CNS-I Flashcards
1
Q
Astrocytes
A
o Acts as metabolic buffers and detoxifiers within the brain
o Modulate how neurons communicate
2
Q
Oligodendrocytes
A
o Produce a fatty substance called myelin which is wrapped around axons as layer of insulation (increases conduction)
3
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Ependymal cells
A
o Line the spinal cord and ventricles of the brain
o involved in producing CSF
4
Q
Microglia
A
o Resident macrophages (involved in neuro-inflammation)
5
Q
Sensory information enters the CNS through peripheral nerves and is conducted immediately to:
A
o The spinal cord at all levels o Medulla, pons and mesencephalon o The cerebellum o The thalamus o Areas of the cerebral cortex
6
Q
The most important role of the nervous system is to
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control the various bodily activities
7
Q
The nervous system controls various bodily activities through three mechanisms
A
o Contraction of skeletal muscles through out the body
o Contraction of smooth muscles in the internal organs
o Secretion of active chemical substances by both exocrine and endocrine glands
8
Q
Muscle glands are known as the
A
effectors
9
Q
What sends signals to control the Spinal cord level ?
what responses does the spinal cord level produce?
A
o The upper levels of the nervous system send signals to the control centers of the cord
→ Movement, reflexes -like when you touch a hot stove
10
Q
Lower Brain or Subcortical Level function??
Its composed of?
A
o Subconscious activities of the body are controlled in the lower areas of the brain
→ The medulla, pons, hypothalamus, thalamus, cerebellum, and basal ganglia
11
Q
Higher Brain or Cortical Level
A
o Without the cerebral cortex, the functions of the lower brain’s centers are not often accurate
o The cerebral cortex cannot function by itself
12
Q
Ascending Reticular Activating System (ARAS)
A
o In the brainstem from the medulla to the diencephalon
o Relays innervation from the environment stimuli to the thalamus and then to the cerebral cortex (midbrain?)
13
Q
Functions of the cerebral cortex
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o Thinking, learning, and remembering
14
Q
Functions of the Thalamus
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o Interprets certain sensory messages such as those of pain, temperature, and pressure
15
Q
Functions of the Hypothalamus
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Controls various homeostatic functions – body temp, respiration, and heartbeat
16
Q
Functions of the Cerebellum
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Contributes to muscle tone, posture, and balance
17
Q
Functions of the Brain Stem
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o Regulates heartbeat and breathing
→ This is why its instant death if your brainstem is injured
o Plays a role in consciousness
18
Q
CSF production
A
o By the choroid plexus of each ventricle
→ choroid composed of Ependymal cells
19
Q
CSF functions
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o Acting as a cushion or “shock absorber”
o Deliver nutrients to the brain and removing waste
o Flow between the cranium and spine, compensate for changes in intracranial blood volume
20
Q
Blood-brain barrier (BBB):
A
A series of high-resistance, tight junctions between endothelial cells as well as astrocytes with processes on capillary walls → charged big molecules can’t cross
21
Q
Blood-CSF barrier:
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Formed by tight junctions between choroid epithelial cells
22
Q
Both the BBB and the blood-CSF barrier
A
o Endothelial cells and astrocytes that make up the BBB and cells forming the blood-CSF barrier can produce cytokines
o Astrocytes can act as antigen-presenting cells that curb the immunologic response to CNS infections
23
Q
• Wallerian degeneration in PNS (spinal nerves are part of the CNS)
A
o Occurs in the axon distal to the site of a cut
A. Normal nerve innervating skeletal muscle
B. The nerve has been transected and Wallerian degeneration has begun (corresponding atrophy in the muscle)
C. Proximal nerve terminals send sprouts toward the Schwann cells
D. Some of the sprouts make it into tubes and re-innervate the muscle
24
Q
• Wallerian degeneration in CNS
A
o Damage occurs to Spinal cord axons
o Macrophages (purple) enter to clear the debris and astrocytes begin to enlarge and proliferate
o A glial scar is formed blocking axonal growth
25
Astrocytes reaction in injury to the glia
o Acute cell injury, such as hypoxia, hypoglycemia, and toxic injuries causes cellular swelling
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Oilgodendrocytes reaction in injury to the glia
o Injury or apoptosis of oligodendrocytes is a feature of acquired demyelinating disorders
Not producing myelin at all or producing it incorrectly
27
Intracranial components:
o Cerebral parenchyma (80%)
→ Brain tissue
o CSF (10%)
o Blood (10%)
28
Definition of intracranial pressure?
