Cerebrovascular Disease Pathology Flashcards
Cerebrovascular Disease
Any abnormality of the brain caused by a pathologic process of blood vessels.
Most prevalent neurologic disorder in terms of both morbidity and mortality.
Stroke
A vascular event in the nervous system, particularly when sx begin acutely.
Also called Cerebrovascular Accident (CVA)
Stroke
Epidemiology
3rd most common cause of death in the US
Male to Female 1.5:1
Peak age 60’s to 70’s
Cerebrovascular Disease
Pathogenesis
Two general pathologic processes:
- Thrombus or embolus ⇒ ↓ oxygenated blood to the brain ⇒ hypoxia and ischemia ⇒ infarction
- Leakage of blood into brain tissue ⇒ hemorrhage
- Can occur in isolation (blood vessel leaks due to HTN or aneurysm ruptures) or with infarction
- Some forms of hypertensive cerebrovascular disease combine aspects of both ⇒ can make treatment decisions difficult
Ischemic Encephalopathy
Brain is deprived of oxygen ⇒ loss of consciousness and may progress to permanent tissue damage
- Mechanism #1 ⇒ Reduction/loss of blood flow to the brain
- Ischemia, either transient or permanent, after interruption of the normal circulatory flow caused by:
- Reduction in perfusion pressure, as in hypotension
- Small or large-vessel obstruction by thrombus, plaque, embolus
- Mechanism #2 ⇒ Lack of oxygen to brain despite blood flow to brain
- Functional hypoxia in a setting of a low partial pressure of oxygen (pO2) caused by:
- Impaired oxygen-carrying capacity of the blood (ex. CO inhalation)
- Inhibition of oxygen use by tissue (ex. cyanide ingestion)
Cellular
Selective Vulnerability
- Varied susceptibility of neuronal populations in different regions of the CNS to ischemia
- Partly based on differences in regional cerebral blood flow and cellular metabolic requirements
- Neurons are the most sensitive cells
- Glial cells (oligodendrocytes and astrocytes) are also vulnerable
Regional
Selective Vulnerability
Patient with significant ischemic event may show a selective neurologic deficit afterward
Degrees of sensitivity to ischemia:
- Hippocampus ⇒ most sensitive structure
- Cerebellar Purkinje cells ⇒ 2nd most sensitive
- Neurons of the cerebral cortex ⇒ 3rd most sensitive
Ischemia ⇒ neuronal loss and gliosis ⇒ uneven destruction of the neocortex (preservation of some layers and involvement of others) ⇒ injury pattern termed laminar or pseudolaminar necrosis
Ischemia
Localization
Acute ischemic injury can be global or focal:
-
Global cerebral ischemia (ischemic/hypoxic encephalopathy)
- Seen with generalized reduction of cerebral perfusion ⇒ e.g. cardiac arrest, shock, and severe hypotension
-
Focal cerebral ischemia
- Follows reduction or cessation of blood flow to a localized area of the brain due to:
- Large-vessel disease (such as embolic or thrombotic arterial occlusion, often in the setting of atherosclerosis)
- Small-vessel disease (such as vasculitis or occlusion 2/2 arteriosclerotic lesions seen in HTN)
Border Zone (“Watershed”) Infarcts
-
Wedge-shaped areas of infarction in brain and spinal cord that lie at the most distal fields of arterial irrigation ⇒ area of increased vulnerability
- In cerebral hemispheres ⇒ border zone between ACA and MCA distributions at greatest risk
- Border zone infarcts are usually seen after hypotensive episodes
Ischemic Stroke
Classification
- Ischemic stroke mechanisms classified as embolic or thrombotic ⇒ embolic is more common
- Clinical classification based on the site of origin ⇒ large vessels, small vessels, heart, veins, etc.
