Download Musculoskeletal and Nervous System Review

Musculoskeletal and Nervous
System Review
Felix Hernandez, M.D.
Muscle Tissue
Skeletal Muscle
Cardiac Muscle
Smooth Muscle
Skeletal Muscle
Long cylindrical cells
Many nuclei per cell
Striated
Voluntary
Rapid contractions
Cardiac Muscle
Branching cells
One or two nuclei per cell
Striated
Involuntary
Medium speed contractions
Smooth Muscle
Fusiform cells
One nucleus per cell
Nonstriated
Involuntary
Slow, wave-like contractions
Microanatomy of Skeletal Muscle
Acetylcholine Opens Na+ Channel
Muscle Contraction Summary
Nerve impulse reaches myoneural junction
Acetylcholine is released from motor neuron
Ach binds with receptors in the muscle
membrane to allow sodium to enter
Sodium influx will generate an action potential
in the sarcolemma
Muscle Contraction Continued
Action potential travels down T tubule
Sarcoplasmic reticulum releases calcium
Calcium binds with troponin to move the
troponin, tropomyosin complex
Binding sites in the actin filament are
exposed
Muscle Contraction Continued
Myosin head attach to binding sites and create
a power stroke
ATP detaches myosin heads and energizes
them for another contraction
When action potentials cease the muscle stop
contracting
Isometric Contraction
Produces no movement
Used in
Standing
Sitting
Posture
Isotonic Contraction
Produces movement
Used in
Walking
Moving any part of the body
Neurogenic Atrophy
•
Transection of the larger
nerves can be repaired if
the proximal part of the
axon is preserved.
•
The nerve distal to the
transection injury
degenerates (wallerian
degeneration).
•
Fiber type grouping is seen.
Figure 20-06
Myasthenia Gravis
•
Autoimmune disease involving the
neuromuscular junction (NMJ)
•
More common in women than in men
•
Cause unknown
•
In the younger age group, associated with
enlargement of the thymus
–
•
Hyperplasia or neoplasia (thymoma)
Striated muscles histologically normal
Myasthenia Gravis
Figure 20-07
Myasthenia Gravis
•
Reduced number of surface receptor sites for
acetylcholine at the motor neural plate
•
Easy fatigability and muscular weakness
•
Small extraoccular muscles and facial muscles
most often involved
•
Ptosis, diplopia, easy fatigability on reading,
facial muscle weakness, inability to chew; all
muscles may become affected
Muscular Dystrophies
•
Genetic defects inherited as mendelian traits
•
Primary muscle cell pathology
•
A progressive course and symptoms related to
muscle wasting
Duchenne-type Muscular Dystrophy
•
Most common muscular
dystrophy
•
Caused by deficiency of
dystrophin
•
Dystrophin holds
together other structural
proteins, linking them to
the cell membrane
Figure 20-08
Duchenne-type Muscular Dystrophy
•
Degeneration of skeletal muscle cells with
ensuing muscle weakness
•
Sex-linked recessive disease
•
Occurs only in boys
•
Mothers asymptomatic
•
Milder form—Becker’s dystrophy
Duchenne-type Muscular Dystrophy
•
In the early stages, individual muscle cell degeneration
and loss occur.
•
The abnormal muscle cells have an irregular shape,
granularity of cytoplasm, and centrally located nuclei.
•
Muscle cell loss is progressive.
•
Compensatory hypertrophy of viable fibers occurs.
•
There is ingrowth of fibrous tissue and fat cells.
Duchenne-type Muscular Dystrophy
•
Appearance of symptoms in preschool children
•
Weakness of the weight-carrying muscles of the pelvic
girdle and lower extremities
•
Difficulty getting up from a squatting position
•
Deformed legs, inability to keep legs straight,
contractures and deformities of the extremities
•
Pulmonary infections, heart failure, anemia, reduced
intelligence
•
Early death—usually in late teens or early 20s
Tumors of Muscles and Soft Tissues
•
Rhabdomyosarcoma
•
Synovial sarcoma
•
Liposarcoma
•
Leiomyosarcoma
•
Angiosarcoma
Functions of Skeletal System
•
SUPPORT: Hard framework that supports and anchors the soft
organs of the body.
•
PROTECTION: Surrounds organs such as the brain and spinal
cord.
•