What is normal?
What is pathologic?
o The pressure inside the cranial cavity
o Normally <15mmHg in adults, and
Pathologic intracranial hypertension (ICH) is ≥ 20mmHG
29
How does the brain accommodate an increase in ICP?
Displacement of CSF into the thecal sac
→ Membrane that covers the cauda equina
o Decrease in the volume of the cerebral venous blood by venoconstriction and extracranial drainage
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o The relationship between intracranial volume and pressure is
is nonlinear
| • As pressure goes up and compensation gets overwhelmed we have much more increase in pressure
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o Normal Pressure Hydrocephalus (NPH)
o Pathologically enlarged ventricular size (compensation) with normal pressures on lumbar puncture
Because your ventricles are dilated you have normal pressure
o NPH is a form of communicating hydrocephalus and is different from obstructive or non-communicating hydrocephalus
Because there is nothing blocking CSF and blood flow
o Shunt placement can decrease CSF accumulation and symptoms resolve
32
• Pathophysiology: Normal Pressure Hydrocephalus (NPH) is idiopathic, but what are their theories?
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o Idiopathic NPH
Cerebrovascular disease:
→ HTN, Coronary Artery Disease and Peripheral Arterial Disease
Decreased CSF absorption
→ Leads to accumulated CSF dilated ventricles
Increased central venous pressure
→ Due to lung and heart failure
Neurodegenerative disorder
→ Ex: Alzheimer’s Disease
```
33
Secondary NPH can be caused by?
Intraventricular or subarachnoid hemorrhage (either from aneurysm or trauma) and prior acute or ongoing chronic meningitis
34
What is the Clinical Triad of NPH?
- Wet, Wacky, and Wobbly
• Gait Difficulty
o Can’t separate gaits from each-other
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• Cognitive deficits
o Psychomotor slowing
o Decreased attention and concentration
o Impaired executive function
o Apathy (lack of interest, enthusiasm, or concern)
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• Urinary incontinence
35
What occurs in the brain that is a direct result of Increased ICP
↑ ICP → ↓ blood flows → decreased blood perfusion to the brain → cerebral edema
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• Global symptoms of elevated ICP:
o Headache
o Decreased consciousness
o Vomiting
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• Focal Symptoms of elevated ICP
o Herniation
| The displacement of brain tissue through opening in the skull (goes to another location it’s not supposed to be)
38
Herniation can occur in three three common clinical settings:
Cerebral edema
Increased CSF volume (hydrocephaluswhen its non-communicating)
Mass lesions (tumors in the brain)
39
Tonsillar herniation:
• It causes brainstem compression and it compromises vital respiratory and cardiac centers in the medulla (Puts pressure on the brainstem)
40
Cerebral Blood Flow/Perfusion and Autoregulation
o Cerebral blood flow is maintained at a relatively constant level
o Maintenance of cerebral blood flow by autoregulation within a mean arterial pressure range of 60 to 150mmHg
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• At about 180 mmHg, autoregulation fails causing:
o Cerebral vasodilation and cerebral edema
42
• Cerebral Perfusion Pressure:
o Cerebral perfusion pressure (CPP) is a clinical surrogate for cerebral perfusion
o CPP is defined as mean arterial pressure (MAP-blood pressure) minus ICP
o CPP= MAP-ICP
43
• What are the two types of Cerebral Edema and what are they caused by?
