Unformatted text preview: Pathophysiology Study guide for Nervous system
Brief review anatomy and physiology
The nervous system is divided into the
1. Central nervous system
III. Forebrain – Cerebral hemispheres (frontal, parietal, temporal and occipital) basal
ganglia, diencephalon (thalamus and hypothalamus)
Midbrain – the cerebral aqueduct connecting third and fourth ventricle,
corticospinal tracts. CN III and IV arise from mid brain
Hindbrain – medulla oblongata, pons and the cerebellum – CN V – XII arise from
hind brain b) Spinal cord
The brain stem – includes medulla, pons and midbrain
2. Peripheral nervous system
a) Cranial nerves originating from the brain ( 12 cranial nerves)
b) Spinal nerves originating from the spinal cord ( 31 pairs spinal nerves – 8 cervical, 12
thoracic, 5 lumbar, 5 sacral and 1 coccygeal
The nervous system has two types of cells – the neurons and the neuroglial cells.
The functional cells of the nervous system are called the neurons. The afferent (sensory) neurons
transmit information to the central nervous system and the efferent (motor) neurons transmit
information from the central nervous system.
The neuron has three parts
a) Dendrites – main source of information for the neuron – they conduct information towards the
b) Cell body – controls cells activity
c) Axon – conducts impulses from the cell body to the synapse.
The neuroglial cells provide protection and regulate blood flow to the neurons – production of myelin
which provides insulation helps in increasing speed of the impulses.
The brain receives 15-20% of the cardiac output. Neurons cannot store glucose therefore decreased
blood sugar can result in signs of neural function disruption – unconsciousness.
Neurons communicate through electrical signals called action potentials.
Synapses are structures through which neurons communicate. There are two types of synapses electrical and chemical synapses. Electrical synapses allow action potentials to move from one cell to another.
Chemical synapses depend on chemical messengers known as neurotransmitters, that are released from
the presynaptic neuron, released into the synaptic cleft and then interact with receptors on the post
Neurotransmitters are the chemical substances that control neural function – they inhibit, excite or
modify. Examples of neurotransmitters are
IX. GABA (gamma aminobutyric acid)
Dopamine The action of the neurotransmitter depends upon the receptor – whether it is excitatory or inhibitory.
The layers of the meninges – dura mater, arachnoid and pia mater.
CSF is produced by the ependymal cells in the ventricles and reabsorbed into the venous system through
the arachnoid villi.
The blood brain barrier and the CSF brain barrier maintain a stable chemical environment in the brain.
The blood brain barrier – is attributed to the uniqueness of the brain capillaries – endothelial cells of the
brain capillaries are joined by continuous tight junctions and most capillaries are surrounded by
basement membrane and astrocytes. Large molecules such as proteins are prevented from crossing the
blood brain barrier. Water soluble medications cannot cross the barrier, but lipid soluble medications are
able to cross the lipid layer. Alcohol, heroin and nicotine are lipid soluble and cross the blood brain
The autonomic nervous system (ANS) – is responsible for maintaining vital visceral functions of the
body such as blood pressure, blood flow, respiration, body temperature, digestion, metabolism and
elimination. It is influenced by emotions. Blushing, pallor, palpitations, clammy hands and dry mouth are
mediated through the ANS.
The ANS has two divisions
I. Sympathetic nervous system – responsible for the fight or flight reaction – heart rate accelerates,
blood pressure rises, blood flows from the skin and GI tract to the muscles and brain, blood
sugar increases, bronchioles and pupils dilate, sphincters of the stomach and intestine and the
internal sphincter of the urethra constrict. II. Parasympathetic nervous system – it is known as the rest-digest response. It slows the heart
rate, stimulates gastrointestinal function, promotes bowel and bladder elimination, constricts
the pupil The neurotransmitters for the ANS are acetylcholine and catecholamines – epinephrine and
Pain is an “unpleasant sensory and emotional experience associated with actual and potential tissue
damage” (International Association for the Study of Pain)
Origin of pain can be
II. Nociceptive – nociceptive receptors are free nerve endings which are activated in response to
actual or potential peripheral tissue damage.
Neuropathic – Direct injury or dysfunction of the sensory axons of the peripheral or central
nerves Pain is classified based on duration
I. II. Acute – less than 6 months, usually presence of autonomic nervous system - sympathetic
response (tachycardia, blood pressure, dry mouth, muscle tension, decreased gut motility),
associated with anxiety
Chronic – greater than 6 months – absence of autonomic response, other responses are
depression, insomnia, decreased libido, decreased strength of relationships. Chronic pain is
leading cause of disability. Pain is classified based on location
II. Cutaneous and deep somatic pain – superficial structures – sharp or burning pain, localized.
Deep somatic pain – muscles, joints, tendons, blood vessels. Diffuse pain.