MOVEMENT: Allows for muscle attachment therefore the bones are
used as levers.
•
STORAGE: Minerals and lipids are stored within bone material.
•
BLOOD CELL FORMATION: The bone marrow is responsible for
blood cell production.
Features of a Long Bone:
Epiphysis: Ends of the
bone.
Diaphysis: The shaft of the
bone which surrounds the
medullary cavity.
Articular Cartilage:
Cushions the ends of the
bones and allows for
smooth movement.
Epiphyseal Plate:
Areas made of cartilage
allowing for the growth of
the bone.
Bone Structure
•
Periosteum – hard outer covering
Cells for growth and repair
•
Compact bone – hard strong layer
Bone cells, blood vessels, protein with Ca and P
•
Spongy bone – at ends of long bones
Has small open spaces to lighten weight
Marrow cavity – hollow in middle of long bones
Bone Marrow
Red marrow – produces blood cells and clotting factors
Found in humerus, femur, sternum, ribs, vertebrae,
pelvis
Produces RBC 2 million per second
Yellow marrow – stores fat
Found in many bones
Bone Structure
Haversian System
Structure of compact bone
Rings of bone tissue with blood vessels and
nerves in the center
Bone Development
Initial skeleton of cartilage in infants
Replaced with bone by osteoblasts
More than 300 bones at birth – fuse to 206
Always growing and breaking down
Osteoblasts – form new bone cells
Osteoclasts – break bone cells down
Osteoporosis
•
Multifactorial disease characterized by
absolute reduction of the total bone mass
•
Age related—in those older than 85 years, one
third have osteoporosis
•
Women > men, especially after menopause
•
Etiologically subdivided into two groups:
–
Primary osteoporosis—cause unknown
–
Secondary—related to another disease
Pathogenesis of Primary Osteoporosis
•
Etiology unknown, but certain factors are
known to predispose to osteoporosis
•
Low initial bone mass (“small frame”)
•
Bad dietary habits, smoking
•
Hormones (e.g., early menopause)
•
Age-related changes in the metabolism
Causes of Secondary Osteoporosis
•
Hormonal disturbances—excess of cortisol,
deficiency of sex hormones
•
Dietary disorders—vitamin C or calcium deficiency,
malabsorption of food
•
Immobilization
•
Drugs—anticonvulsants, anticoagulants (e.g.,
heparin)
•
Tumors—breast cancer
Osteomalacia
•
Softening of bones as a result of inadequate
mineralization of the organic matrix (osteoid)
•
Caused by deficiency of vitamin D, inadequate
metabolic processing and activation of vitamin
D, or disturbances of phosphate metabolism
Etiology of Vitamin D Deficiency
•
Inadequate intake—malnourished children in
Africa, food faddists in United States
•
Inadequate exposure to sunlight—people living
above the Arctic Circle
•
Abnormal intestinal absorption
Pathology of Osteomalacia
•
Excess nonmineralized osteoid
•
Bone deformities and fractures
•
Rickets = osteomalacia in children
–
–
Bowlegs
Widened costochondral junction (“rachitic
rosary”)
–
Craniotabes
–
Delayed dentition
Paget’s Disease
•
Common chronic disease of unknown etiology
characterized by irregular restructuring of bone
and subsequent thickening and deformities of
bones
•
Diagnosis made radiologically
•
Three phases
–
Destructive phase
–
Mixed phase
–
Osteosclerotic phase
Paget’s Disease
•
(1) In the first stage, there is irregular
osteoclastic resorption of bone;
•
(2) In the second stage, osteoblasts react by
actively laying down new bone, which balances
the osteolysis and maintains the total bone
volume. The disease can be recognized at this
stage by the irregular manner in which
osteoblasts lay down trabeculae. The new bone
is highly vascular;
•
(3) Finally, there is a sclerotic phase in which
osteoblastic activity is greatly in excess of
osteoclastic resorption, leading to marked
thickening of bony trabeculae and cortex
Paget’s Disease
Figure 19-07A
Fractures
Figure 19-08
Bone Tumor
• Malignant tumors
•
Benign tumors
–
Osteoma
–
Chondroma
–
Fibroma
–
Giant cell tumor
(benign in most
cases but may
recur)
– Osteosarcoma
– Chondrosarcoma