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o Vasogenic Edema: irreversible increase in EXTRAcellular fluid (coming from blood vessel)
Caused by:
• BBB disruption
• Increased vascular permeability
• No tight junctions
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o Cytotoxic edema: potentially reversible increase in intracellular fluid secondary to neuronal, or glial, or endothelial cell membrane injury (blood vessels are fine-swelling happens inside the cell)
Caused by:
• Hypoxia/ischemia
44
Hypoxic-Ischemic Brain Injury causes?
o Cardiac arrest
o Vascular Damage
o Poisoning
o Head trauma
45
Mechanisms of Ischemic Cell Injury and Death
• Part of the brain parenchyma (tissue) core undergoes immediate death
• While others may only be partially injured with potential to recover (penumbra-tissues at risk)
o 50 mL/100g/min of cerebral blood flow
Inhibition of protein synthesis
o 35 mL/100g/min of cerebral blood flow
Protein synthesis ceases. Glucose utilization transiently increases
o 25 mL/100g/min of cerebral blood flow
Onset of anaerobic glycolysis. Tissue acidosis
o 17 mL/100g/min of cerebral blood flow
Neuronal electrical failure
o 11 mL/100g/min of cerebral blood flow
Membrane failure
o Anything less is cell death
46
Cerebrovascular Disease
o Pathophysiological process involving the blood vessels of the brain
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Cerebrovascular Disease classification
o The process may be intrinsic to the vessel
o The process may originate remotely
Embolism
o The process may result from decreased cerebral blood flow
↑ ICP
o The process may result from rupture of a vessel in the subarachnoid space or intracerebral tissue
Aneurysms
48
Cerebrovascular disease can lead to?
• *Can lead to transient ischemic attack (TIA) or Ischemic stroke
o Doesn’t necessarily mean infarction of the brain
• **Can lead to primary hemorrhagic stroke
49
*******CHARACTERISTIC OF STROKE SUBTYPES CHART
look at powepoint
50
Definition of TIA:
o A transient episode of neurologic abnormalities caused by focal brain, spinal cord, or retinal ischemia, without acute infarction
Could be infarction (less of a chance)
51
• Definition of ischemia stroke:
o An infarction of brain, spinal cord, or retinal cell death due to ischemia, based on neuropathologic, neuroimaging, and/or clinical
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o Embolic TIA
o Embolic TIA
Thrombosis goes to the brain
*Important to find out origin of emboli (to prevent anymore further event)
53
o Large artery, low-flow TIA:
Often associated with an atherosclerotic lesion
54
o Lacunar or small penetrating vessel TIA caused by stenosis
Lacunar are tiny vessels that are very prone to stenosis so very prone to TIA’s
55
• High risk lesions regarding low-flow or embolic TIA’s:
o Atherothrombotic lesions at the origin of the internal carotid artery that are narrowed more than 50%
o Atherothrombotic lesions at the basilar artery
o Emboli to basilar artery
o Dissection lesions at internal carotid artery or as it enters the foramen transversarium
56
• Intraparenchymal brain hemorrhage (IPH)
o Develops from tears in the brain tissue and/or vasculature
Not related to any trauma just issues with the blood vessels inside the brain
57
• Subarachnoid hematoma (SAH):
o Non-traumatic causes (could be
| o The most common is an aneurysm*** (worst headache of patients life if they survive)
58
Two major causes of Subdural hematoma (SDH):
o Two major causes
Damage to the bridging veins
Tearing of cortical veins
59
• Epidural Hematoma (EDH) AKA extradural hematoma
o A blunt trauma may tear the middle meningeal artery
60
Atraumatic/Spontaneous Intracranial Hemorrhage (ICH)
| leads to?
leads to ↑ICP
61
Atraumatic/Spontaneous Intracranial Hemorrhage (ICH) etiology?
