pathophys 2 test 3 all pts combined

Central Nervous System

• Consists of brain and spinal cord

Peripheral Nervous System

• Consists of cranial nerves (project from brain) and spinal nerves (project from spinal cord)
• PNS pathways can be divided into:
  • Ascending (afferent) pathways: carry sensory information towards CNS
  • Descending (efferent) pathways: carry motor signals away from CNS to innervate effector organs (skeletal, cardiac, smooth muscle, glands, etc.)

Descending (Efferent) Pathways

• Can be divided into:
  • Somatic nervous system: regulates voluntary motor control of skeletal muscle
  • Autonomic nervous system: involuntary control of organ systems/internal viscera, further divided into:
    • Sympathetic nervous system ("fight or flight")
    • Parasympathetic nervous system ("rest and digest")

Cells of the Nervous System

• Neurons:
  • Electrically excitable cells that transmit electrical or chemical information between other neurons to an effector organ
  • Have three main components:
    • Cell body
    • Dendrites
    • Axons
  • Can be classified structurally (unipolar, pseudounipolar, bipolar, multipolar) or functionally (sensory, motor, interneurons)
• Neuroglia (support cells):
  • Provide structural support, nutrition, protection for neurons, and facilitate neurotransmission
  • Types:
    • Oligodendrocytes (CNS): produce myelin
    • Astrocytes (CNS): fill spaces between neurons and surround blood vessels
    • Microglia (CNS): remove debris
    • Ependymal cells (CNS): line CSF-filled cavities
    • Schwann cells (PNS): form myelin
    • Satellite cells (PNS): provide support for neurons

White and Gray Matter

• White matter: myelinated axons organized into tracts
• Gray matter: unmyelinated cell bodies and dendrites, found on the cortical surface and in certain deeper regions

Basal Ganglia and Thalamus

• Basal ganglia:
  • Group of gray matter nuclei deep in the forebrain connected to the cortex, thalamus, and brain stem
  • Control muscle tone, posture, and large muscle movements
  • Include:
    • Caudate nucleus
    • Putamen
    • Globus pallidus
• Thalamus:
  • Relay center for sensory information
  • Associated with sensory input, emotions, memory, and motor planning

Neurotransmitters and Synapses

• Review of action potentials: when a stimulus depolarizes the cellular membrane, triggering a cascade of events that allows the cell to fire
• Chemical synapses:
  • Presynaptic and postsynaptic cells are separated by a thin synaptic cleft
  • Signaling occurs through the release of neurotransmitters from the presynaptic neuron in response to an action potential
  • Neurotransmitters bind to receptors on the postsynaptic membrane, causing a change in the postsynaptic neuron
• Neurotransmitters:
  • Chemical messengers that allow the action potential to cross the synaptic cleft
  • Examples:
    • Acetylcholine
    • Norepinephrine
    • Dopamine
    • Serotonin
    • GABA (gamma-aminobutyric acid)
  • Excitatory vs inhibitory effects on the postsynaptic neuron

Cerebrovascular Disease

• Refers to a group of conditions that affect blood flow and blood vessels in the brain
• Most common is stroke/CVA, which can be ischemic or hemorrhagic

Stroke and Transient Ischemic Attack (TIA)

• Stroke:
  • Abrupt onset of focal or global neurologic impairment
  • Can be ischemic (87%) or hemorrhagic (13%)
  • Types of ischemic strokes:
    • Thrombotic
    • Embolic
    • Lacunar
    • Hypoperfusion
• Transient ischemic attack (TIA):
  • Episode of neurologic dysfunction lasting < 1 hour
  • Due to transient focal cerebral ischemia
  • Causes of TIA:
    • Embolic
    • Lacunar
    • Large artery, low flow

Pathophysiology of Infarction

• Infarction occurs when occlusion leads to loss of blood supply and ischemia, causing cell death
• Infarction leads to necrosis and swelling (cerebral edema) in 48-72 hours
• Ultimately causes disintegration of tissue and glial scarring