- Large vessel thrombotic strokes subdivided into thrombo-occlusive (purely thrombotic) and thrombo-embolic (a piece of a thrombus detaches and moves to another site)
Embolic Infarction
- Most common mechanism for cerebral infarction
-
Sources of emboli include:
-
Thrombi
- Mural thrombi ⇒ due to MI or atrial fibrillation
- Thromboemboli ⇒ arises in arteries, most often from the internal carotid arteries
-
Emboli of other material
- Tumor, fat, air, vegetations from infective endocarditis
-
Thrombi
- Emboli tend to lodge where blood vessels branch or in areas of pre-existing luminal stenosis
- “Shower embolization,” as in fat embolism, may occur after fractures
- Causes generalized cerebral dysfunction with disturbances of higher cortical function and consciousness, often w/o localizing signs
- See widespread hemorrhagic lesions involving the white matter
Thrombotic Infarction
Thrombotic occlusion of vessels is the 2nd common mechanism for cerebral infarction
Thrombi ⇒ progressive narrowing of the lumen ± anterograde extension ⇒ ± fragmentation and distal embolization
-
Atherosclerosis ⇒ most common
- Most common sites: carotid bifurcation, origin of the MCA, and either end of the basilar artery
- Frequently associated w/ HTN and DM
- Vascular Inflammation ⇒ less common
Vascular Inflammation
Etiologies
Arteritis can be due to:
- Chronic meningitis with secondary changes to the vessels
- Temporal (Giant Cell) arteritis
- Infectious vasculitis (now mostly seen due to opportunistic infections)
- Polyarteritis Nodosa, Primary angiitis, Granulomatous angiitis
Hemorrhagic vs Non-Hemorrhagic
Infarction
Infarcts classified based on macroscopic and radiologic appearance:
-
Hemorrhagic (red) infarction
- Macroscopic ⇒ multiple, sometimes confluent, petechial hemorrhages
- Typically associated with embolic events
- Hemorrhage occurs 2/2 reperfusion of damaged vessels and tissue via collaterals or thrombolysis
-
Non-hemorrhagic (pale, bland, anemic) infarcts
- Usually associated with thrombosis
- Deciding whether/when to treat with anticoagulation is a complex process
Infarct
Pathologic Evolution
-
12-18 hours
- Microscopic ⇒ cytoplasmic eosinophilia
- Macroscopically ⇒ softening, lasts up to 24 hours
- 3 days ⇒ peak PMN response
-
7 days ⇒ peak monocyte/macrophage response
- MΦ filled with fat vacuoles due to myelin
- _Within 2-3 week_s ⇒ gliosis/astrocytosis (act like fibroblasts to fill in the void) and loss of tissue
- Eventually results in cystic cavity formation
Hypertensive
Cerebrovascular Disease
Diseases classified as a direct result of vessel rupture (hemorrhage) with HTN as a key risk factor:
Lacunar infarcts
Intraparenchymal and subarachnoid hemorrhage
Lacunar Infarcts
-
Infarcts caused by occlusion of small vessels
- Seen only in the nervous system
- Chronic untreated HTN ⇒ arteriolar sclerosis ⇒ occlusion of deep penetrating arteries and arterioles ⇒ single or multiple, small, cavitary infarcts called lacunes (lacunar infarcts)
- Supply the basal ganglia, hemispheric white matter, and brainstem
- Frequent locations: lenticular nucleus > thalamus > internal capsule > deep white matter > caudate nucleus > pons
- Microscopic appearance: cavities due to lost tissue with scattered fat-laden MΦ and surrounding gliosis
- Depending on location ⇒ clinically silent or causes severe neurologic impairment (can see a Parkinson’s-like syndrome)
Multi-Infarct Dementia
- Multiple, bilateral, gray matter (cortex, thalamus, basal ganglia) and white matter (centrum semiovale) infarcts over a period of time ⇒ vascular/multi-infarct dementia
- Characterized by dementia, gait abnormalities, and pseudobulbar signs, often with superimposed focal neurologic deficits
- Can see multifocal vascular disease in patients with:
- Cerebral atherosclerosis
- Vessel thrombosis or embolization from carotid vessels or from the heart
- Cerebral arteriolar sclerosis from chronic HTN
Intracranial Hemorrhage (ICH)
Overview
- Primary hemorrhage at any site within the head ⇒ can be in brain parenchyma or outside it
- Epidural and subdural hemorrhage usually due to trauma
-
Intraparenchymal hemorrhage often due to underlying cerebrovascular disease
- Results from damage to a vessel wall ⇒ dissects through brain and may secondarily destroy tissue
- Related to HTN
- Most frequent sites are the same as for lacunar infarction: basal ganglia, pons, cerebellum