Hypertensive vasculopathy
62
Atraumatic/Spontaneous Intracranial Hemorrhage (ICH) clinical presentations?
o Signs and symptoms ICH depend on the location and size of the hemorrhage
o The neurologic symptoms and signs usually increase gradually over minutes or a few hours
o Headache, vomiting, and a decreased level of consciousness
63
Atraumatic/Spontaneous ICH Pathogenesis
| 3 ways
• Cerebral microbleeds:
o HTN→ Necrosis + hyperplasia of blood vessels permeability
Microscopic pseudoaneurysm formation with subclinical leaks of blood
• Hemorrhage enlargement:
o Associated with neurologic deterioration and worse outcomes
• Brain Damage
64
Primary Brain Damage after ICH
o Parenchymal blood accumulation
Tissue disruption
Mechanical damage due to mass effect
Elevated ICP
→ damaged BBB causes edema
65
Secondary brain damage
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o Thrombin activation
o Lysis of RBC’s causes the release of hemoglobin, which is converted to heme and iron
By oxidative stress
o Inflammatory reaction
Release of proinflammatory mediators
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66
Neural Tube Defects (NTD’s)
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o Neural tube defects (NTD’s) are one of the most common congenital anomalies, and are the cause of chronic disability
o Myelomeningocele (spina bifida) is the most common NTD
Thicken ectoderm makes neural plate → groove→ tube, BUT if tube doesn’t close → neural tube defect
```
67
spina bifida aperta?
A cleft in the vertebral column, with a defect in the skin → meninges and spinal cord are exposed aka “open spinal dysraphism” or
68
o Closed Spinal dysraphism aka “occult spinal dysraphism” or spina bifida occulta”
is a cleft in the vertebral column, without a skin defect, and neural tissue is not exposed
69
Open and closed spina bifida is caused by?
o Multifactorial origin
| o Folate deficiency during the first several weeks of gestation
70
Myelomeningocele’s Neurological Abnormalities
o Chiari II malformation
→ Downward displacement of the cerebellum and medulla abnormalities in cognitive function
→ This obstructs flow of CSF which leads to Hydrocephalus
o Spinal Cord
→ Typically affect the trunk, legs, bladder, and bowel complete paralysis and absence of sensation
o Brain stem:
→ Due to the chiari malformation → swallowing difficulties, vocal cord paresis
71
Cerebral Palsy
o Permanent non-progressive central motor dysfunction that affect muscle tone, posture, and movement
72
Cerebral Palsy Etiology
o Most cases due to prenatal factors, but peri- and postnatal factors or events can also contribute
o Prematurity and low birth
73
Pathogenesis of Cerebral Palsy
Pathogenesis of Cerebral Palsy
• Focal white matter injuries are produced at a specific locus in the white matter such as:
→ Periventricular white matter
74
What is Periventricular leukomalacia (PVL)?
Where does it most often occur?
o Definition: is the necrosis of the white matter near the lateral ventricles
Most often occurs in premature infants
75
what causes Periventricular leukomalacia (PVL) ?
Decreased oxygen/blood flow to the periventricular region of the brain
Damage to the glial cells
76
Three types of brain injuries and their symptoms
-In the front lobe: clinically silent
Not really symptoms
-Severely in the spinal cord: disabling
-In the brainstem: fatal
77
A GCS score: ?
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Traumatic Brain Injury (TBI)
• Definition:
o A heterogeneous disease
o A GCS score: (clinical way of categorizing severity)
13 to 15 mild traumatic brain injury
9 to 12 moderate
8 or less severe
o LOWER THE SCORE IS THE WORSE IT IS
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78
• Pathophysiology of TBI
| -• Primary brain injury ?
o Tissue shearing at the interface of grey and white matter known as diffuse axonal injury (DAI) leads to axonal swelling
o Cerebral contusions
o Extra-axial hematomas
Epidural, subdural, subarachnoid, hemorrhage and intraventricular
79
Secondary Brain Injury causes?
