Neuropathology 4 Flashcards
Cerebrovascular disease:
Includes all causes of vascular insult to the brain (wheather cerebral or not)
caused by hemorrhage or ischemia
What is ischemia?
restriction in blood supply
Major causes of cerebrovascular disease (stroke) include:
-Embolism
-Rupture of an atherosclerotic plaque
-Hypertension
-Rupture of a vessel (often an abnormal vessel)
Cerebrovascular disease can be broadly defined as three etiologic categories:
Focal ischemia: Most common
Hemorrhage: 2nd most common
Global/widespread ischemia due to hyperfusion: least common, most dependent on disease processes outside the brain
Global cerebral ischemia:
Severe hypotension usually results in syncope:
-consciousness resumes when blood pressure increases
-If blood pressure does not recover, then can result in global cerebral ischemia: If severe, results in brain death relatively quickly/ if less severe, some brain areas are less likely to be perfused than others (watershed areas/ most common is the border between anterior and middle cerebral artery territory-causes necrosis over anterior aspect of cortex just lateral to interhemispheric fissure)
Problem: not a local blockage, but global loss of blood flow to the majority of the brain
Blood flow and neuronal damage:
zero => death of brain tissue within 4-10min
< 16-18 mL/100g tissue/minute => infarction within an hour
< 20 mL/100g tissue/minute => ischemia without infarction
-Infarction will occur if poor perfusion remains for days
-this area is known as the penumbra (shadow)
-Cooling brain tissue (hypothermia) can be protective and extend neuronal viability/reduce ischemic damage
Cerebral ischemia:
Several special responses to ischemia in the central nervous system:
Necrosis in the very low/no-flow areas, apoptosis in the low-flow areas
Ischemic stroke progression:
Cerebral infarcts: Thrombotic:
The majority of thrombotic occlusions are due to atherosclerosis. Most common sites of primary thrombosis:
-carotid bifurcation
-Origin of the middle cerebral artery
-Either end of the basilar artery
Frequently associated with systemic diseases such as hypertension & diabetes
Thrombus:
A clot. (platelets, coagulation factors)
Atherosclerosis:
Deposition of plaque (LDL, cellular debris) within the wall of a large artery
if plaque ruptures => thrombosis
Other causes of local cerebral infarcts:
-Inflammation of blood vessels themselves (vasculitis, often autoimmune)
-Infectious vasculitis: immunosuppression and opportunistic infection (such as toxoplasmosis, aspergillosis, and CMV encephalitis)
-A clot forms in a site of abnormal blood flow:
1) abnormal blood flow or inadequate movement of blood, is sometimes known as stasis
2) blood stasis greatly increases the risk for clot formation => clot from one area of the body migrates to the brain
3) a vascular blockage that migrates and causes problems elsewhere is known as an embolus
Embolism:
Origins of emboli that can affect the brain arterial system:
- cardiac mural thrombi from myocardial infarcts, valvular disease, and atrial fibrillation (very common)
-Thromboemboli arising in arteries, most often originating over atheromatous plaques within the carotid arteries (very common)
-Fat from fractured bone, gas bubbles from decompression sickness
Primary thrombotic disease:
clot forms, obstructs blood flow to the brain at the site of clot formation.
Secondary thrombotic disease:
clot migrated from somewhere else = thromboembolism
Bone marrow embolus:
white matter hemorrhages that are fairly widely distributed
Lacunar infarcts:
Usually due to long term hypertension:
Small arteries and arterioles become narrowed with deposition of hyaline deposits around the walls (arteriosclerosis)
-this is a small artery disease, atherosclerosis is a large artery disease
Small infarcts occur (less than 15mm)
-could be clinically silent
-could have large repercussions
Areas at high risk: lenticular nucleus, thalamus, internal capsule, deep white matter, caudate nucleus, and pons
Hemorrhagic strokes:
Hemorrhages may occur at any site within the CNS:
-can occur post-infarct
-Epidural and subdural usually traumatic: subarachnoid is sometimes traumatic, but usually due to aneurysm rupture
Spontaneous intracerebral hemorrhage:
Usually rupture of a small vessel within the cerebral parenchyma in middle to late adulthood:
-hypertension seems to be the most common cause (50%)
-Cerebral hemorrhage responsible for death of 15% of hypertensives
Subarrachnoid hemorrhage (SAH):
Most SAH due to rupture of a saccular (berry) aneurysm.
Other causes:
-Extension of traumatic hematoma
-Rupture of a hypertensive intracerebral hemorrhage into the ventricular system
-Vascular malformation
-Hematologic disturbances
-Tumors
Pathogenesis-Saccular Aneurysms:
Etiology not fully understood:
most are sporadic, but some have a genetic basis:
-Autosomal-dominant polycystic kidney disease
-Ehlers-Danlos Syndrome, Marfan syndrome, arterial dysplasia, congenital causes of hypertension
-Neurofibromatosis type 1
Smoking and hypertension (present in 54%) predispose to their development.
Although they are sometimes referred to as congenital, they are not present at birth.
-develop over time due to “stress” on the vessel or vascular weakness
Stroke-treatment and diagnosis:
Early treatment of ischemic stroke can include “clot-busting” agents (if diagnosed within 4.5 hour window)
-no clot-busting for hemorrhagic strokes
hemorrhagic stroke-often surgery and/or blood-pressure lowering
Imaging modality of choice= CT scan
-lumbar puncture can help identify hemorrhage
Hypertensive encephalopathy:
Long-term hypertension can lead to thickening of small arteries, which increases the risk of:
-ischemia (lacunar infarcts)
-Intraparenchymal hemorrhage
Photo shows what a thickened arteriole wall looks like (circled)
The larger vessel beside it is a vein.
Thickening results from eosinophilic protein deposition and increased smooth muscle cells within the wall.
