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2H. Pathology- CNS > Cerebrovascular Disease > Flashcards

Flashcards in Cerebrovascular Disease Deck (81)
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_______________ is the third leading cause of death (after heart disease and cancer) in
the United States; it is also the most prevalent neurologic disorder in terms of both morbidity
and mortality

Cerebrovascular disease


Cerebrovascular diseases include the expected three major categories,
________________ with patient management differing between groups.

  • thrombosis,
  • embolism,
  • and hemorrhage,


___________ is the clinical designation that applies to all these conditions, particularly when
symptoms begin acutely. 



From the standpoint of pathophysiology and pathologic anatomy, it is
convenient to consider cerebrovascular disease as two processes:

  1. • Hypoxia, ischemia, and infarction resulting from impairment of blood supply and oxygenation of CNS tissue
  2. • Hemorrhage resulting from rupture of CNS vessels


The most common cerebrovascular disorders are__________

  1.  global ischemia,
  2. embolism,
  3. hypertensive intraparenchymal hemorrhage,
  4. and ruptured aneurysm


The brain requires a constant supply of glucose and oxygen, which is delivered by the blood.
Although the brain accounts for only __________ of body weight, it receives______ of the resting
cardiac output and accounts for__________ of the total body oxygen consumption.

  1. 1% to 2%
  2.  15%
  3.  20%



The brain may be deprived of oxygen by
several mechanisms: 

  • hypoxia caused by a low partial pressure of oxygen (Po2),
  • impairment of the blood's oxygen-carrying capacity,
  • or inhibition of oxygen use in the tissue;
  • or ischemia, either transient or permanent, after interruption of the normal circulatory flow. Cessation of
  • blood flow can result from a reduction in perfusion pressure (as in hypotension), small- or largevessel
  • obstruction, or both.


When blood flow to a portion of the brain is reduced, the survival of the tissue at risk depends
on the________________

 These factors determine, in turn, the precise anatomic site and
size of the lesion and, consequently, the clinical deficit. 

 presence of collateral circulation, the duration of ischemia, and the magnitude and
rapidity of the reduction of flow.


Two principal types of acute ischemic
injury are recognized:

  1. Global cerebral ischemia 

2.  Focal cerebral ischemia


Global cerebral ischemia (ischemic/hypoxic encephalopathy) occurs when

 there is a
generalized reduction of cerebral perfusion, as in cardiac arrest, shock, and severe


Focal cerebral ischemia follows reduction or cessation of blood flow to a localized area
of the brain due to:

  1.  large-vessel disease (such as embolic or thrombotic arterial
  2. occlusion, often in a setting of atherosclerosis)
  3. or to small-vessel disease (such as vasculitis or occlusion secondary to arteriosclerotic lesions seen in hypertension).


The general biochemical changes that attend cellular ischemia are discussed in Chapter 1 .
Here we describe several special responses to ischemia in the CNS. [14] [15] [16] The
metabolic depletion of energy associated with ischemia can result in ____________________. 

  • inappropriate release of excitatory amino acid neurotransmitters such as glutamate, initiating cell damage by allowing  excessive influx of calcium ions through NMDA-type glutamate receptors.


Note :This elevation of cellular calcium ions can, in turn, trigger a wide range of processes including inappropriate
activation of signaling cascades, free radical generation, and mitochondrial injury. All told, these together result in cell death, mostly through necrosis.



In the region of transition between necrotic tissue and the normal brain, there is an area of at-risk” tissue, referred to as the

Note :This region can be rescued from injury in many animal models with a variety of antiapoptotic
interventions, implying that it may undergo damage by apoptosis as well.



The clinical outcome of a severe hypotensive episode that produces_____________ varies with the severity of the insult. In mild cases there may be only a transient post-ischemic confusional state followed by complete recovery
and no irreversible tissue damage. 

 global cerebral ischemia
(diffuse hypoxic/ischemic encephalopathy)


Note : However, irreversible damage to CNS tissue may occur in
some individuals who suffer mild or transient global ischemic insults.


There is a hierarchy of
sensitivity among CNS cells:______________ are the most sensitive, although glial cells
(oligodendrocytes and astrocytes
) are also vulnerable.



