Exam 2 Flashcards
1
Q
The autonomic nervous system is part of the nervous system and is
composed of the Sympathetic and the Parasympathetic systems.
A
The autonomic nervous system is part of the nervous system and is
composed of the Sympathetic and the Parasympathetic systems.
2
Q
The autonomic nervous system, along with the endocrine system, exerts
control over the functions of many organs and tissue in the body.
A
The autonomic nervous system, along with the endocrine system, exerts
control over the functions of many organs and tissue in the body.
3
Q
Autonomic Nervous System (ANS)
Innervates visceral organs (smooth muscles), glands and blood vessels
A
Innervates visceral organs (smooth muscles), glands and blood vessels
4
Q
Autonomic Nervous System (ANS)
Controls the function of different visceral organs and regulates them.
A
Controls the function of different visceral organs and regulates them.
5
Q
Autonomic Nervous System (ANS)
It has afferent and efferent pathways.
A
It has afferent and efferent pathways.
6
Q
Autonomic Nervous System (ANS)
The efferent fibers have their cell bodies in the spinal cord, and they
reach the sympathetic ganglia on both sides of the vertebral column.
A
The efferent fibers have their cell bodies in the spinal cord, and they
reach the sympathetic ganglia on both sides of the vertebral column.
7
Q
Autonomic Nervous System (ANS)
The parasympathetic efferents reach their ganglia at or near the organs.
A
The parasympathetic efferents reach their ganglia at or near the organs.
8
Q
Function of the ANS
Sympathetic and Parasympathetic
A
Functions at most part at the subconscious level
*Sympathetic system:
prepares and mobilizes the body in emergency cases
e.g.: during exercise, fear…
Sympathetic stimulation leads to:
increased heart rate, constriction of the arterioles of the skin and intestine,
(but, dilatation of those of the skeletal muscle), which raises the blood pressure, sympathetic stimulation leads to dilation of the pupils, sphincters close, hair stands and sweating occurs.
*Parasympathetic system:
conserves and stores the energy
e.g.: during sleep
Parasympathetic stimulation leads to :
Decrease in heart rate, pupil constriction, increased peristalsis, increased
glandular activity, sphincters open, bladder wall is contracted.
9
Q
Function of the ANS
Sympathetic
A
Functions at most part at the subconscious level
*Sympathetic system:
prepares and mobilizes the body in emergency cases
e.g.: during exercise, fear…
Sympathetic stimulation leads to:
increased heart rate, constriction of the arterioles of the skin and intestine,
(but, dilatation of those of the skeletal muscle), which raises the blood pressure, sympathetic stimulation leads to dilation of the pupils, sphincters close, hair stands and sweating occurs.
10
Q
Function of the ANS
Parasympathetic
A
Functions at most part at the subconscious level
*Parasympathetic system:
conserves and stores the energy
e.g.: during sleep
Parasympathetic stimulation leads to :
Decrease in heart rate, pupil constriction, increased peristalsis, increased
glandular activity, sphincters open, bladder wall is contracted.
11
Q
Organization of the ANS
A
- Synapses between neurons are made in the autonomic ganglia.
- -Parasympathetic ganglia are located in or near the effector organs.
- -Sympathetic ganglia are located in the paravertebral chain. - Preganglionic neurons have their cell bodies in the CNS and synapse in autonomic ganglia.
- preganglionic neurons of the sympathetic nervous system originate in spinal cord segments T1-L3, or the thoracolumbar region.
- Preganglionic neurons of the parasympathetic nervous system originate in the nuclei of cranial nerves and in spinal cord segments S2-S4, or the craniosacral region.
- Postganglionic neurons of both divisions have their cell bodies in the autonomic ganglia and synapse on effector organs (heart, blood vessels, sweat glands
- Adrenal medulla is a specialized ganglion of the sympathetic nervous system.
- Preganglionic fibers synapse directly on chromaffin cells in the adrenal medulla.
- The chromaffin cells secrete epinephrine (80%) and norepinephrine (20%) into the circulation.
* Pheochromocytoma is a tumor of the adrenal medulla that secretes excessive amounts of catecholamines and with increased excretion of 3-methoxy-4-hydroxymandelic acid (VMA).