Ischemic Core vs Penumbra

• Ischemic core: central area of irreversible ischemia/necrosis
• Penumbra: surrounding area of borderline ischemic tissue that is potentially salvageable
• Restoration of perfusion to the penumbra can prevent necrosis and loss of function

Clinical Correlation: Thrombolytics and Thrombectomy

• Goal in stroke treatment is to intervene early enough to restore perfusion to the penumbra
• Thrombolytics (e.g., tenecteplase) can be used to restore perfusion
• Thrombectomy can be used to physically remove the thrombus in patients who are not candidates for thrombolytics or have a large vessel occlusion### Nerve Repair
• Mature neurons in the CNS (Central Nervous System) have a permanent loss of function after injury, whereas peripheral nerves (PNS) can repair.
• In the CNS, damaged tissue forms a glial scar, restricting future regeneration, whereas in the PNS, Wallerian degeneration occurs, with the distal nerve segment degenerating and the proximal segment growing back.
• The process of nerve repair in the PNS depends on factors such as location, type of injury, degree of inflammatory response, and scar tissue.

Neurons: Axons

• Axons are long projections from the cell body that carry nerve impulses away from the cell body.
• Myelinated neurons have a myelin sheath wrapped around the axon, which is an insulating layer that speeds up transmission.
• Nodes of Ranvier are interruptions in the myelin sheath, allowing for saltatory conduction.

White vs Gray Matter

• White matter is composed of myelinated axons, organized into tracts that bring information to or take it from the cortex.
• Gray matter is composed of unmyelinated cell bodies, found on the cortical surface and doing the work.

Neuroglia (Glial Cells)

• Neuroglia, or "nerve glue," are non-neuron cells that make up the support system of the nervous system.
• Types of neuroglia include:
  • Oligodendrocytes: deposit myelin within the CNS.
  • Astrocytes: fill spaces between neurons and surround blood vessels in the CNS.
  • Microglia: remove debris within the CNS.
  • Ependymal cells: line CSF-filled cavities in the CNS and create CSF.

Demyelinating Diseases

• Diseases can be classified into two types:
  • Leukodystrophies: diseases of myelin formation or maintenance due to intrinsic (genetic) causes.
  • Myelinoclastic: diseases of normally formed myelin caused by extrinsic causes (toxins, chemicals, autoimmune disorders).
• Pathophysiology of demyelinating diseases: loss of the myelin sheath leads to impaired signal conduction, causing progressive neurological dysfunction.

Multiple Sclerosis

• A diffuse, progressive CNS autoimmune disease due to degeneration of CNS myelin, scarring, and loss of axons.
• Onset usually between 20 and 40 years old, more common in genetically female patients.
• Pathophysiology: immune cells (macrophages, T-cells, B-cells) attack myelin, leading to demyelination and axonal loss.
• Clinical manifestations: relapsing-remitting, multifocal symptoms, and lesions on imaging.

Alzheimer's Disease

• A neurodegenerative disease, most common cause of dementia, and one of the leading sources of morbidity and mortality in the aging population.
• Two pathologic hallmarks: extracellular beta-amyloid deposits (plaques) and intracellular neurofibrillary tangles.
• Diagnosis: clinical criteria, including a history of insidious onset and progressive course of cognitive decline, exclusion of other etiologies, and documentation of cognitive impairments.

Meninges, Cerebrospinal Fluid

• The meninges are three layers of protection for the brain: dura mater, arachnoid, and pia mater.
• The subarachnoid space contains CSF, produced by ependymal cells of the choroid plexus.
• CSF has multiple roles, including exerting pressure, providing protection, and transporting hormones and removing waste.

Hydrocephalus

• Accumulation of excess CSF in the ventricular system, either due to overproduction or blockage of CSF flow.
• Types: obstructive, communicating, and normal pressure.
• Treatment: VP shunt, external ventricular drains.