There is also variability in the
susceptibility of populations of neurons in different regions of the CNS (selective vulnerability),
based in part on differences in regional cerebral blood flow and cellular metabolic requirements.
With severe global cerebral ischemia, widespread neuronal death occurs, irrespective of
regional vulnerability.


Patients who survive this injury often remain in a persistent vegetative



​Other patients meet the current clinical criteria for “brain death,” including 

  • evidence of irreversible diffuse cortical injury (isoelectric, or “flat,” electroencephalogram)
  • and brainstem damage, such as absent reflexes and respiratory drive,
  • and absent cerebral perfusion


When individuals with this pervasive form of injury are maintained on mechanical ventilation, the brain gradually undergoes an autolytic process—so-called ___________________

“respirator brain.”


Border zone (“watershed”) infarcts occur in the regions of the brain or spinal cord that lies where?.

 lie at the
most distal reaches of the arterial blood supply, the border zones between arterial territories


the cerebral hemispheres, the border zone between the_____________ and ____________
distributions is at greatest risk

 anterior and the middle cerebral artery


. Damage to this region ( andterior and middle cerebral artery)  produces a ___________________ over the cerebral convexity a few centimeters lateral to the interhemispheric fissure.

sickle-shaped band of


Border zone infarcts are usually seen after_____________

 hypotensive episodes.


In the setting of global ischemia,  what is the appearance of the brain?



In the setting of global ischemia, , the gyri are____________,



In the setting of global ischemia,
and the sulci are___________ The cut surface shows poor demarcation between gray and
white matter.


In the setting of global ischemia, the brain is swollen, the gyri are widened,
and the sulci are narrowed. 


The microscopic changes of irreversible ischemic injury (infarction) are
grouped into three categories

  • Early changes
  • Subacute changes,\
  • Repair


Early changes, occurring 12 to 24 hours after the insult,
include ________________

  • acute neuronal changes (red neurons; Figs. 28-13A and Figs. 28-13B )
  • characterized at first by microvacuolization, then eosinophilia of the neuronal cytoplasm, and
  • later nuclear pyknosis and karyorrhexis. 


Similar acute changes occur somewhat later in what type of cell

astrocytes and oligodendroglia


What are the most susceptible to
global ischemia of short duration. After the acute injury, the reaction to tissue damage begins
with infiltration by neutrophils

  • Pyramidal cells in CA1 of the hippocampus (Sommer sector),
  • Purkinje cells of the cerebellum,
  • and cortical pyramidal neurons 


Subacute changes, occurring at 24 hours to
2 weeks,

  •  necrosis of tissue,
  • influx of macrophages,
  • vascular proliferation, and
  • reactive gliosis ( Fig. 28-13D ).


Repair, robust after approximately 2 weeks, is characterized
by e_____________________( Fig. 28-13E ).

  • ventual removal of all necrotic tissue,
  • loss of normally organized CNS structure, and
  • gliosis 


what is  pseudolaminar necrosis.?

In the cerebral cortex the neuronal loss and gliosis produce an
uneven destruction of the neocortex, with preservation of some layers and involvement of
others, a pattern termed pseudolaminar necrosis.


Cerebral arterial occlusion may lead to focal ischemia and, if sustained, to infarction of a
specific region within the territory of distribution of the compromised vessel.

The size, location,
and shape of the infarct and the extent of tissue damage that results are determined by
modifying factors mentioned earlier, the most impt _______________


collateral flow


The major source of collateral flow is the________________(supplemented by the external carotidophthalmic

 circle of Willis 


. 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 little if any collateral flow for the deep
penetrating vessels supplying structures such as the_________________________

  •  thalamus,
  • basal ganglia, and
  • deep white
  • matter.


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.


Occlusive vascular disease of severity sufficient to lead to cerebral infarction may be due to ______________; the basic
pathology of these conditions is discussed in Chapters 4 and 11 .

  • in situ thrombosis,
  • embolization from a distant source,
  • or various forms of vasculitides


The majority of thrombotic occlusions are due to ______________. 



