72. Pathological Responses to Brain Injury Flashcards
What do the following cells normally look like on histology?
- neurons
- oligodendrocytes
- astrocytes
- microglia
- ependyma
Neurons: (pyramidal neurons in layers 3/5), large triangular cell bodies, abundant cytoplasm, large nucleus, prominent nucleolus (Nissl substance: rouch ER, bluish granules)
Oligos: round dark nuclei with perinuclear halo (more common in white matter)
Astros: oblong nuclei with fine chromatin, cytoplasm blends in with background (white and grey matter)
Microglia: activated = rod cells (thin, elongated, dark nuclei)
Ependyma: single layer of cuboidal/columnar ciliated cells - line ventricles for blood-csf barrier
How do neurons change in response to injury over time?
How do cells change due to axonal injuries?
What do different types of neuronal inclusions suggest?
- Acute (12hrs-2days later): RED DEAD Neurons - earliest sign of irreversible neuronal injury (cell shrinkage, RED cytoplasm, pyknotic (small,dark) nucleus)
- Subacute/Chronic (2d-10d): “DEGENERATION” - reactive gliosis (astrocyte hyperplasia/hypertrophy)
Axonal Damage: cell body rounding/ballooning, CENTRAL CHROMATOLYSIS (Nissl Body dispersion to periphery)
Rabies: cytoplasmic Negri bodies
Herpes: intranuclear Cowdry bodies
Proteinopathies: aggregates of misfolded proteins in cytoplasm and nucleus
PD: Lewy Body; AD = neurofibrillary tangles
How do astrocytes change in response to injury?
What are Alzheimer Type 2 Astrocytes?
What are Rosenthal Fibers?
What is Corporal Amylacea?
- Gliosis - MOST COMMON response of CNS to Injury (1 week later) - hypertrophy (abundant eosinophilic cytoplasm)/hyperplasia (eccentric nuclei) of astrocytes, filling space of neurodegenerative disease; visualized with GFAP stains
Alz T2: NOT with AD; in pts with long-standing METABOLIC DISORDERS - Enlarged nuclei (3x) with light chromatin/nucleolus, (no eosinophilic cytoplasm)
Rosenthal Fibers: cytoplasmic inclusions in astrocytic processes - in areas of long-standing gliosis (cyst walls) and slow growing tumors)
Corpora Amylacea: in aging/long-standing injury - degenerative changes (round, blue/basophilic, concentrically layered structures of astrocyte end processes, calcified)
What 3 days do microglia change in response to injury?
- Activate = Rod Cells
- Microglial Nodules = aggregates around areas of necrosis (Giant Cells = HIV Encephalitis)
- Neuronophagia = surround dying neurons (seen in polio/ALS)
What do injured oligos represent?
What inclusions are in oligos?
What does injured ependyma look like?
Injury - demyelinating disorders/leukodystrophies
Inclusions - PML - nuclear; Cytoplasmic - MSA
Ependymal Granulations: nonspecific to injury, form ependymal canals
Inclusions: CMV/Viral
What are the types of Cerebral Edema?
What does cerebral edema look like macroscopically?
- Vasogenic Edema = High Extracellular fluid: disrupted BBB has more permeability
- Cytotoxic Edema = High Intracellular fluid: 2/2 injury of cells disrupting ion gradiant
both types COEXIST
Gross: Gyri-flattening, Sulci-narrowing, Ventricular System Compression
Hydrocephalus: what it is, causes, 2 main types
High CSF volume 2/2 disequilibrium b/w CSF formation and resorption
Cause: impaired flow/absorption
1. Noncommunicating: obstructive, CSF blocked from reaching SubArachnoid - enlargement proximal to blockage
2. Communicating: enlargement of ENTIRE CSF system (due to choroid plexus papilloma - overproduction; scarring of arachnoid granulations from hemorrhage)
Herniation: what is it - 3 types
Displacement of tissue past dural partitions in skull or through skull openings
- Subfalcine (Cingulate) Herniation: cingulate gyrus goes under falx cerebri - can compress ipsi ACA
- Transtentorial (Uncal) Herniation: uncus/medial temp lobe through tentorium - compress ipsi CN3, PCA, cerebral peduncle (severe - push contralateral cerebral peduncle)
- Cerebellar tonsillar herniation: LIFE THREATENING - cerebellar tonsils through foramen magnum - compression of medulla’s cardio/resp centers
Duret Hemorrhages: rupture of BA perforators to pons due to transtentorial herniation
Causes of Focal Cerebral Ischemia (and where they most likely impact cerebrum)
- Embolism from distant source (affects MCA most - continuation of ICA)
- In situ thrombosis - atherosclerosis/plaque rupture - at carotid bifurcation, origin of MCA, either end of BA
- inflammatory process in vessels
Global Cerebral Ischemia
- causes
- most sensitive/vulnerable areas
Generalized reduction in CBF causes diffuse hypoxic-ischemic encephalopathy
Neurons are MOST SENSITIVE to any form of injury
1. Pyramidal neurons in CA1 region of HIPPOCAMPUS
2. Cerebellar Purkinje Neurons
3. Watershed Regions in cortical layers 3/5
Macroscopic Findings of Non-Hemorrhagic Infarcts (what happens grossly over time)
- Acute (AFTER 8 hours - 2 days)
- blurring of grey-white junction, duskiness/softening of tissue - Subacute (2-10d)
- prominent softening, grey-white blurring, dusky discoloration, edema
- tissue becomes progressively more gelatinous/friable
- boundary becomes more distinct - Resolving Infarct (10days - months)
- liquefactive necrosis (gelatinous/friable) with progressive cavitation - Remote Infarct (months - life)
- CSF filled cystic cavity
Microscopic Findings of Non-hemorrhagic Infarcts (what happens histologically over time)
- Acute Infarct (AFTER 12 hrs - 2 days)
- RED DEAD NEURONS (irreversible damage)
- Edema, influx of neutrophils - Subacute Infarct (2-10days)
- Lipid Laden Macrophages predominate
- Gliosis and capillary proliferations appear at 1 week and move inward - Resolving Infarct (10d - months)
- liquefactive necrosis: removal of necrotic tissue by macrophages
- progressive cavitation, surrounding gliosis, vascular proliferation - Remote Infarct (months - life)
- some macs remain, cystic cavity with dense rim of reactive astrocytes
- subpial tissue may remain intact
Lacunar Infarcts
- where are they
- what is the biggest risk factor
- what structure is most commonly involved?
small, perivascular, ischemic, cavitary infarcts
RF: HTN (causes arteriosclerosis with vessel occlusion of deep penetrating vessels)
Location: PUTAMEN
What are the 3 types of Intraparenchymal Hemorrhage? (list)
- Ganglionic Hemorrhage
- Lobar Hemorrhage
- Secondary Hemorrhagic Infarcts
Ganglionic Hemorrhages
- what are they, most common etiology
- Gross features
- Histo features
Deep, grey/white matter (usually PUTAMEN)
Etiology: HTN
Gross
- Acute: hematoma (core of clotted blood) compressing surrounding parenchyma
- Subacute: hematoma resorption, surrounding ischemic tissue becomes gelatinous/friable
- Resolving: liquefactive necrosis, cavitation
- Remote: cavitary lesion with BROWN RIM (hemosiderin-laden macrophages)
Histo:
- Acute: central hemorrhage and RED DEAD neurons
- Subacute: influx of hemosiderin/lipid - laden macrophages, hematoma resorption, gliosis/vascular proliferation
- Resolving: liquefactive necrosis, cavitation/gliosis
- cavitary lesion lined by gliosis + hemosiderin-laden macrophages