Head Trauma

• Traumatic brain injury (TBI) is an alteration in brain function or other evidence of brain pathology caused by external force.
• Pathophysiology: primary brain injury, including diffuse axonal injury and focal cerebral contusions.
• Mechanisms of injury: direct impact, rapid acceleration/deceleration, penetrating injury, and blast waves.### Intracranial Hemorrhage
• Epidural hematomas, subdural hematomas, or subarachnoid hemorrhage can occur as a result of TBI
• Secondary brain injury occurs due to a cascade of molecular injury mechanisms that start at the time of injury and continue for hours to days
• Mechanisms include free-radical injury to cell membranes, electrolyte imbalances, mitochondrial dysfunction, inflammatory responses, apoptosis, and secondary ischemia from vasospasm
• These mechanisms lead to neuronal cell death and cerebral edema

Concussion

• Mild traumatic brain injury (mTBI) characterized by temporary impairment of neurologic function
• Symptoms include memory loss, attention deficits, headache, and altered mental status
• Neuronal dysfunction occurs due to metabolic insults from the trauma rather than an actual structural abnormality
• Concussed cells become vulnerable, and if a second concussion is sustained during this period, damage can be irreversible
• Hallmark symptoms are confusion and amnesia with or without loss of consciousness

Chronic Traumatic Encephalopathy

• Progressive neurological disorder that often presents like dementia and can also have motor disorders
• Resulting from repetitive closed-head injuries, such as in boxers and football players

CNS Infections

• Meningitis: infection of the meninges resulting in inflammation
• Can be caused by viruses, bacteria, or fungi
• Viral causes include enteroviruses, HSV-1, HSV-2, and VZV
• Fungal causes include cryptococcus and candida, usually seen in immunocompromised patients
• Encephalitis: infection/inflammation of the brain parenchyma itself, not always distinguishable clinically from meningitis

Bacterial Meningitis

• Caused by virulence factors of a pathogen overcoming host defense mechanisms
• Common pathogens include group B streptococcus, Neisseria meningitidis, Streptococcus pneumoniae, H. Influenza, and E. coli
• Invasion of bacteria into the meninges can occur through the bloodstream, direct extension from local infection, or otitis media and sinusitis
• Clinical manifestations include fever, neck stiffness, and altered mental status
• Treatment includes empiric antibiotics and later narrowed based on culture results from CSF analysis

Neurodegenerative & Movement Disorders

• Basal Ganglia:
  • Group of subcortical nuclei responsible for motor control
  • Composed of the substantia nigra, caudate nucleus, and putamen
  • Functions include initiating voluntary motor movement, suppressing unwanted movement, and procedural learning
• Substantia Nigra:
  • "Black Substance" containing high concentration of dopamine (neuromelanin)
  • Most of the dopamine in the brain is located here
  • Neurons project to the striatum, communicating through dopamine signaling
• Indirect & Direct Pathways:
  • Basal ganglia receive information from the cortex and send motor signals back to the cortex through the thalamus
  • Dopamine signaling from the substantia nigra regulates movement through the indirect and direct pathways

Movement Disorders

• Group of neurologic conditions that cause abnormal movements
• Can be either hyperkinetic (increased movements) or hypokinetic (decreased movements)
• Can affect both voluntary and involuntary movements
• Common disorders include ataxia, chorea, dystonia, tremor, Huntington's disease, and Parkinson's disease

Huntington's Disease

• Rare autosomal dominant genetic disorder
• Clinical manifestations include dementia, psychiatric symptoms, and chorea movements
• Progressive and ultimately fatal
• Genetic mutation in the Huntingtin (HTT) gene causes triplet repeat expansion of a particular DNA sequence, leading to neuronal death and dysfunction
• Treatment is focused on symptom management, usually aimed at suppressing chorea movements to improve quality of life

Parkinson's Disease

• Degenerative disorder of the substantia nigra
• Progressive degeneration of dopamine-producing neurons in the substantia nigra
• Symptoms include "pill-rolling" tremor at rest, rigidity, masked facies, shuffling gait, bradykinesia, and dementia
• Clinical correlation: treatment is focused on replacing dopamine in the brain, usually with Levodopa/Carbidopa