The most common sites of
primary thrombosis causing cerebral infarction are the ___________, _________ and ________.

  • carotid bifurcation,
  • the origin of the middle cerebral artery,
  • and either end of the basilar artery


 The evolution of arterial stenosis
varies from progressive narrowing of the lumen and thrombosis, which may be accompanied by
anterograde extension, to fragmentation and distal embolization.

Another important aspect of
occlusive cerebrovascular disease is its frequent association with systemic diseases such as
_______________ and _____________

hypertension and diabetes.


Embolism to the brain occurs from a wide range of origins. _______________ are among
the most common sources;

Cardiac mural thrombi


What are the important predisposing factor of cardiac mural emboli?

  •  myocardial infarct,
  • valvular disease, and
  • atrial fibrillation.


Next in importance in emboli are thromboemboli arising in arteries, most often originating over atheromatous plaques within the _____________.

carotid arteries


 Other sources of emboli
include_________, particularly in children with cardiac anomalies;  ___________ and ___________. 

  •  paradoxical emboli
  • emboli associated
    with cardiac surgery;
  • and emboli of other material (tumor, fat, or air)


The territory of distribution
of the _______________—the direct extension of the internal carotid artery—is most
frequently affected
by embolic infarction; the incidence is about equal in the two hemispheres.

middle cerebral artery


Emboli tend to lodge where blood vessels _____________

branch or in areas of preexisting luminal stenosis.


______________ as in fat embolism, may occur after fractures

“Shower embolization,”


What are the manifestation of shower emobolism?

affected individuals
manifest generalized cerebral dysfunction with disturbances of higher cortical function and
consciousness, often without localizing signs


Widespread hemorrhagic lesions involving the
white matter are characteristic of embolization of _______________

bone marrow after trauma


Widespread white-matter hemorrhages are characteristic of bone marrow


A variety of inflammatory processes that involve blood vessels may also lead to luminal
narrowing and cerebral infarcts




While infectious vasculitis of small and large vessels was once
most commonly associated
with syphilis and tuberculosis, it is now more common in the setting
of __________________________.

immunosuppression and opportunistic infection (such as aspergillosis or CMV encephalitis)


____________________may involve cerebral vessels and
cause single or multiple infarcts throughout the brain.

Polyarteritis nodosa and other non-infections vasculitides 


____________ is an
inflammatory disorder that involves multiple small- to medium-sized parenchymal and
subarachnoid vessels and is 

Primary angiitis of the CNS


Primary angitis of the CNS characterize as: 

characterized by chronic inflammation, multinucleated giant cells,
and destruction of the vessel wall.



Granulomas may be found in association with the giant cells,
leading to the alternative name of granulomatous angiitis of the nervous system.

individuals manifest a ________________


diffuse encephalopathic or multifocal clinical picture, often with cognitive
dysfunction; patients improve with steroid and immunosuppressive treatment. 


Other conditions
that may cause thrombosis and infarction (and intracranial hemorrhage) include

  • hypercoagulable states,
  • dissecting aneurysm of extracranial arteries in the neck supplying the brain,
  • and drug abuse (amphetamines, heroin, cocaine)


Infarcts are subdivided into two broad groups based on the presence of_____________.



Hemorrhagic (red) infarction, characterized by ____________. 

  • multiple,
  • sometimes confluent,
  • petechial hemorrhages,
  • is typically associated with embolic events ( Fig. 28-15A )


The hemorrhage is
presumed to be secondary to reperfusion of damaged vessels and tissue, either through
collaterals or directly after dissolution of intravascular occlusive material


 In contrast,
nonhemorrhagic (pale, bland, anemic) infarcts are usually associated with _____________ Fig. 28-
15B ). 



The clinical management of patients with these two types of infarcts differs greatly as
thrombolytic therapy may be used in cases of thrombosis but is contraindicated in_______________



Thrombolytic therapy is beneficial only during a ________________ after onset of
; therefore, rapid medical attention is essential

narrow time window


A hemorrhagic infarction is present in the inferior temporal lobe of the left
side of this brain.