- Can be large and acutely fatal due to mass effect
- If not fatal, blood is resorbed and tissue may not be badly damaged
Intracranial Hemorrhage (ICH)
Pathogenesis
- HTN causes:
- Accelerated atherosclerosis in larger arteries
- Hyaline arteriolosclerosis in smaller vessels
- Severe cases ⇒ proliferative changes and necrosis of arterioles
- Arteriolar walls affected by hyaline change are weaker than normal vessels ⇒ more vulnerable to rupture
-
Chronic HTN associated with development of minute aneurysms in small vessels, termed Charcot-Bouchard microaneurysms
- Can rupture and cause hemorrhage, most often in the basal ganglia
- Do not confuse with saccular aneurysms of larger intracranial vessels
Spontaneous Intraparenchymal Hemorrhages
- Usually occur in middle to late adult life
- Caused by rupture of a small intraparenchymal vessel
-
HTN is the most common underlying cause ⇒ ~50% of clinically significant primary brain parenchymal hemorrhages
- Conversely, brain hemorrhage accounts for ~ 15% of deaths among pts with chronic HTN
- Other local and systemic factors include:
- Cerebral Amyloid Angiopathy (CAA) – pt usually older, may have Alzheimer diagnosis
- Systemic coagulation disorders
- Open heart surgery
- Hemorrhage related to neoplasms
- Vasculitis, vascular malformations
-
HTN is the most common underlying cause ⇒ ~50% of clinically significant primary brain parenchymal hemorrhages
Acute Hypertensive Encephalopathy
- A severe, acute manifestation of HTN
- Hypertensive patient develops diffuse cerebral dysfunction ⇒ headaches, confusion, vomiting, and convulsions, ± coma
- Often does not remit spontaneously
- Need rapid intervention to ↓ accompanying ↑ ICP
- At autopsy:
- Gross: brain edema with petechiae
- Micro: fibrinoid necrosis of arterioles in the gray and white matter
- Intraparenchymal hemorrhage can also extend into the ventricles ⇒ intraventricular hemorrhage
Subarachnoid Hemorrhage
Hemorrhage into subarachnoid space of the meninges
Usually caused by bleeding from cerebral aneurysms
3 types to be discussed: Berry Aneurysms, Atherosclerotic Aneurysms, Mycotic Aneurysms
Berry Aneurysm
Overview
- Most common cause of subarachnoid hemorrhage
- Measures a few mm to 2 or 3 cm in diameter
- Have a bright red, shiny surface and a thin, translucent wall
- Often arise at the junctions of vessels due to defects in vessel walls at branch points
- Cerebral vessels only have one elastic lamina ⇒ especially prone to aneurysmal dilatation
Berry Aneurysm
Locations
-
Most occur in the anterior cerebral circulation
- Junction of the anterior cerebral and anterior communicating arteries
- Junction between the carotid arteries and the posterior communicating artery
- Trifurcation of the middle cerebral artery
- Can also occur in the posterior circulation, most often at the tip of the basilar artery
Atherosclerotic Aneurysms
Arise as dilatation of an entire part of an artery weakened by atherosclerosis.
Less common than berry aneurysms.
Mycotic Aneurysms
Arise as aneurysmal dilatations of vessel wall weakened by infectious disease, usually fungal.
Even less common.
Aneurysm Rupture
- Most benign outcome ⇒ minor bleeding into subarachnoid space
- Causes severe headache (‘worst I’ve ever had’) d/t meningeal irritation brought on by contact with blood
- Lumbar puncture would show lysed blood in the CSF ⇒ xanthochromia (yellow)
- Clinically evidence before rupture if aneurysm compresses a cranial nerve and causes effects such as pupillary dilation
- When aneurysm ruptures, resulting jet of blood can:
- Cause damage to the brain parenchyma in the area
- Be directed into the ventricle ⇒ blood clot formation ⇒ CSF obstruction ⇒ hydrocephalus
Arteriovenous Malformations (AVM)
- Largest intracerebral malformations
- Resemble a tangled network of wormlike vascular channels
- Have a prominent, pulsatile arteriovenous shunt with high blood flow through the malformation
- Tend to occur in cerebral hemispheres
-
Effects:
- Tissue destruction
- Secondary gliosis
- Bleeding, causing intraparenchymal or subarachnoid hemorrhage
Cavernous Hemangiomas
A benign tumor made up of blood vessels within the cavernous sinus.
Consist of greatly distended, loosely organized vascular channels with thin, collagenized walls.
Capillary Hemangiomas
Benign endothelial cell neoplasms.
Rarely cause sx during life.