Amyotrophic Lateral Sclerosis (ALS)

• Progressive neurodegenerative disorder of upper and lower motor neurons
• Etiology is unknown, with some genetic susceptibility
• Pathophysiology includes motor neuron degeneration and death, cortical motor neuron death, and spinal cord atrophy
• Symptoms include muscle atrophy, weakness, and respiratory failure
• Unfortunately, there is no cure, and the disease is usually fatal within five years of diagnosis

Peripheral Nervous System

• Direct extension of the central nervous system, monitoring and reacting to external stimuli
• Two components: autonomic nervous system (ANS) and somatic nervous system
• ANS helps maintain homeostasis, automatically adjusting the activity of the sympathetic and parasympathetic nervous systems to match the needs of the body
• Somatic nervous system includes afferent (sensory) nerves and efferent (motor) nerves, traveling from the CNS to muscle for motor activation
• PNS is outside of the skull and spinal vertebra, not protected by the blood-brain-barrier, and susceptible to toxic injury from circulating substances

Guillain-Barré Syndrome

• Autoimmune destruction of schwann cells surrounding peripheral nerves
• Post-infectious autoimmune neuropathy, ~70% of patients have a preceding infection
• Campylobacter jejuni is the most common preceding infection, found in undercooked poultry, causing GI illness (diarrhea)
• Molecular mimicry mechanism: campylobacter jejuni membranes have a component similar to ganglioside, a component of peripheral nerves, leading to cross-reaction and attack of peripheral nerves

Clinical Manifestations of Guillain-Barré Syndrome

• Symmetric, ascending weakness is the hallmark, typically begins in the legs
• Numbness, tingling, and weakness that can progress to paralysis
• Symptoms generally progress over a period of 2 weeks

Diagnosis and Treatment of Guillain-Barré Syndrome

• Clinical diagnosis, typically based on preceding infection and characteristic presentation
• EMG and nerve studies can be helpful if unclear
• Supportive care, monitor for progression, respiratory status, and blood pressure
• Main medication: IVIG (intravenous immunoglobulin), with specific criteria for use

Carpal Tunnel Syndrome

• Common condition causing numbness, tingling, and pain in the hand and forearm
• Anatomic issue: compression of the median nerve as it travels through the wrist (carpal tunnel)
• Presents as pain, paresthesia, and less commonly, weakness in the median nerve distribution
• Congenital predisposition: some people have smaller carpal tunnels than others

Charcot-Marie-Tooth Disease (CMT)

• Group of hereditary disorders causing peripheral neuropathy in both sensory and motor neurons
• Abnormalities in axons or production/maintenance of the myelin sheath
• Demyelinating disorder of the peripheral nervous system
• Symptoms typically begin in the feet/lower legs and then the fingers, hands, and arms
• High arched feet due to muscular imbalance (from atrophy)

Pathophysiology of Charcot-Marie-Tooth Disease

• Pathogenic variants in genes that make proteins for peripheral nerve and myelin sheath maintenance
• Abnormalities in peripheral nerves or myelin, leading to thin or misfolded myelin sheaths, alternating segments of demyelination, and axonal loss

Myasthenia Gravis

• Autoimmune disorder of the neuromuscular junction, manifesting as progressive skeletal muscle weakness and fatigability
• Pathogenesis: autoantibodies to the acetylcholine receptor, binding to the receptor and interfering with neurotransmitter function
• Clinical manifestations: generalized proximal limb weakness and fatigability, drooping of eyelids (ptosis), double vision (diplopia), flattened smile, and difficulty chewing and/or swallowing

Treatment of Myasthenia Gravis

• Acetylcholinesterase inhibitors to block the enzyme that breaks down Ach
• Immunosuppressants like corticosteroids
• Plasmapheresis to remove autoantibodies from the blood
• IV immunoglobulin to give other antibodies that block the anti-AChR antibodies