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Flashcards in CNS pathology Deck (38):
1

Stains for CNS cells

-H&E
-Luxol blue: stains myelin blue (white matter dark blue, gray matter very light blue)
-Silver stain: stains neurofilaments black
-Immunoperoxidase stains to stain for synaptic protein (synaptophysin), localized neurofilaments or NTs

2

Ischemic cell change (red neuron)

-Red is dead, occurs in response to deprivation of O2
-Btwn 8-24hrs after insult, neuron shrinks and cytoplasm becomes eosinophilic (pink/red on H&E)
-Nucleus is darkly stained, then lost
-Changes are irreversible
-Insult requires deprivation of O2 to tissue for several minutes for irreversible damage, but then 8-24hrs is required for these changes to be observed
-Cellular changes: depletion of ATP, acidosis, impaired reuptake of GLU by glial cells and resulting excitotoxicity, accumulation of intracellular Ca, ROS generation

3

Wallerian degeneration

-Occurs when an axon is transected by trauma
-Axon and myelin distal to transection degenerate, leading to impaired axonal transport
-Disappearance of neurofibrils and breaking of axon into short fragments (parts are phargocytosed)
-This occurs over weeks in PNS and months in CNS
-Sprouting of new axons from cell body possible in PNS, but not CNS

4

Central chromatolysis

-Occurs after transection injury to neuron's axon, usually seen in large motor neurons
-Consists of swelling of cell body, dissolution of nissl substance, and migration of nucleus to the periphery of the body
-Reversible

5

Distal axonopathy

-Degeneration of the axon and myelin first develops in the most distal part of the axon
-The axon "dies back"
-Usually a result of toxins (pesticides, acrylamide, ect) or metabolic problems (diabetes, renal failure, alcoholism)
-When the metabolic needs of the cell are not met, the most distal part of the axon dies first

6

Inclusion bodies

-Abnormal deposits in neurons
-Stains w/ silver stain: cytoplasmic neurofibrilary tangles (AD) and Pick bodies (Pick disease)
-Stains w/ H&E: cytoplasmic lewy bodies (PD) and negri bodies (rabies)
-Stains w/ H&E: nuclear cowdry type A (herpes and CMV)

6

Oligodendrocytes

-All glia are neuroectodermal in origin (except for microglia, which are mesodermal- bone marrow- derived)
-Reside mostly in white matter (also some in grey) and myelin ate the axons
-Have small, round nuclei and no apparent cytoplasm

7

Myelin loss (pathologic oligodendrocytes)

-Demonstrated by luxol stain, turing myelin blue
-Demyelinating disease such as MS (autoimmune) leave large plaques of absent blue color (axons left intact)
-MS plaques are usually periventricular, larger, and more confluent that PML
-Progressive multifocal leukoencephalopathy (PML) forms small plaques of demyelination (most severe at grey-white matter junctions) when oligodendrocytes die and myelin degenerates
-Oligodendrocytes can die from viruses, like the papova virus (causes PML). This virus results in a homogenous, glassy nuclear inclusion in the oligos
-Leukodystrophies are due to genetic mutations. Myelin is abnormally formed and is unstable so it breaks down

9

Astrocytes 1

-Astrocytes present in gray and white matter, have large oval nuclei (larger than oligo's) with more euchromatin than oligo's
-Processes can only be seen when stained w/ glial fibrillary acidic protein (GFAP)
-These processes surround the small arteries of the brain and play a role in maintaining the BBB and ionic environment

9

Astrogliosis (gliosis)

-Astrocytes respond to almost any brain injury by gliosis, which includes proliferation and hypertrophy
-Cytoplasm becomes very apparent and eosinophilic due to GFAP (referred to as gemistocytes)
-This process does not result in fibrosis

10

Astrocytes 2

-Astrocytes present in gray and white matter, have large oval nuclei (larger than oligo's) with more euchromatin than oligo's
-Processes can only be seen when stained w/ glial fibrillary acidic protein (GFAP)

11

Microglia

-Derived from bone marrow (mesoderm), infiltrate developing brain along w/ blood vessels
-Slow turnover during life
-Appear as small elongated, dark-staining nuclei
-Can respond to injury by differentiating and acting as macrophages

12

Reactive microglial cell

-Activated microglia (due to brain injury or local immune response) look rod-shaped
-May up regulate expression of MHC and inflammatory cytokines

13

Macrophage response

-Microglia may differentiate into macrophages, especially during brain necrosis
-The macrophages phagocytose the tissue debris (lipid-laden macrophages, or glitter cells)
-Monocytes may enter brain after injury, and differentiate into macrophages as they do so

