Introduction to Neuropathology and Mass Lesions Flashcards
Neurons
Origin
CNS/PNS
CNS: embryonic neuroectoderm
PNS: neural crest
Neurons
Gen pathophysiology
Damage to cells during development can affect neuronal number, location, connections, or function
Neuronal loss after development is completed may produce irrevocable loss of function
Exposure to insults/diseases throughout life may lead to accumulation of damage (chemicals, toxins, radiation, etc.)
Neurons are highly susceptible to metabolic insults (hypoxia, ischemia, hypoglycemia)
Wernicke Encephalopathy
What does it affect
Wernicke encephalopathy involves damage to neurons and their connections in mammillary bodies, hypothalamus, and other periventricular gray matter.
Wallerian degeneration
def
Degeneration of axon distal to site of axonal injury
Trans-synaptic degeneration
Retrograde/anterograde
retrograde: loss of synaptic target cell leads to death of afferent neuron
anterograde: loss of afferent cell leads to death of target neuron
Supporting cells (chart)
Normal function/special features
astrocyte
Normal Function
provides structure, boundaries, milieu, contributes to blood-brain barrier
Special Features
makes glial fibrillary acidic protein (GFAP), reacts to injury
Supporting cells (chart)
Normal function/special features
oligodendrocyte
Normal Function
Makes CNS myelin
Special Features
Makes CNS myelin proteins (MBP, MAG, etc) and lipids
Supporting cells (chart)
Normal function/special features
Ependymocyte
Normal Function
Lines ventricles
Special Features
Cilia contribute to CSF flow
Supporting cells (chart)
Normal function/special features
Choroid plexus
Normal Function
Makes CSF
Special Features
Forms blood/CSF barrier
Supporting cells (chart)
Normal function/special features
Microglia
Normal Function
Immune Cells belonging to mononuclear phagocytic lineage (monocytes)
Special Features
React to injury, phagocytic, can become macrophages
Supporting cells (chart)
Normal function/special features
Schwann Cell
Normal Function
Makes PNS myelin, support peripheral ganglion cells (satellite cells)
Special Features
Makes PNS myelin proteins and lipids
Useful marker of CNS injury
Astrocytes which react to pathologic stimuli and thus are useful makers of CNS injury
Astrocytosis
def
ASTROCYTOSIS: refers to the acute reactive changes of hypertrophy and hyperplasia
Gliosis
def
GLIOSIS: refers to chronic changes of “glial scar”, representing increase in astrocytes and their cell processes filled with GFAP.
NOTE: Significant loss of CNS neurons and glial cells from injury or disease results in atrophy or even cavitation (parenchymal cavities filled with interstitial fluid and lined by gliotic adjacent brain tissue). Fibrocollagenous scar formation is rare in the CNS except in trauma and destructive conditions such as abscesses.
Metabolic astrocytosis
def
(also known as Alzheimer type 2 change): proliferation and enlargement of gray matter astrocytes in response to metabolic injury, e.g., hepatic failure, renal failure, others.
Demyelination
Primary/secondary
primary demyelination: selective destruction of myelin with sparing of axon e.g., multiple sclerosis (CNS), Guillain-Barré (PNS)
secondary demyelination: breakdown of myelin occurs secondary to loss or destruction of axon (e.g., in Wallerian degeneration).
Dysmyelination
def
def formation of abnormal myelin; occurs in some inherited metabolic diseases (e.g., certain leukodystrophies)
Remyelination
def
Remyelination
def (reformation of destroyed myelin following demyelination) is generally poor in the CNS but can occur readily in PNS and reconstitute normal myelin sheath.
Fluid compartments in the brain
list
Fluid compartments in the brain include intravascular, CSF spaces/ventricles, extracellular (interstitial) fluid, and intracellular fluid.
CSF
Production/reabsorption
location
The brain is bathed in CSF, a clear colorless low-protein fluid produced by the choroid plexus in the ventricles.
CSF circulates through ventricles, passes into the subarachnoid space, and is resorbed by arachnoid granulations and returned to the venous system. It serves to provide a suitable environment for brain function and helps to cushion the brain from injury.
Normal values of CSF
Protein/glc/Na/Cl/K/Leukocytes
Protein
5-15mg/100ml ventricle
15-45 mg/100ml
Glc
45-80 mg/100ml
Na
142-150 mEq/L
Cl
120-130 mEq/L
K
2.2-3.3 mEq/L
Leukocytes
0-5/mm3 (usually mononuclear
Physiological parameters
Pressure/total CSF volume/rate of secretion
Pressure
70-220 mm H20
Total CSF volume
100-150ml
Rate of Secretion
0.5L/day (constant, not dependent on ventricular pressure)
Examination of CSF
Common pathologic changes
xanthochromia: yellow color, due to degenerating RBC’s, high protein
cloudiness: due to increased protein, WBC’s
elevated protein: due to infection, tumor, tissue destruction
pleocytosis/leukocytosis: increased WBC’s due to inflammation, infection
Hydrocephalus
Def/tx
Enlargement of the ventricles by CSF
Hydrocephalus is commonly treated by insertion of a catheter (“shunt”) into the ventricle with the other end placed in a body cavity like the peritoneum.
