Cerebrovascular Disease Pathology PDF

Pathology of Cerebrovascular Disease Prof. Dr. Süheyla Uyar Bozkurt Marmara University School of Medicine 2023-2024  cerebrovascular disease(CVD) injury to the brain as a consequence of altered blood flow grouped into ischemic and hemorrhagic etiologies,...

Pathology of Cerebrovascular Disease Prof. Dr. Süheyla Uyar Bozkurt Marmara University School of Medicine 2023-2024  cerebrovascular disease(CVD) injury to the brain as a consequence of altered blood flow grouped into ischemic and hemorrhagic etiologies, with tissue infarction the ultimate consequence of both.  cerebrovascular disease(CVD) 3rd leading cause of death «stroke»clinical designation applies to all condition  stroke Definition neurologic signs and symptoms that can be explained by a vascular mechanism, have an acute onset, and persist beyond 24 hours. (If symptoms disappear within 24 hours, the event is termed “transient ischemic event.”)  cerebrovascular disease(CVD) as two processes: 1)Hypoxia, ischemia, and infarction resulting from impairment of blood supply and oxygenation of CNS tissue embolism thrombosis 2)Hemorrhage resulting from rupture of CNS vessels (hypertension and vascular anomalies) Hypoxia/ischemia normally; The brain requires a constant supply of glucose and oxygen Although the brain accounts for only 1% to 2% of body weight, it receives 15% of the resting cardiac output and accounts for 20% of the total body oxygen consumption.  So brain needs oxygen brain is strictly dependent on aerobic metabolism to meet its constant energy demands, it may be deprived of oxygen by either hypoxemia (low blood oxygen content) or ischemia (inadequate blood flow)  Factors effecting survival When blood flow to a portion of the brain is reduced, the survival of the tissue at risk depends on; the presence of collateral circulation the duration of ischemia the magnitude and rapidity of the reduction of flow.  acute ischemic injury Global cerebral Focal cerebral ischemia; ischemia (ischemic/hypoxic follows reduction or cessation of blood flow to a localized area of encephalopathy) the brain due to large-vessel when there is a disease (such as embolic or generalized reduction of thrombotic arterial occlusion,) cerebral perfusion, as in or to small-vessel disease cardiac arrest, shock, and (vasculitis). severe hypotension  FOCAL CEREBRAL ISCHEMIA Cerebral arterial occlusion may lead to focal ischemia to infarction of a specific region within the territory of distribution of the damaged vessel. size, location Depend on adequacy shape of the infarct of collateral flow extent of tissue damage  collateral circulation The major source of collateral flow is the circle of Willis (supplemented by the external carotid-ophthalmic pathway). Partial and inconstant reinforcement is available over the surface of the brain for the distal branches of the anterior, middle, and posterior cerebral arteries through cortical- leptomeningeal anastomoses  In contrast, there is no collateral flow for the deep penetrating vessels supplying structures such as the thalamus, basal ganglia, and deep white matter Infarction from Obstruction of Local Blood Supply (Focal Cerebral Ischemia) Occlusive vascular disease that cause cerebral infaction; thrombosis embolism vasculitis  Thrombotic occlusion of the cerebral arteries is most commonly caused by acute change of vulnerable atherosclerotic plaques carotid bifurcation most common sites of primary origin of the middle cerebral artery thrombosis either end of the basilar artery..  Basic structure of an atherosclerotic plaque. Atherosclerosis is an intimal-based process with a complex interplay of cells and extracellular materials. atherosclerosis  thrombosis Rupture, ulceration, or erosion of the surface of atheromatous plaques exposes the blood stream to highly thrombogenic substances and leads to thrombosis, which can partially or completely occlude the vessel lumen Atherosclerotic plaque rupture. A) Plaque rupture without superimposed thrombus in a patient who died suddenly. (B) Acute coronary thrombosis superimposed on an atherosclerotic plaque with focal disruption of the fibrous cap, Atherosclerosis-trombosis  Thrombi cause progressive narrowing of the lumen, anterograde extension, may progress to fragmentation and distal embolization.  embolism Something that travels through the Origins of the emboli; bloodstream, lodges in a blood vessel Cardiac mural thrombi -the and blocks it. most common MI, valvular dis.,atrial fibrillation Thromboemboli arising in arteries, mostly originating over atheromatous plaques within the carotid arteries. Emboli associated with cardiac surgery Emboli of other material (tumor, fat, or air).  embolism The territory of distribution of the middle cerebral artery- is most frequently affected by embolic infarction the incidence is about equal in the two hemispheres. Emboli tend to lodge branching of blood vessel or in areas of preexisting luminal stenosis.  