– Ewing’s sarcoma
Osteoarthritis—Degenerative Joint Disease
(DJD)
•
Most common joint disease
•
Disease of old age
•
Affects weight-bearing big joints but also
small joints of hands and feet
•
Classified as:
–
Primary—cause unknown or multifactorial
–
Secondary—related to another disease
Osteoarthritis
Figure 19-14
Osteoarthritis
•
Crepitus is a characteristic feature—a grating
sound produced by friction between adjacent
areas of exposed subchondral bone.
•
Osteophytes may be visible clinically—as bony
masses such as those that occur over affected
distal interphalangeal joints (Heberden's nodes)
Rheumatoid Arthritis
•
Chronic systemic disease of unknown etiology
characterized by the following:
–
Chronic, symmetric inflammation of joints
•
proximal interphalangeal joints
•
Involved joints are swollen, painful, and stiff.
Stiffness is maximal in the morning after the joint
has been inactive during the night
–
Significant, but not diagnostic, laboratory findings
indicative of immune disorder
–
Variable extra-articular findings
Rheumatoid Arthritis
Figure 19-15
Rheumatoid Arthritis—Clinical Features
Figure 19-16
Gout
•
Common systemic metabolic disorder often
affecting the joints
•
Hyperuricemia—deposition of urate crystals in
tissues; inflammation of joints
•
Podagra (swelling and pain of first
metatarsophalangeal joint of the foot)
•
Subcutaneous tophi—uric acid nodules
•
Uric acid urinary stones
Gout Clinical Features
•
Acute gout—acute attack of joint pain,
swelling, and inflammation
•
Chronic gout—tophi, deposits of uric acid
crystals in internal organ, urinary stones
The Nervous System
Major division - Central vs.
Peripheral
Central or CNS- brain and
spinal cord
Peripheral- nerves
connecting CNS to muscles
and organs
Central Nervous System
Peripheral Nervous System
Peripheral Nervous System
3 kinds of neurons connect
CNS to the body
Brain
Spinal
Cord
sensory
motor
interneurons
Motor - CNS to muscles and
organs
Sensory - sensory receptors to
CNS
Interneurons: Connections
Within CNS
Nerves
Peripheral Nervous System
Peripheral Nervous System
Skeletal
(Somatic)
Autonomic
Sympathetic
Parasympathetic
Somatic System
Brain
Nerves to/from spinal
cord
control muscle
movements
Sensory
Neuron
somatosensory inputs
Both Voluntary and
reflex movements
Skin receptors
Motor
Neuron
Interneuron
Skeletal Reflexes
Muscle
simplest is spinal reflex
arc
Autonomic System
Two divisions:
sympathetic
Parasympatheitic
Control involuntary functions
heartbeat
blood pressure
respiration
perspiration
digestion
Can be influenced by thought and emotion
Sympathetic
CENTRAL NERVOUS SYSTEM
“ Fight or flight” response
Release adrenaline and
noradrenaline
SYMPATHETIC
Brain
Dilates pupil
Stimulates salivation
Relaxes bronchi
Spinal
cord
Increases heart rate and
blood pressure
Salivary
glands
Lungs
Accelerates heartbeat
Inhibits activity
Increases blood flow to
skeletal muscles
Heart
Stomach
Pancreas
Stimulates glucose
Inhibits digestive functions
Secretion of adrenaline,
nonadrenaline
Relaxes bladder
Sympathetic
ganglia
Stimulates ejaculation
in male
Liver
Adrenal
gland
Kidney
Parasympathetic
CENTRAL NERVOUS SYSTEM
PARASYMPATHETIC
Brain
Contracts pupil
“ Rest and digest ”
system
Calms body to
conserve and
maintain energy
Lowers heartbeat,
breathing rate,
blood pressure
Stimulates salivation
Spinal
cord
Constricts bronchi
Slows heartbeat
Stimulates activity
Stimulates gallbladder
Gallbladder
Contracts bladder
Stimulates erection
of sex organs
Summary of autonomic
differences
Autonomic nervous system controls physiological arousal
Sympathetic
division (arousing)
Pupils dilate
Decreases
Parasympathetic
division (calming)
EYES
Pupils contract
SALVATION
Increases
Perspires
SKIN
Dries
Increases
RESPERATION
Decreases
Accelerates
HEART
Slows
Inhibits
DIGESTION
Activates
Secrete stress
hormones
ADRENAL
GLANDS
Decrease secretion
of stress hormones
Central Nervous System
Brain
Spinal
Cord
Brain and Spinal Cord
Brain has 2 Hemispheres
Corpus Callosum