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o Excitotoxicity
o Electrolyte imbalances
o Inflammatory responses
o Apoptosis
o Secondary Ischemia
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80
• Acute Mild TBI: Concussion classification?
o A Glasgow Coma Scale (GCS) score of 13 to 15, measured at approximately 30 minutes after the injury
81
Acute Mild TBI: Concussion pathophysiology
o Mild TBI results from direct external contact forces or from acceleration/deceleration trauma
o The acute clinical symptoms are related to functional rather than structural injury
82
• Clinical Manifestations: of acute mild TBI: concussion
o Confusion and amnesia
83
Complicated Concussion: Contusion: defintion
o Brain contusions are areas of injury with localized ischemia, edema and mass effect
o Mild TBI can be complicated by ongoing cortical contusions and intracranial hemorrhage
o Brain contusions may delay recovery from a concussion
84
• Chronic Traumatic Encephalopathy (CTE): definitiion
Definition
o One of the sequelae of Mild TBI
o A dementing illness that develops after repeated concussions (head trauma)
85
Chronic Traumatic Encephalopathy (CTE): Etiology?
o Sports-related concussion (contact sports)
| o Combat-related TBI (military)
86
Chronic Traumatic Encephalopathy (CTE): Neuropathy
• Neuropathology:
o Tau-immunoreactive degenerative changes that are distinct from Alzheimer’s Disease in their preferred distributive in the superficial cortical layers
→ CTE distribution is different
87
how does Infection damage the central nervous system?
• Infection may damage the nervous system:
o Directly through injury of neurons or glia by the infectious agent
o Indirectly through microbial toxins
o The destructive effects of the inflammatory response
o The result of immune-mediated mechanisms
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Microbes can access the CNS by:
o Hematogenous spread (BLOOD VESSELS): most common
o Direct implantation
o Local Extension
o Peripheral Nerves
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Meningitis
inflammatory of the leptomeninges within the subarachnoid space
90
Classification of meningitis:
o Acute pyogenic (usually bacterial)
Harder to treat due to their virulence factors
o Aseptic (usually viral)
o Chronic (usually tuberculous, spirochetal, or cryptococcal)
91
Meningoencephalitis:
o Inflammation of the meninges and brain parenchyma
92
Etiology: of meningitis
o Mainly in adults: Streptococcus pneumoniae and Neisseria Meningitidis
93
Pathogenesis of Bacterial Meningitis
• Colonization (in mucous membrane of meninges): IgA protease inactivates the mucosal antibody (IgA)→ bacterial attachment to host cells
• Invasion: cross the respiratory epithelium and invade the blood
• Intravascular survival: by avoidance of the complement system
• Meningeal Invasion: cross the BBB
o Bacterial pathogens get rid of the tight junctions
94
• Pathophysiology of Meningitis
• Inflammation get ride tight junctions in BBB → ↑ BBB permeability → Vasogenic edema (due to failure in autoregulation)→ ↑ICP→ ↓blood perfusion (altered cerebral blood flow) → ischemia → release of ROS species’ → Neuronal damage
95
Aseptic Meningitis (Viral) defintion?
o Patients who have clinical and laboratory evidence for meningeal inflammation with negative routine bacterial cultures
96
Etiology of aseptic meningitis
o Enteroviruses
97
clinical presentation of aseptic meningitis
o Similar presentation to that of bacterial meningitis, but its self-limited
Goes away by itself, no antibiotics needed
98
Clinical Features and Pathophysiology of each clinical feature of Meningitis
• Fever
o Cytokines affect the thermoregulatory neurons of the hypothalamus changing the regulation of body temp
• Headache
o Bacterial exotoxins, cytokines, and ↑ICP stimulate nociceptors in the meninges
Nociceptors are sensory receptors for painful stimuli
• Stiff Neck
o Flexion of the spine→ stretching of meninges→ leads to pain in neck→ causing limited ROM
• Altered Mental Status
o ↑ ICP → brain herniation → damage to ARAS
ARAS: system that controls alertness in brain stem
• N/V
o ↑ ICP on the Medulla oblongata
Vomiting center
CTZ- chemoreceptors on bottom of 4th ventricle close to BBB
99
when part of the brain parenchyma undergoes immediate death
core
100
partially injured parenchyma with potential to recover
penumbra