Visceral – strong contractions, distension and ischemia can cause affect the walls of the viscera
causing severe pain. Pain is classified on site of referral
Referred pain is felt at a site different from point of origin but innervated by same spinal segment. Pain
from thoracic and abdominal viscera is diffuse and poorly localized. Eg. Myocardial infarction – can be
felt in the left arm, neck, chest.
Neuropathic pain - caused by injury to peripheral nerves in a single area – nerve entrapment or
compression from tumor. Or caused by damage to peripheral nerves in a wide area such as in diabetes
Trigeminal Neuralgia – severe, brief repetitive, stabbing pain without numbness that occurs along
distribution of cranial nerve V, possible cause being result of demyelination. Post herpetic neuralgia – It occurs after infection with shingles. it can present as constant burning,
aching or throbbing pain or intermittent stabbing or shooting pain or stimulus evoked pain, occurs over
affected dermatome. During infection with shingles nerve fibers from the skin to the spinal cord are
Phantom limb pain – pain that occurs after amputation of limb or part of limb. Starts as tingling,
squeezing and heaviness and later becomes burning, cramping or shooting pain. Different theories of
cause of phantom pain – the end or the regenerating axon is trapped in the amputated site/spontaneous
firing of the neurons of the spinal cord that have lost their usual sensory input/or changes in the flow of
the signals through the somatosensory areas of the brain HEADACHES
According International Headache Society – headaches are classified as
III. Primary headache – migraine, cluster headache, tension-type headache
Headache secondary to other medical conditions – meningitis, brain tumors, cerebral aneurysm,
traumatic brain injury
Cranial neuralgias and facial pain – TMJ RED FLAGS sudden onset severe, intractable headache in an otherwise healthy person –
subarachnoid hemorrhage or meningitis
change in pattern or progression of headache or new headache in people older than
also change in pattern or progression of headache in people with cancer,
immunosuppression or pregnancy Migraine
I. II. migraine with aura – aura may occur 5- 20 minutes before and last for about 5 minutes
to an hour – aura may include loss of vision, numbness, speech disturbances, feeling
pins and needles
migraine without aura – pulsatile, throbbing, unilateral headache , lasts 1-2 days,
aggravated by routine physical activity , associated with nausea and vomiting and
increased sensitivity to light and sound, visual hallucinations such as stars, sparks and
flashes of light Pathophysiology is not well understood - few theories – stimulation of the trigeminal sensory fibers lead
to release of neuropeptides causing neurogenic inflammation within meningeal vasculature – neurogenic
vasodilation of meningeal blood vessels.
Precipitating factors of migraines menstrual periods, dietary items such as monosodium glutamate, aged
cheese and chocolate. Cluster headache
Rapid onset and reaches peak in 10-15 minutes lasting 15-180 minutes. Pain can occur behind one eye
radiating to the trigeminal nerve on the same side. Headache is associated with restlessness, agitation,
conjunctival redness, lacrimination and constriction of pupil in affected eye, nasal congestion, forehead
and facial swelling, ptosis and edema of eyelid.
Occurs in men more than women. Occurs around third decade. Occurs in clusters over weeks or months
followed by long remission.
Primary neurovascular headache that causes this severe unilateral pain. Tension headache – most common type of headache
Dull, aching, diffuse headaches that occurs in a hatband distribution around head, not associated with
nausea or vomiting or affected by activity.
May be caused by psychogenic stress, anxiety, depression or muscular stress, overuse of analgesics or
caffeine. Coordination of movement depends upon
IV. Motor system for muscle strength
Cerebellar system for rhythmic movement and steady posture
Vestibular system for posture and balance
Sensory system for position sense Ataxia – wide based unsteady gait
Dysmetria – if the person is unable to touch examiners finger and then touch his/her own finger
Bradykinesia – slowness of movement
Myoclonus – involuntary jerky movements
Chorea – abnormal writhing movements
Motor unit - Motor neuron and group of muscles innervated by the motor neuron.
Lower motor neuron (LMN) - Motor neuron supplying a motor unit is located in the ventral horn of the
Upper motor neuron (UMN) – they arise from the cerebral cortex to the ventral horn. The UMON exerts
control over the LMN.