Left & Right sides are separate

Corpus Callosum : major
pathway between hemispheres

Some functions are
‘lateralized’



Right
Hemisphere
language on left
math, music on right
Lateralization is never 100%
Left
Hemisphere
Each hemisphere is
divided into 4 lobes
Frontal
Parietal
Occipital
Temporal
Contralateral Motor Control
Movements controled
by motor area
Right hemisphere
controls left side of
body
Left hemisphere
controls right side
Motor nerves cross
sides in spinal cord
Motor Cortex
Somatosensory Cortex
Corpus Callosum
Major ( but not only) pathway
between sides
Medial surface of right hemisphere
Connects comparable
structures on each side
Permits data received on one
side to be processed in both
hemispheres
Aids motor coordination of left
and right side
Corpus Callosum
Corpus Callosum
What happens when the corpus callosum is
cut?
Sensory inputs are still crossed
Motor outputs are still crossed
Hemispheres can’t exchange data
Occipital Lobe
Input from Optic nerve
Occipital
Lobe
Contains primary visual
cortex
most is on surface
inside central
fissure
Outputs to parietal and
temporal lobes
Visual
Lobe
Temporal Lobe
 Contains primary auditory
cortex
Inputs are auditory, visual
patterns
Auditory
Cortex
speech recognition
face recognition
word recognition
memory formation
Outputs to limbic System,
basal Ganglia, and brainstem
Temporal
Lobe
Parietal Lobe
 contains primary
Inputs from multiplecortex
senses
somatosensory
 borders visual &
auditory cortex
 Outputs to Frontal lobe
 hand-eye coordination
 eye movements
 attention
Somatosensory
Parietal
Cortex
Lobe
Frontal Lobe
No direct sensory input
Important planning and
sequencing areas
Broca’s area for speech
Contains primary motor cortex
Prefrontal area for working
memory
Frontal
WorkingLobe
Broca’s
Memory
Area
Motor
Cortex
Frontal Lobe Disorders
Broca’s area
productive aphasia
Prefrontal area
lose track of ongoing context
fail to inhibit inappropriate responses
Often measured with the Wisconsin Card
Sorting Task
Dysraphic Developmental
Disorders
Figure 21-04
Cerebrovascular Diseases
•
Third most common cause of death
•
Most common crippling disease
•
Most important clinical manifestation—stroke
•
Disease of old age (atherosclerosis)
•
Arterial hypertension
•
Thromboembolism
Cerebrovascular Diseases
•
Global ischemia
•
Cerebral infarct
•
Intracerebral
hemorrhage
Figure 21-06
Cerebral Infarct
•
Caused by thrombotic occlusion and thromboemboli
•
Encephalomalacia
•
Pale infarct or hemorrhagic infarct
•
Surrounding brain tissue that is edematous
•
Fluid-filled cavity (“pseudocyst”)
•
Clinical presentation as stroke (e.g., contralateral
hemiplegia, sensory loss, global aphasia, drowsiness,
stupor, coma)
Multiple Sclerosis
•
Demyelinating disease
•
Women affected twice as often as men
•
Genetic factors
•
Oligoclonal T-cell populations in the brain
•
IgG in CSF composed of oligoclonal bands
Multiple Sclerosis
•
Chronic disease
•
Episodes of exacerbation and remission of neurologic symptoms
•
Sensory abnormalities
–
•
Motor abnormalities
–
•
Loss of sensitization of touch
Muscle weakness, unsteady gait, incoordination of movements,
sphincter abnormalities
Unpredictable course
Alcoholism
•
Wernicke-Korsakoff
syndrome
•
Uncoordinated
movements
•
