Pathophysiology of Neurological System

motor unit is made of

peripheral motor neuron (PMN) and the m fibers it innervates

innervation ratio determines what

precision with which the m is controlled

Axonal degeneration

axon + myelin shear degenerate, atrophy of myocytes

Reinneervation

sprouting of adjacent motor axons leads to myocyte type grouping

Myopathy

scattered myocytes of diff motor units degenerate

Somatic sensory function depends on

distal n endings, axon connecting to the dorsal root ganglia, proximal axon synapsing on spinal cord

what do peripheral nerves consist of

multiple fibers grouped into fascicles by connective tissue sheaths

myelinated fibers are sheathed by _________ and are separated by _______-

Schwann cells

nodes of Ranvier

Polyradiculonevritis

multiple spinal roots inflamed w/ damage to peripheral n proximal segments, caused by immune mediated process after infection

Guillain-Barre Syndrome (GBS) + Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

autoimmune polyradiculoneuropathies w/ widespread peripheral nerve involvement

commonality and difference bw GBS and CIDP

motor dysfxn affecting limbs

GBS has faster and shorter onset

immune attack in guillain-barre

myelin from peripheral nerves targeted by nervous drive block and motor deficit, action potential blocked/conduction failure occurs secondarily

signs and symptoms of guillain-barre

motor deficit w/ ascending sensory deficits, gait ataxia, resp + ANS dysfxn

neurologic findings in guillain-barre

symmetrical weakness

what cells are effector cells that damage myelin and axons in GBS and CIDP

lymphocytes and macrophages

molecular mimicry of Guillain-Barre (+CIDP)

immune system attacks host tissue w/ homologous epitopes after infection

Campylobacter jejuni in CIDP + AMAN of GBS

antibodies are against gangliosides

in AIDP, APCs present to T cells which activate ________

endoneurial macrophages

T and B cell role in aidp

T cells help B cells transform into plasma cells - produce antibodies that cross BNB and bind to + dissolve myelin

AMAN subtype of GBS

IgG deposits and complement in axolemma of motor n at Ranvier nodes + sodium channel dysfxn, by antibodies against GM1 and GD1

risk factors in GBS vs Myasthenia Gravis

GBS - males

MG - young females

Immune attack in AIDP

against Schwann cells at peripheral nerve roots with IgG and complement

the following clinical features describe which pathology: after C. jejuni, rapid motor deficiency, long recovery

AMSAN

immune attack of AMSAN

against axon at ranvier nodules (Wallerian degeneration)

Miller Fisher syndrome (of GBS)

ocular m palsies + ataxia present, w/ IgG against gangliosides

__________ is a chronic form of polyradiculoneuritis

CIDP

where are clinical features in CIDP

proximal weakness in all limbs

therapeutic indications for GBS + CIDP

IgG iv, plasmapheresis, corticosteroids

2 major functional elements (by Schwann cells) of peripheral n

axonal processes and their myelin sheaths

epineurium, perineurium, endoneurium

connective tissue layers of nerve

blood-nerve barrier

epitheloid cells line inner surface which joins occluding zones

Wallerian degeneration

swelling and fragmentation of distal axon + branches, detritus digested by Schwann cells + macrophages

Demyelination

segmental destruction of myelin sheath without axonal loss, lesions of Schwann cells

Neurapraxia

injury by conduction block, from contusion -> ischemia

Axonotmesis

damage to axons w/ Wallerian degeneration

Tinel's sign

tingling on light percussion over regenerating segment, present in axonotmesis

Neurotmesis

complete division of peripheral nerve, axon divides w/ Wallerian degeneration, regenerate w/o myelin, recovery incomplete

neuroma

lack of myelin sheath guide during regeneration of nerve, tangled mass of Schwann cells and fibroblasts

PMN axon reaches m where it splits into terminations, forming

neuromuscular jxn

postsynaptic membrane has

nAchR and AchE

AchE function

hydrolyzes Ach released into synaptic clef in choline and acetate, choline shipped to motor axon

Postsynaptic pathology of neuromuscular junctions

Myasthenia gravis

Myasthenia gravis

autoantibodies against postsynpatic NMJ (Ach receptors) - muscle weakness

Cause of MG

development of autoantibodies directed at nicotinic AChR (postsynaptic membrane)

thymic hyperplasia in which patho

MG (T cells generated by it)