B, A bland infarct with punctate hemorrhages, consistent with ischemiareperfusion
injury, is present in the temporal lobe.


The macroscopic appearance of a nonhemorrhagic infarct varies with the
time after loss of blood supply.

During the first 6 hours of irreversible injury, little can be

By 48 hours the tissue becomes______________


 pale, soft, and swollen, and the corticomedullary
junction becomes indistinct.


In nonhemorrhagic infarct ,From 2 to 10 days, the brain becomes _____________


gelatinous and friable,
and the previously ill-defined boundary between normal and abnormal tissue becomes more
distinct as edema resolves in the adjacent tissue that has survived


. From 10 days to 3
weeks of NONHEMORRHAGIC INFARCT, the ___________________________

tissue liquefies, eventually leaving a fluid-filled cavity lined by dark gray tissue,
which gradually expands as dead tissue is removed


On microscopic examination of NONHEMORRHAGIC INFARCT the tissue reaction evolves along the following sequence:


  • After the first 12 hours, ischemic neuronal change (red neurons; see earlier) and both cytotoxic and vasogenic edema predominate.
  • There is loss of the usual tinctorial characteristics of white- and gray-matter structures.
  • Endothelial and glial cells, mainly astrocytes, swell, and myelinated fibers begin to disintegrate.
  • Up to 48 hours, neutrophilic emigration progressively increases and then falls off. Phagocytic cells, derived from circulating monocytes and activated microglia, are evident at 48 hours and become the predominant celltype in the ensuing 2 to 3 weeks.
  • The macrophages become stuffed with the products of myelin breakdown or blood and may persist in the lesion for months to years. 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
  • . Reactive astrocytes can be seen as early as 1 week after the insult.
  • After several months , the astrocytic response recedes, leaving behind a dense meshwork of
    glial fibers admixed with new capillaries and some perivascular connective tissue. In the
    cerebral cortex, the cavity is separated from the meninges and subarachnoid space by a
    gliotic layer of tissue, derived from the molecular layer of the cortex. The pia and arachnoid are not affected and do not contribute to the healing process. Infarcts undergo these reactive and reparative stages from the edges inward; thus, different areas of a lesion may look different, particularly during the early stages, revealing the natural progression of the response.


In the nonhemorrhagic infarct microscopic exam, what predominates in the first 12 hours?

  •  ischemic neuronal change (red neurons; see earlier) and
  • both cytotoxic and vasogenic edema predominate.


In the nonhemorrhagic infarct microscopic exam, what predominates after 48 hrs?

 neutrophilic emigration progressively
increases and then falls off.

Phagocytic cells, derived from circulating monocytes and
activated microglia, are evident at 48 hours and become the predominant celltype in the
ensuing 2 to 3 weeks.


What is the microscopic picture of hemorrhagic infarction?

The microscopic picture and evolution of hemorrhagic infarction parallel ischemic
with the addition of blood extravasation and resorption

. In individuals receiving
anticoagulant treatment, hemorrhagic infarcts may be associated with extensive intracerebral



__________are often hemorrhagic and may occur after thrombotic
occlusion of the superior sagittal sinus or other sinuses or occlusion of the deep cerebral

​Venous infarcts 


What increases the state of  ________________venous thrombosis.

  • Carcinoma,
  • localized infections,
  • and other conditions leading to a hypercoagulable state 


Spinal cord infarction may be seen in the setting of_____________ or _______________

 hypoperfusion or as a consequence of
interruption of the feeding tributaries derived from the aorta. 


Occlusion of the anterior spinal
is rarer and may occur as a result of _____________

embolism or vasculitis.


Deficits associated with infarction are determined by the ___________ involved rather than the
underlying pathologic process.

Neurologic symptoms referable to the area of injury often
develop rapidly, over minutes, and may continue to evolve over hours.

There can be
improvement in severity of symptoms associated with reversal of injury in the ischemic
penumbra as well as with resolution of associated local edema.

In general, there is often a
degree of slow improvement during a period of months. 

brain region


Because strokes are frequently
associated with atherosclerosis, many of the genetic and lifestyle risk factors are the same as
those for atherosclerotic disease.