Hydrocephalus
types
Obstructive (non-communicating or internal)
Results from blockage of CSF flow w/in the ventricular system
Non-obstructive (communicating or external)
Results from impaired flow or resorption of CSF outside of the ventricular system
Ex Vacuo
compensatory enlargement of ventricles due to loss of brain parenchymal volume (atrophy): CSF occupies space once occupied by brain parenchyma. ICP is normal
Normal pressure hydrocephalus
uncommon syndrome of progressive dementia, urinary incontinence, and disordered gait associated with ventricular enlargement but relatively normal ICP.
BBB
Pathophysiologic significance
normal BBB acts as physiologic barrier preventing ingress of most large or charged molecules, e.g., many drugs cannot pass through the normal BBB
BBB is thought to mature later in gestation but is generally present at birth: recall that bilirubin in premature infants with hyperbilirubinemia can pass into the CNS and cause damage to the basal ganglia (kernicterus)
BBB breakdown occurs from many forms of inflammation or injury and can be recognized by neuroradiologists using “contrast agents”; this is known as “enhancement” and facilitates recognition of lesions on CT or T1 MRI scans
Brain edema
classifications
vasogenic edema: predominantly affects white matter and is due to increased interstitial fluid resulting from BBB breakdown, e.g., caused by inflammation, tumor, etc.
cytotoxic edema: predominantly affects gray matter and reflects cellular swelling resulting from cell membrane ion pump dysfunction (usually due to energy failure), e.g., hypoxic/ischemic injury to neurons or glia
periventricular interstitial edema: predominantly affects periventricular white matter and results from increased ventricular pressure (obstructive hydrocephalus)
Intracranial compartment
components
TISSUE: meninges, brain parenchyma & interstitial fluid (~80%)
VASCULAR: blood vessels and intravascular blood (~10%)
CSF: intraventricular, interstitial, and subarachnoid (~10%)
Monro-Kellie Hypothesis
Increased intracranial pressure ( ICP): Because the brain is confined within a rigid container (skull), any increase in one of the intracranial components (tissue, blood, CSF) must occur at the expense of the other two in order to maintain normal ICP. This is known as the Monro-Kellie hypothesis. When the compliance of the three components is exceeded, ICP begins to rise exponentially, if volume continues to increase.
CPP
equation
CPP = MAP – ICP
CPP
autoregulation
Cerebral perfusion pressure (CPP) is autoregulated to remain stable. CPP = MAP (mean arterial pressure) – ICP. Up to a point, the body can maintain CPP by increasing MAP and dilating cerebral blood vessels. When ICP exceeds MAP, perfusion becomes inadequate to maintain brain function.
Clinical Manifestations of ICP
- headache (especially morning headache)
- projectile vomiting
- papilledema and loss of vision
- cardiorespiratory physiologic changes (“Cushing response”) sinus bradycardia irregular respirations (Cheyne-Stokes) systolic hypertension
- decline in level of consciousness (drowsiness progressing to coma)
- neurogenic pulmonary edema
- focal neurologic signs due to tissue shifts (e.g., dilated pupil)
Rising ICP
causes
parenchyma: tumors, edema, inflammation, abscess
blood: hemorrhage, increased venous pressure, increased intra-arterial volume
CSF: overproduction, blockage of CSF flow or resorption
↑ ICP
tx
usually treated by creating hyperventilation-induced hypocarbia, by administering intravenous mannitol to create an osmotic gradient, by administering barbiturates, or by administering corticosteroids to correct vasogenic edema. The exact mechanisms of some of these interventions are poorly understood.
Herniations
progression
When intracranial pressure exceeds arterial perfusion pressure, vascular perfusion stops and ischemia and brain death ensue. If the comatose patient is maintained on life support, the dead, non-perfused brain then undergoes autolysis (known as “respirator brain”). Such individuals show the clinical syndrome of “brain death”. In some individuals, enough brainstem/hypothalamic function may persist to permit spontaneous ventilation, autonomic control, sleep-wake cycles, and even preservation of eye movements, but usually without conscious awareness (“persistent vegetative state”).
Cerebral herniation’s (chart)
Herniated part/opening/effects
Cingulate
Herniated Part
Opening
Effects
Cingulate gyrus
Subfalcine
Compression of anterior cerebral artery
Cerebral herniation’s (chart)
Herniated part/opening/effects
Uncal (asymmetric)
Herniated Part
Opening
Effects
Uncus (medial temporal lobe)
Tentorial incisure
Compression of midbrain & CN III: coma, dilated pupil, duret hemorrhage
Cerebral herniation’s (chart)
Herniated part/opening/effects
Central (asymmetric)
Herniated Part
Opening
Effects
Dienchephalon & medial temporal lobes
Tentorial incisure
Compression of thalamus & midbrain: coma, posturing, hydrocephalus
Cerebral herniation’s (chart)
Herniated part/opening/effects
Tonsillar
Herniated Part
Opening
Effects
Cerebellar tonsils & medulla
Foramen magnum
Compression of medulla: apnea, acute hydrocephalus, loss of consciousness
