may itself be sufficient to
cause intracerebral hemorrhage, as with amphetamine or cocaine abuse. Acute elevation of blood
pressure may also be the immediate precipitating cause of intracerebral hemorrhage in
chronically hypertensive patients with Charcot-Bouchard aneurysms.

2. Chronic hypertension—Chronic hypertension appears to promote structural changes in the


walls of penetrating arteries, predisposing them to intracerebral hemorrhage. In 1888, Charcot
and Bouchard found minute aneurysms on the small intraparenchymal arteries of hypertensive
patients and postulated that aneurysmal rupture led to intracerebral hemorrhage. Subsequently,
Ross Russell showed microaneurysms of small resistance arteries in cerebral sites at which
hypertensive hemorrhages occur most commonly. Some aneurysms were surrounded by small
areas of hemorrhage, and the aneurysmal walls often showed changes of lipohyalinosis or
fibrinoid necrosis. These processes are characterized by destruction of the vessel wall with
deposition of fibrinoid material, focal aneurysmal expansion of the involved vessel, thrombotic
occlusion, and extravasation of red cells. There is now general agreement that massive cerebral
hemorrhage often follows the rupture of either a microaneurysmal or lipohyalinotic segment of a
small resistance artery and that the underlying lesion is caused by chronic hypertension.
Amyloid (congophilic) angiopathy is a pathologic diagnosis that is more frequently made in
people older than 55 years. This condition, which is unrelated to generalized amyloidosis and is
occasionally hereditary, commonly produces multiple, small hemorrhages. It often appears in the
brains of patients with Alzheimer's disease ( Chapter 425 ) and has been associated with
nonhypertensive hemorrhage in unusual lobar locations in the cerebral hemispheres. Amyloid
deposits, chemically similar to those in Alzheimer's plaques, are seen in the media and adventitia
of small and medium-sized arteries. Cerebral amyloid angiopathy (CAA) is a disease in which
amyloidogenic peptides-typically the same ones found in Alzheimer disease (see below)-deposit
in the walls of medium- and small-caliber meningeal and cortical vessels. This deposition results
in weakening of the vessel wall and increases the risk of hemorrhage. Since CAA is limited to
leptomeningeal and cortical vessels with sparing of the vasculature of white matter and deep gray
structures, hemorrhages associated with CAA have a distribution that is different from that of
hypertensive intraparenchymal hemorrhages. CAA-associated hemorrhages are often referred to
as lobar hemorrhages because of the involvement of the cerebral cortex.