Progressive mental
deterioration, loss of
memory, inability to
concentrate, irritability
•
Subdural hematoma,
pontine myelinolysis
Figure 21-13
Alzheimer’s Disease
•
Unknown etiology
•
Genetic factors—Down’s syndrome
•
Atrophy of the cortical parts of the frontal and
temporal parts of the brain
•
Disease of older people (>70 years)
•
Dementia—progressive loss of cognitive functions
and a functional decline (loss of memory
predominates)
Alzheimer’s Disease
•
Gross examination
–
•
The brain appears atrophic and shows narrowing of the gyri and
a widening of the sulci.
Histologic changes
–
Most prominent in the cortex
–
Neuritic (senile) plaques
–
Neurofibrillary tangles
–
Granulovacuolar degeneration
–
Deposition of amyloid in the neuritic plaques and the wall of the
cerebral vessels
Parkinson’s Disease
•
Subcortical neurodegenerative disorder
•
Typically affects elderly persons
•
Cause unknown
•
Decreased number of dopaminergic neurons in
the substantia nigra
•
Disturbances of movement, primarily tumor,
rigidity, bradykinesia, postural instability
Parkinson’s Disease
•
Tremor or twitching of the muscles
•
Instability while walking
•
Depression and dementia
–
•
Gross examination
–
•
Significant number of patients become depressed, and about 10% develop
dementia.
Substantia nigra appears pale.
Histologically
–
Loss of melanin-rich neurons
–
Lewy bodies
Huntington’s Disease
•
Autosomal dominant neurodegenerative
disease
•
Involuntary, gyrating movements and
progressive dementia
•
Atrophy of the cortex and subcortical nuclei,
most prominently the caudate and putamen
Huntington’s Disease
•
Nonspecific histologic changes include:
–
Atrophy, degeneration, loss of neurons,
reactive gliosis
•
First symptoms usually do not appear before
midlife.
•
Most affected patients become mentally
incapacitated by the age of 50 to 60 years.
Amyotrophic Lateral Sclerosis
•
Neurodegenerative disease
•
Affects older men and women
•
Motor weakness and progressive wasting of
muscles in the extremities (small hand
muscles)
•
Fasciculations (involuntary twitching)
•
Slurred speech but the intellect is not affected
Amyotrophic Lateral Sclerosis
•
Loss of motor neurons in the spinal cord,
midbrain, and cerebral cortex
•
Loss of the lateral cerebrospinal pathways in
the spinal cord
•
Incurable, progressive disease that leads to
death over a period of a few years
Glioblastoma Multiforme
•
Most common CNS tumor
•
Peak incidence—65 years
•
Lateral hemispheres
•
Gross appearance
–
Parts of the tumor are necrotic and yellow
–
Parts are hemorrhagic red, and parts are white
–
Irregularly shaped
–
Poorly demarcated
–
Butterfly-like appearance
Glioblastoma Multiforme
•
Histologically
–
Highly anaplastic astrocytic cells
–
Cell appearance—may retain a fetal
appearance or become enlarged, bizarre
shaped, or multinucleated with welldeveloped cytoplasm
–
Numerous mitotic figures
–
Proliferative changes of blood vessels
Meningioma
•
Arise from the meninges
•
Mostly benign
•
Located in the midline, at the base of the brain,
and along the spinal cord
•
Epileptic seizures or motor deficits
•
Excellent prognosis
Tricyclic Antidepressants



MOA:

Block the reuptake of monoamine NT (Dopamine) thus increasing their levels in
the synapse.