Presynaptic pathology of neuromuscular junctions

Eaton-Lambert's syndrome

Eaton-Lambert's syndrome

auto atb against ca+ voltage dependent channels, triggering Ach-exocytosis and Ach release reduction, motor and sensory dysfxn

paraneoplasmic syndrome associated w/ eaton lambert

LEMS

small cell lung cancer

In Eaton-Lambert, neuromuscular jxn activity may be affected by ______ by _________

toxins (botulinum), preventing release of acetylcholine

stroke is the result of

ischemia or hemorrhage of cerebrum

anterior cerebral circulation is supplied by

carotid arteries (ACA and MCA)

posterior cerebral circulation is supplied by

basilar artery

classification of strokes

ischemic (thrombotic and embolic) and hemorrhagic (intracerebral and subarachnoid)

ischemic stroke

inadequate cerebral blood flow from arterial obstruction

Thrombotic stroke

obstructed lumen then infarction by atherosclerosis, causes thrombus and emboli

Lacunar stroke

cavity where infarcted tissue is, w/ neuro deficits

Embolic stroke

embolus reaches a cerebral artery and cause occlusion - infarction + edema occurs, sudden + severe

hemorrhagic strokes occur due to

bleeding inside brain tissue from vessel's rupture

subarachnoid hemorrhagic strokes are caused by

aneurysmal rupture

aneurysm

ballooning of a weakened portion of an arterial wall

3 metabolic factors that affect cerebral blood flow

- co2 increase

- h+ increase

(vasodilation)

- o2 decrease

sympathetic nervous system in cerebral blood flow regulation

vasoconstricts if high bp, vasospasm in lesions

cerebrovascular events

lesions of brain induced by decreased O2 and glucose from vessel lesions

cerebral ischemia

reduction in brain blood flow, causing ischemia and neurotoxicity

size of cerebral ischemia depends on

tonus of collateral network, blood viscosity and perfusion p

collateral system in cerebral ischemia

anastamoses bw carotid and vertebral a

hemodynamic theory of stroke

decrease in systemic bp - decreased flow thru collaterals - narrowing of extracerebral a

border infarctions

resulting lesions of border areas bw regions irrigated by different main cerebral a, in cerebral ischemia

low protein synthesis and glucose use, anaerobic glycolysis initiated and ionic transport damaged is a result of what

cerebral ischemia

in acute cerebral ischemia, __________ leads to __________ due to cessation of oxidative phosphorylation in mitochondria, leading to _________ build up

perfusion failure

energy failure

acidosis

oxidative stress is the result of what in the ischemic cascade

acidosis which develops from lactate producing in anaerobic glycolysis

In ischemic cascade, as atp supply falls, _________ fails

sodium pump

Excitotoxicity in ischemic cascade

firising thresholds of depolarized neurons release high amounts of neurotransmitters (glutamate), which further depolarizes cell - ca+ influx

how does elevation in intracell Ca+ induce cell death

activates harmful enzymes

cerebral infarction is composed of

ischemic + necrotic core and surrounding ischemic penumbra

treatment to injury states related to cerebral blood flow are directed at

maintaining cerebral perfusion p and controlling intracranial p

2 types of cerebral edema

vasogenic and cytotoxic

effects of cerebral edema are caused by

the distortion of blood vessels, the displacement of brain tissues, increased ICP and brain tissue herniation

vasogenic edema is caused by

increased permeability of capillaries that form bbb, drawing water to mostly white matter

vasogenic edema resolves by

slow diffusion

cytotoxic edema

toxic factors affect cells of parenchyma, causing failure in active transport (intracell edema, no bbb disruption)

cytotoxic edema is caused by

ischemia/hypoxia

cytotoxic edema occurs in

gray matter

ischemic cerebral edema

abnormal accumulation of fluid in parenchyma w/ increase in v

cellular edema has 2 phases

1. cytotoxic, in gray matter

2. vasogenic, in white matter

_________ compressions nervous tracts' neurons and vascular structures - cell lesions

vasogenic edema

receptive field

the region of the sensory surface that, when stimulated, causes a change in the firing rate of that neuron

cells of receptive field

on center - stimulation of inner zone increases n firing

off center - opposite

dorsal column-medial lemniscal pathway

an ascending somatic sensory pathway that mediates information about touch, pressure, vibration, and limb proprioception,oflimbs