Paralysis – loss of muscle movement
Paresis – weakness of muscle movement Myasthenia gravis – Autoimmune disease caused by antibody mediated loss of acetylcholine receptors
in the neuromuscular junction, which results in alteration of neuromuscular signal transmission. Result is
muscle weakness and fatigability. Seen more in women than men. Associated with Epstein-Barr virus.
70% of people with myasthenia gravis have tumors of the thymus or thymic hyperplasia.
Clinical manifestations. - ptosis (weakness of eyelid), diplopia (weakness of extra ocular muscles) ,
difficulty chewing and swallowing, proximal limb weakness, symptoms less pronounced upon awakening
and then gets worse as the day goes by.
Myasthenic crisis – sudden exacerbation of symptoms, with compromise to ventilation requiring
ventilator support and airway protection. Crisis can be precipitated by infection, emotional upset,
pregnancy, ingestion of alcohol, exposure to cold or surgery.
Diagnosis is made from history and physical, anticholinesterase test, EMG (electromyography), check for
acetylcholine receptor antibodies. Treatment includes immunosuppression, corticosteroids, thymectomy,
plasmapheresis (remove antibodies from circulation)
Carpal tunnel syndrome – caused by compression of the median nerve. Predisposing conditions that
reduce size of the carpal tunnel – such as bony or ligament changes. Also by increase in volume of tunnel
contents such as inflammation of tendons, synovial swelling or tumors. Most common cause is repetitive
use of wrist.
Clinical manifestations are pain, numbness and tingling of the thumb and first two and one half digits of
the hand. Pain in the wrist and hand that is worse at night, weakness of precision grip and atrophy of
abductor pollicis muscle.
Diagnostic procedures – Tinel sign – light percussion over the median nerve at the wrist causes tingling
sensation radiating into the palm of the hand. Phalen maneuver – the wrist is held in complete flexion
for one minute, numbness and tingling along the median nerve or increased symptoms area positive
sign for carpal tunnel syndrome.
Guillain-Barre syndrome – rapidly progressive ascending symmetrical limb weakness and loss of tendon
reflexes – resulting in acute flaccid non traumatic paralysis. Majority of people had an influenza like
illness before onset of symptoms. There is infiltration of mononuclear cells around capillaries of the
peripheral neurons, demyelination of the ventral spinal roots and edema of the endoneurial
compartment (connective tissue around myelin)
Paralysis may extend to the respiratory muscles requiring mechanical ventilation . autonomic nervous
system functions are affected causing postural hypotension, arrhythmias, facial flushing, urinary
retention and profuse sweating (hyperhidrosis)
Disc herniation – causes are trauma, aging and degenerative disorders of the spine. Most lumbar
herniation occur in the L4 or L5 to S1. Most cervical herniation are from C5-C6 and C6 to C7.
Pain in the back radiating down the leg and over sole of feet, pain is aggravated by coughing, sneezing,
straining, stooping, standing. Some motor weakness. Numbness and paresthesia of the leg and foot.
Diagnostic maneuver is straight leg test – with the person in the supine position, passively raise the leg.
Pain in the hamstring muscle when raising leg to sixty degrees or less is a positive test. RED FLAGS for BACK PAIN
Gradual onset of pain (may indicate malignancy or infection)
Younger than 20 years (congenital or developmental disorders) or older than 50 years (aortic aneurysm,
malignancy, compression fracture)
Pain that worsens when laying down may indicate malignancy or infection
Thoracic back pain – (recent MVA or fall or possible tumor)
History of trauma, night sweats, immunosuppression, malignancy
Unintentional weight loss
Associated with urinary and fecal incontinence, gait abnormalities, paresthesias, weakness may indicate
spinal cord compression Parkinson disease - It is a degenerative disorder affecting the basal ganglia, there is destruction of the
nigrostriatal pathway which leads to reduced concentration of dopamine. It believed to be caused as a
result of genetic predisposition and exposure to environmental factors.
Parkinsonism- is a clinical syndrome – can result from side effects of antipsychotic drugs that block
dopamine receptors, severe carbon monoxide poisoning, toxic reaction to a chemical, post encephalitis,
post CVA, brain tumors, repeated head trauma and other degenerative neurological disorders.
The cardinal clinical manifestations are tremor, rigidity and bradykinesia
Tremor – alternating flexion and contraction movements, rhythmic, usually unilateral (later progresses to
bilaterally), occurs when limb is supported and at rest, disappears with movement and sleep, affects
distal segments of limbs (hand and feet), head, neck, face, lips and tongue. “rolling a pill between thumb
Rigidity – resistance to movement of both flexors and extensors throughout full range of motion, initially
unilaterally and then progresses to bilateral sides. Flexion contractions may result.