Possible that a subsequent downregulation of the receptors is the actual MOA

Interactions: Potentiate the effects of other CNS depressants and anticholinergic
drugs
Amitriptyline

Indications: major depressive disorder, enuresis, agoraphobia, OCD, migraines

Side Effects: severe anticholinergic effects, sedation
Imipramine

Indications: Enuresis in children. Was the TCA DOC but is no longer used due to
its side effects

Side Effects: similar to others but can induce arrhythmias
Selective Serotonin Reuptake
Inhibitors

Mechanism of action: Selectively inhibit the reuptake of
serotonin

Used for depression, OCD and Panic disorder

Fluoxetine (Prozac)

Sertraline (Zoloft)

Paroxetine (Paxil)
Stimulants


D-Amphetamine (Adderall and Dexedrine)

MOA: releases biogenic amines (NE, dopamine and serotonin) from
storage vesicles

Indications: narcolepsy, ADD

Side Effects: restlessness, insomnia, HTN, arrhythmia, anorexia,
psychotic episodes

Interactions: TCA potentiates the CNS effects by inhibiting the
metabolism of amphetamine

Special Notes: to treat OD you acidify the urine, give chlorpromazine
(Thorazine-sedation) to reduce CNS effects and an alpha blocker for the
HTN
Methylphenidate (Ritalin)

Same thing but milder stimulation
Parkinson’s Disease Drugs
 Levodopa
 MOA:
(L-Dopa)
is decarboxylated to dopamine (DA)
Improves
neuro, motor and psych s/sx of
parkinson’s
 Indications:
parkinson’s disease
 Side
Effects: N&V, modest ortho hypo,
arrhythmias in elderly, involuntary movements,
increased sexual activity
 Interactions:
pyridoxine (B6) reduces its effects,
antipsychotics block dopamine receptors,
anticholinergics delay absorption
 Special
notes: always used with carbidopa
Parkinson’s Disease Drugs

Carbidopa


MOA: deminishes the decarboxylation of L-Dopa in peripheral tissues
therefore increasing the effect of L-Dopa

Indications: Parkinson’s Dz

Side Effects: reduces the N&V associated with L-dopa

Interactions: None

Has no MOA when given alone
Amantadine

MOA: releases dopamine from intact terminals

Side Effects: at high doses hallucinations, confucion and nightmares

Interactions: anticholinergic drugs enhances the CNS side effects

Is less effective than L-Dopa but more effective than anticholinergics
Parkinson’s Disease Drugs
 Bromocriptine
 MOA:
powerful dopamine receptor agonist
 Indications:
Parkinson’s with tolerance to LDopa, hyperprolactinemia, pituitary tumors
 Side
Effects: N, hallucinations, hypotension
 Interactions:
carbidopa
can be used with L-Dopa and
Opioid Analgesics
 Morphine

MOA: opiate receptor agonist. Induces analgesia, sedation,
respiratory depression

Indications: severe pain not alleviated by non-narcotics. DOC for
severe pain in MI

Side Effects: respiratory depression, constipation, orthostatic
hypotension, cholestasis, constipation

Tolerance can develop to the analgesic effects but not the
constipating effects

Analgesia is threefold:

Increased threshold, unpleasant psych response is reduced, sleep is induced
Opioid Analgesics

Oxycodone (Oxycontin)
 MOA:
Same as morphine
 Indications:
 Side
moderate to severe pain
Effects: same as morphine
 Used
because it has a better oral absorption
than morphine
Benzodiazepines
 MOA:
bind to GABA receptors and enhances
GABA mediated neuronal inhibition. Causes
sedation, skeletal muscle relaxation and
barbiturate fast waves on EEG
 Indications:
anxiety, DT’s, seizures, relaxation of
Skeletal muscles
 Side
Effects: drowsiness, clouding of
consciousness, ataxia, behavioral disinhibition,
dermatitis
 Interactions:
effects are additive with ETOH
Benzodiazepines



Diazepam (Valium)

Is long acting

Indicated for anxiety disorder
Midazolam (Versed)

Is short acting

Used in anesthesia
Alprazolam (Xanax)

Short acting

Used as an antidepressant and an anxiolytic

Used to treat panic attacks

Does not cause daytime drowsiness
Migraine Headache Therapy

Sumatriptan (Imitrex)
 MOA:
serotonin receptor agonists
 Causes
vasoconstriction of the basilar artery and dura
matter vessels
 Onset
of relief is 10 minutes – two hours
 Side
Effects: dizziness, tingling, flushing, chest
discomfort, weakness and neck pain
 Used
to treat a migraine that is already occurring
 Propranolol
migraine
and timilol are used to prevent the onset of a