14

Microglial nodule

-Microglia may respond to single damaged neurons in encephalitis, by encircling the neuron and phagocytosing it (neurophagia)
-This results in the formation of a microglial nodule
-Microglial nodules may also be present in white mater, especially in HIV encephalitis

15

Multinucleated giant cell reaction

-Formed either from fusion or failure to divide
-In HIV encephalitis groups of microglial cells may accumulate in the white matter
-Some will fuse to form the multinucleate giant cell
-Can often be seen in AIDS dementia pts

16

Vasogenic edema

-Loss of integrity of BBB (broken tight junctions) may result in entrance of excess water and solutes into extracellular space of brain
-The fluid collect predominantly in white matter
-Results in increased brain volume and intracranial pressure, leads to mass effect

18

Vasogenic edema

-Loss of integrity of BBB (broken tight junctions) may result in entrance of excess water and solutes into extracellular space of brain
-The fluid collect predominantly in white matter
-Results in increased brain volume and intracranial pressure (new water entering brain)

18

Hypoxia vs ischemia

-When the brain is deprived of O2 (hypoxia) it is usually due to the brain being deprived of blood (ischemia)
-Pure hypoxia causes mostly reversible (to an extent) failure of electrical activity and synaptic transmission, and doesn't cause necrosis
-Ischemia results in decreased O2, glc, and a build up of toxic metabolites and thus is much more damaging

19

Cytotoxic edema

-Toxic or metabolic events that affect normal neuronal and glial membranes may result in intracellular accumulation of fluid, or lysing of cells
-More likely to affect cells in gray matter and usually do not lead to mass effect (not introducing any new water- just releasing the water from cytoplasm)

20

Selective neuronal necrosis (global hypoxia-ischemia)

-Cells in the CNS have differing sensitivity to hypoxia-ischemia (during intermediate severity of ischemia)
-Neurons (especially cortical neurons) are more vulnerable to ischemia than glial cells and endothelial cells (most vulnerable layers in cortex: layers 3 and 5)
-Neurons in brainstem and spinal cord are more resistant to hypoxia-ischemia than neurons in the cortex
-Water-shed areas are first to be affected because they lack sufficient collateral circulation (i.e. hippocampus), usually btwn ACA, MCA, and PCA
-Histologic changes seen only after 12-24 hrs of insult
-Results in eosinophilic ischemic necrosis: neurons shrink, cyto becomes eosinophilic, nucleus becomes blurry. Eventually the neuron disappears

21

Selective neuronal necrosis (global hypoxia-ischemia)

-Cells in the CNS have differing sensitivity to hypoxia-ischemia (during intermediate severity of ischemia)
-Neurons (especially cortical neurons) are more vulnerable to ischemia than glial cells and endothelial cells (most vulnerable layers in cortex: layers 3 and 5)
-Neurons in hippocampus most susceptible to hypoxia than another part of brain (lose recent memory)
-Neurons in brainstem and spinal cord are more resistant to hypoxia-ischemia than neurons in the cortex
-Water-shed areas are first to be affected because they lack sufficient collateral circulation (i.e. hippocampus), usually btwn ACA, MCA, and PCA
-Histologic changes seen only after 12-24 hrs of insult
-Results in eosinophilic ischemic necrosis: neurons shrink, cyto becomes eosinophilic, nucleus becomes blurry. Eventually the neuron disappears

22

Focal ischemia and infarction

-Leads to deprivation of a specific area of blood, causing excitotoxicity (increased extracellular GLU and ASP), increased lactic acid and tissue acidosis
-The center of the infarct (core) is unsalvageable
-But btwn the core and the healthy tissue is the penumbra, an area of constrained blood but partially preserved metabolism
-The penumbra is at risk of infarction, yet potentially salvageable
-Requires 12-24hrs after insult for histologic changes to be seen

23

Causes of CNS infarcts

-Atherosclerosis predominantly affects larger vessels (common carotid, especially at bifurcation, MCA, and basilar a)
-Atheroscelrotic plaques can lead to thrombotic occlusions, which do not move unless they embolize (form at site of infarction)
-Most large infarcts are caused by thromboembolisms of the MCA
-Hemorrhages are most often seen in infarcts of embolic origin

24

Microscopic features of infarcts

-Earliest changes: pallor and vacuolization (falls apart) of neuropil, endothelial swelling and eosinophilic ischemic necrosis (EIN)
-Next there are some PMNs infiltrating, followed by macrophages
-Finally there is cavitation w/ surrounding gliosis
-During gliosis and PMN/mac infiltration the brain appears hypercellular