vasculitis İnfectious vasculitis – Tbc, syphilis, cmv, – Aspergillus Non-infectious vasculitis PAN primary angiitis of CNS  Focal cerebral infarcts Based on the on the presence of secondary hemorrhage Hemorrhagic-red Non-hemorrhagic-pale Multiple-confluent Bland-anemic Petechial hemorrhage Embolic events Usually ass with thrombosis Bleeding is secondary to reperfusion of damaged vessel Occlusive infarcts generally start as nonhemorrhagic  Convertion of a bland infarct into a hemorrhagic one secondary hemorrhagic transformation Secondary hemorrhage can occur from ischemia- reperfusion injury following spontaneous or therapeutic dissolution or fragmentation of the intravascular occlusive material. develops if the causative ischemic event lasts long enough to damage small blood vessels in the affected area; the resulting reperfusion hemorrhages are largely petechial in nature, but may be multiple or even confluent Hemorrhagic Bland infact infarct hemorrhagic infarct with punctate hemorrhages, consistent with ischemia- reperfusion injury, is present in the temporal lobe.  Clinical management The clinical management of patients with nonhemorrhagic and hemorrhagic infarcts differs greatly. (thrombolytic therapy is contraindicated in a patient with brain hemorrhage of any etiology )  nonhemorrhagic (pale)infarct gross morphology During the first 6 hours of irreversible injury; little 48 hours; the tissue becomes pale, soft, and swollen corticomedullary junction becomes indistinct. 2 to 10 days; the brain becomes gelatinous and friable, 10 days to 3 weeks, the tissue liquefies, eventually leaving a fluid-filled cavity that continues to expand until all of the dead tissue has been removed  Acute infarct-microscopically After the first 6 to 12 hours; Neuronal necrosis (increased eosinophilia of the cytoplasm followed by nuclear pyknosis and karyorrhexis; “dead red neurons”); both cytotoxic and vasogenic edema are present. Loss of the usual tinctorial characteristics of white- and gray-matter structures. Endothelial and glial cells,swell, and myelinated fibers begin to disintegrate. Up to 48 hours, neutrophilic emigration progressively increases and then falls off Acute ischemic injury causes diffuse eosinophilia of neurons, which are beginning to shrink.  subacute (evolving) infarct- microscopically Phagocytic cells, are evident at 48 to 72 hours and become the predominant cell type in the ensuing 2 to 3 weeks. The macrophages become filled with the products of myelin breakdown or blood and may persist in the lesion for months to years.  subacute (evolving) infarct microscopically Reactive astrocytes and newly formed vessels can be seen at the periphery of the lesion as early as 1 week after the insult. As the process of liquefaction and phagocytosis proceeds, astrocytes at the edges of the lesion progressively enlarge, divide, and develop a prominent network of cytoplasmic extensions.  Subacute infact After about 10 days, the lesion is characterized by the presence of foamy macrophages and adjacent reactive gliosis with neovascularization  Healed infarct After several months, astrocytic response precedes, leaving behind a dense meshwork of glial fibers admixed with new capillaries and some perivascular connective tissue. Remote small infarct is seen as an area of tissue loss surrounded by residual gliosis.  the cavitary portions (*) surrounded by reactive > 3 mos.after the ischemic infarct astrocytic zones (glial scars) (blue bands). Old cystic infarct showing cavitation from loss of brain parenchyma.  hemorrhagic infarctions parallel ischemic infarctions, with the addition of blood extravasation and resorption. inflammatory cells and red blood cells in the damaged vessel that has been reperfused after an interval of ischemia.  Lacunar infarct Hypertension affects the deep penetrating arteries supplying the basal ganglia and hemispheric white matter as well as the brainstem. These cerebral vessels develop arteriolar sclerosis and may become occluded; If this disease progresses to thrombosis and complete vessel occlusion, the end-result is development of small cavitary infarcts known as lacunes or lacunar infarcts  Lacunar infarct Single-multiple Small Cavitary infarcts-lacunae Lake like areas 2 weeks after the "glial scar" Laminar (pseudolaminar) necrosis In the cerebral neocortex, the neuronal loss and gliosis are uneven, with preservation of some layers and destruction of others, producing a pattern of injury termed laminar necrosis.  Cerebrovascular disease(CVD) as two processes: 1)Hypoxia, ischemia, and infarction resulting from impairment of blood supply and oxygenation of CNS tissue embolism thrombosis 2)Hemorrhage resulting from rupture of CNS vessels (hypertension and vascular anomalies)  INTRACRANIAL HEMORRHAGE Hemorrhages may occur at any site within the CNS. Secondary hemorrhages; in infarcts caused by only partial or transient vascular obstruction. Primary hemorrhages; Epidural or subdural space; related to trauma Brain parenchyma: underlying cerebrovascular disease  intracerebral(intraparanchymal) hemorrhage Rupture of a small intraparenchymal vessel can result in a primary hemorrhage within the brain, often associated with sudden onset of neurologic symptoms (stroke); should not be confused with the secondary hemorrhagic transformation of an occlusive infarct  intracerebral(intraparanchymal) hemorrhage most commonly in middle to late adult life, with a