Bradykinesia – slow to initiate or perform movements and difficulty with sudden cessation, unexpected
stopping of voluntary movements. They have difficulty initiating walking, turning, they lean forward
when walking, and take small shuffling steps, sometimes they freeze in a position as if their feet are
glued to the ground. Facial expressions become masklike, loss of blinking reflex, difficulty swallowing
saliva – drool. Speech becomes slow and monotonous.
As the basal ganglia also affects the autonomic nervous system - They may also have excessive and
uncontrolled sweating and salivation. Increased tearing, dysphagia, orthostatic hypotension,
constipation, impotence and urinary incontinence may occur.
Cognitive dysfunction also occurs – decline in executive functioning – difficulty planning, starting and
carrying out tasks. Treatment is with medications that increase dopamine levels, stimulate dopamine receptors and prevent
breakdown of dopamine and also with use of anticholinergics. Other treatment is with DBS (deep brain
Multiple sclerosis –
It is an immune mediated disorder in genetically predisposed individuals, that causes inflammation and
destruction of the myelin in usually the white matter of the CNS. affects the optic nerves,
periventricular white matter, brain stem, cerebellum, and white matter of the spinal cord.
Age of onset is between 20-30 years, affecting women twice the number of men.
Clinical manifestations – paresthesias over face or extremities, optic neuritis (clouding of vision, partial
loss of vision, visual field defect, pain with movement of globe of eye), diplopia, abnormal gait, bladder
and sexual dysfunction, vertigo, fatigue and speech disturbances. Symptoms may last for days and weeks
and then spontaneously resolve. After a period without symptoms, patients may present with new
symptoms. Depression, euphoria, inattentiveness, apathy, forgetfulness and memory loss may be
present. Fatigue is a predominant symptom.
Cerebrovascular Accident/brain attack/Stroke
Two main types of stroke
II. Ischemic – interruption in blood flow in a cerebral vessel. 87% of all strokes
Hemorrhagic – 13% of all strokes. Intracerebral (10%) and subarachnoid (3%)
hemorrhage is usually related to rupture of blood vessel as a result of hypertension,
aneurysm, arteriovenous malformations. Higher mortality rate. Stroke risk factors
III. Non modifiable – age (increase with age), gender (at younger age men have higher incidence,
however since women live longer, more women die of stroke), race, prior stroke, family history
Modifiable – hypertension, hypercholesterolemia, diabetes mellitus, hyper coagulopathy, cardiac
disease (atrial fibrillation, rheumatic heart disease, myocardial infarction, bacterial endocarditis)
Modifiable behavioral – cigarette smoking, alcohol, birth control pills in combination with
smoking, physical inactivity, obesity, use of illicit drugs – cocaine, amphetamines and heroin.
Cocaine associated with hemorrhagic stroke. Stroke risk calculation for patients presenting with non valvular atrial fibrillation
CHA2DS2VASc score – C – heart failure – 1 point , H – hypertension – 1 point, A-age greater and equal to
75 years (gets 2 points) , D- diabetes mellitus – 1 point, S – prior history of stroke – 2 points, V-vascular
disease (aortic plaque, peripheral artery disease, prior myocardial infarction) -1 point, A-age 65-74 years,
Sc –gender –women get one point.
The decision is made to anticoagulate if risk score is 2 and greater than 2. TIA (transient ischemic attack) a transient obstruction of cerebral blood flow which resolves before
infarction. After a TIA - 10-15% have CVA within 3 months. 50% in first 48 hours. Clinical manifestations of stroke depend on are of infarction in the brain. Facial droop, arm weakness,
and slurred speech. If the cortex is affected – aphasia or neglect, visual field defects, amaurosis fugax
(transient monocular blindness), moto hemiplegia, sensory hemiplegia, dysarthria, aphasia. If the
ischemia is in the vertebrobasilar segment results in diplopia, ataxia, vertigo, ataxia, hemianopia.
Subarachnoid hemorrhage – may have atypical headaches days or weeks before hemorrhage possibly
from small leak. Subarachnoid rupture results in “worst headache of my life” “thunderclap”may be
associated with collapse, vomiting, nuchal rigidity (neck stiffness), photophobia (intolerance to light),
diplopia, blurred vision.
Complications of subarachnoid hemorrhage are – rebleeding, vasospasm, cerebral ischemia,
hydrocephalus, hypothalamic dysfunction and seizu...
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