25

Embolic vs thrombotic infarction

-Embolic infarctions are more common, and the heart is frequently the source (arrhythmias such as a fib and vulvar disease)
-Other sources: bits of thrombus, atherosclerotic plaque, talc protein, others
-The MCA is most often affected by embolic infarcts
-Embolisms are more likely to cause multiple infarcts than thrombotic
-Embolic infarcts are more likely to be complicated by hemorrhage into infarcted tissue (blood is restored to dead tissue and the capillaries hemorrhage)
-Always check for hemorrhage (indicates embolic) and multiple infarcts (indicates embolic)

26

Vasculitis infarct

-Vasculitis (inflammation of blood vessels) can cause infarction
-May be part of systemic vasculitis or isolated to CNS
-May be multiple and hemorrhagic, and has many causes (such as infection)
-Often suspected but rarely Dx
-Vessel walls infiltrated by inflammatory cells, damage to vessel wall can result in thrombosis

27

Lacunar infarcts

-Type of ischemic small vessel disease (HTN high risk factor for this and intracerebral hemorrhage)
-Small infarcts (often multiple) due to small vessel atherosclerosis w/ chronic HTN and diabetes being major risk factors
-Often found in pons and basal ganglia
-May be asymptomatic, or isolated neurological deficits (or dementia if multiple)

28

Intracerebral hemorrhage

-Associated with HTN and often occur in basal ganglia, thalamus, brainstem, or cerebellum
-Will cause a mass effect
-The ipsilateral ventricle will be small, while the contralateral one will be large due to obstruction of CSF flow
-The obstruction to CSF flow and the mass affect both raise intracranial pressure

29

Fibrinoid change

-Deposition of proteins in vessel walls, causes damage to the walls
-Due to chronic HTN (less severe, more chronic than fibrinoid necrosis)
-If extreme HTN, the vessels may undergo fibrinoid necrosis

30

Amyloid angiopathy

-Amyloid stains w/ congo red, gives a green birefringence under polarized light
-Deposition of amyloid in cerebral vessels is another way of developing intracerebral hemorrhage (sometimes multiple)
-These hemorrhages are usually located superficially in the cerebral hemispheres, with a predilection for the occipital lobe
-Common in AD

31

Cerebral aneurysm

-Can cause excruciating headaches, loss of consciousness, stiff neck, subarachnoid hemorrhage
-Blood in subarachnoid space causes: blockage to CSF flow, vasospasms (other vessels may hemorrhage)
-Often arise at bifurcations, circle of willis and communicating arteries, basilar artery
-Often are multiple and rebleed, often fatal
-Can result in intraventricular and intracerebral hemorrhage

31

Vascular malformations

-Congenital problems that cause abnormal flow, hemorrhage, seizures, and focal deficits
-Usually superficial, typically over cerebral convexity
-Can easily be seen on angiogram, where its a large bundle of unorganized vessels

32

Cavernous hemangioma

-Back-back thin walled vessels
-Located more deeply in the brain usually than AVMs
-Most common symptom is seizure by also may bleed
-Typically has less brain parenchyma btwn vessels than AVMs
-Can often be asymptomatic

33

Arteriovenous malformations (AVM)

-Congenital problems that cause abnormal flow, hemorrhage, seizures, and focal deficits
-May be asymptomatic, but are more dangerous than cavernous hemangiomas
-Usually superficial, typically over cerebral convexity
-Can easily be seen on angiogram, where its a large bundle of unorganized vessels
-Often will have arteries connecting to veins without going through a capillary bed (microscopically seen as many vessels of various sizes )
-Tend to bleed b/c arteriole blood under high pressure directly enters veinules that can't handle the pressure
-The vessel walls and size of vessels vary btwn one another (can be fibrotic)

34

Uncal herniation

-A complication of any space-occupying intracerebral lesion (mass affect), including hemorrhage and infarction
-Uncus herniates thru the incisura of the tentorium and compresses the brainstem
-Can lead to hemorrhages in the midline brainstem (duret hemorrhages- from shearing of other arteries)
-PCA can be affected by duret hemorrhages

35

Cavernous hemangioma

-Back-back thin walled vessels
-Located more deeply in the brain usually than AVMs
-Most common symptom is seizure by also may bleed
-Typically has less brain parenchyma btwn vessels than AVMs, vessels tend to be thinner (fibrosis in the walls of vessels)
-Can often be asymptomatic

36

Types of hematomas

-Epidural: lesion in the middle meningeal artery, bleeds above the dura and causes mass effect
-Subdural: lesion in the bridging vein, leads to slowly enlarging hematoma that causes mass effect
-Subarachnoid: lesion in the cerebral arteries, causes blood to enter CSF (worst headache ever, drowsiness, confusion), no mass effect
-Intracranial hemorrhage: lesion of a vessel within the brain tissue, causes mass effect

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