peak incidence at about 60 years of age  İntracerebral(intraparanchymal) hemorrhage ganglionic hemorrhages; When the hemorrhages occur in the basal ganglia and thalamus, lobar hemorrhages:in the lobes of the cerebral hemispheres Other  Hypertensive hemorrhage is the most common underlying cause of primary brain parenchymal hemorrhage, more than 50% of clinically significant hemorrhages  Hypertension causes a number of abnormalities in vessel walls, accelerated atherosclerosis in larger arteries hyaline arteriolosclerosis in smaller vessels proliferative changes frank necrosis of arterioles Minute aneurysm-Charcot Bouchard aneurysm esp in basal gagnglia Hyaline arteriosclerosis  Hypertensive intraparenchymal hemorrhage originate in the putamen (50% to 60%) thalamus, pons, cerebellar hemispheres (rarely) other (A)Massive hypertensive ganglionic hemorrhage rupturing into a lateral ventricle. (B) Hyaline arteriolosclerosis (fibrosis and thickening of the arteriolar walls) develops in the basal ganglia and subcortical white matter of patients with long-standing hypertension; Hypertensive hemorrhage Hypertensive hemorrhage  Cerebral amyloid angiopathy (CAA) CAA is a condition in which amyloidogenic peptides, (Aβ40) nearly always the same one found in Alzheimer disease deposit in the walls of medium- and small- caliber meningeal and cortical vessels. Amyloid deposition can weaken the vessel wall and lead to hemorrhage; numerous small hemorrhages within the brain (“microbleeds”). Cerebral amyloid angiopathy (CAA)  Cerebral amyloid angiopathy (CAA) The underlying vascular abnormality is typically restricted to the leptomeningeal and cerebral cortical vessels.  amyloid angiopathy (CAA) dense and uniform deposits of amyloid  Morphology of intraparenchymal hemorrhages characterized by a central core of clotted blood that compresses the adjacent parenchyma; leads to secondary infarction of the affected brain tissue, with anoxic neuronal and glial changes as well as edema. hemosiderin- and lipid-laden macrophages appear, proliferation of reactive astrocytes is seen at the periphery of the lesion;  Subarachnoid Hemorrhage most frequent causes; rupture of a saccular (berry) aneurysm. extension of a traumatic hematoma rupture of a hypertensive intracerebral hemorrhage into the ventricular system, vascular malformation hematologic disturbances tumors  aneurysm Saccular is the most common type of intracranial aneurysm. Other aneurysm types; atherosclerotic (fusiform; mostly of the basilar artery), mycotic, traumatic dissecting.  Saccular aneurysm most often found in the anterior circulation, %90  saccular aneurysms the etiology of is unknown. genetic factors structural abnormality of the involved vessel (absence of smooth muscle and intimal elastic lamina) suggests that they are developmental anomalies. Risc factors: smoking and hypertension Morphology of saccular aneurysm. is a thin-walled outpouching usually at an arterial branch point along the circle of Willis a few mm to 2 or 3 cm in diameter bright red, shiny surface a thin, translucent wall.  Morphology of saccular aneurysm The sac is made up of thickened hyalinized intima. The adventitia covering the sac is continuous with that of the parent artery. No muscular wall No intimal elastic lamina Atheromatous plaques, calcification, or thrombi may be found in the wall or lumen of the aneurysm. No muscular wall 1- endothelium No intimal elastic lamina 2-thickened hyalinized intima. 3-The adventitia covering the sac is continuous with that of the parent artery Morphology of saccular aneurysm Brownish discoloration of the adjacent brain and meninges is evidence of prior hemorrhage. Rupture usually occurs at the apex of the sac with extravasation of blood into the subarachnoid space, brain, or both.  Mycotic aneurysm is an infection of vessel wall which can be bacterial, fungal, or viral in origin; they are a rare but severe complication of systemic infection and atherosclerosis  Vascular Malformations classified into 4 groups: arteriovenous malformations İncrease risc of cavernous malformations hemorrhage capillary telangiectasias venous angiomas. 1-Arteriovenous malformations (AVM) involve vessels in the subarachnoid space or within the brain. tangled network of wormlike vascular channels has prominent, pulsatile arteriovenous shunting with high blood flow. They are composed of greatly enlarged blood vessels separated by gliotic tissue, often with evidence of prior hemorrhage. 1-Arteriovenous malformations (AVM) 1-Arteriovenous malformations (AVM) Large arteriovenous malformation in the left cerebral hemisphere.  2-cavernous malformations consist of greatly distended, loosely organized vascular channels with thin, collagenized walls and are devoid of intervening nervous tissue Mostly occur in the cerebellum, pons, and subcortical regions.  2-cavernous malformations Foci of old hemorrhage, infarction, and calcification frequently surround the abnormal vessels. 3-Capillary telangiectasias are microscopic foci of dilated, thin-walled vascular channels separated by relatively normal brain parenchyma most frequently in the pons. 4-Venous angiomas (varices) consist of aggregates of ectatic venous channels.