12
Q
Anatomical organization
of the ANS:
A
Efferent sympathetic outflow:
Sympathetic: (thoraco-lumbar)
Origin: cell bodies lie the lateral horn
of the T1- L2/3 spinal cord.
Parasympathetic: (cranio-sacral)
Origin: CN III, CN VII, CNIX and CN X
and S1, S2, S3 (pelvic splanchnic nerve).
13
Q
Anatomical organization
Sympathetic system:
A
Efferent sympathetic outflow:
Origin: cell bodies lie the lateral horn
of the T1- L2/3 spinal cord.
14
Q
Receptors
Sympathetic and Parasympathetic Systems
A
Sympathetic system: Adrenergic receptors : Alpha receptors: α-1 and α-2 Beta receptors: β-1 and β-2 Dopamine receptors: D1 and D2
Parasympathetic system:
Cholinergic receptors:
Nicotinic receptors
Muscarinic receptors
15
Q
Receptors
Parasympathetic System
A
Parasympathetic system:
Cholinergic receptors:
Nicotinic receptors
Muscarinic receptors
16
Q
Receptors
Sympathetic System
A
Sympathetic system: Adrenergic receptors : Alpha receptors: α-1 and α-2 Beta receptors: β-1 and β-2 Dopamine receptors: D1 and D2
17
Q
Neurotransmitters of the
Autonomic Nervous System
A
Neurotransmitters :
- Adrenergic neurons release norepinephrine as the neurotransmitter.
- Cholinergic neurons, whether in the sympathetic or parasympathetic nervous system, release acetylcholine (Ach) as the neurotransmitter.
- Peptidergic neurons in the parasympathetic nervous system release peptides such as vasoactive inhibitory peptide and substance P.
18
Q
Receptor types in the Autonomic Nervous System
Adrenergic receptors (adrenoreceptors)
Alpha 1 receptors
A
- are located on vascular smooth muscle of the skin and splanchnic regions, the gastrointestinal (GI) and bladder sphincters, and the radial muscle of the iris.
- produce excitation (contraction ,constriction).
Are equally sensitive to norepinephrine and epinephrine. However, only norepinephrine released from adrenergic neurons is present in high enough concentration to activate alpha 1 receptors.
Mechanism of action : G protein alpha stimulator, Phospholipase C, formation of inositol 1,4,5-triphospate (IP3) and increase in intracellular (Ca+).
The effect of a neurotransmitter or endocrine hormone depends on the type AND location of the receptor
(clinical point)
over secretion of alpha 1 or over secretion of NE leads to hypertension
19
Q
Receptor types in the Autonomic Nervous System
Adrenergic receptors (adrenoreceptors)
Alpha 2 receptors
A
- are located in presynaptic nerve terminals, platelets. Fat cells, and the walls of the GI tract.
- often produce inhibition (relaxation or dilation).
- Mechanism of action: G protein alpha inhibitor, inhibition of adenylate cyclase and decrease in cyclic adenosine monophosphate (CAMP).
Presynaptic nerve terminal = neuron
20
Q
Receptor types in the Autonomic Nervous System
Adrenergic receptors (adrenoreceptors)
Beta 1 receptors
A
- are located in the sinoatrial (SA) node, atrioventricular (AV) node, and ventricular muscle of the heart.
- produce excitation (increased heart rate, increased conduction velocity, increased contractility).
- are sensitive to both norepinephrine and epinephrine, and are more sensitive than alpha1 receptors.
- Mechanism of action: activation G protein alpha stimulator, activation of adenylate cyclase and increase in cAMP.
Location: heart
(clinical point)
over stimulation of B1 or over secretion of NE leads to palpitation, tachycardia, arrythmia
Treatment: B1 blocker
medicine: propranolol
blocks step 1 of NE/B1 drawing
If patient has palpitation or heart problem and at the same time is asthmatic you CAN NOT give them propranolol recognizes the B2 and blocks the B2 which has side effect on bronchi
instead give patient medicine: Atenolol
Atenolol is only B1 blocker so asthma and heart problem patient can utilize it
21
Q
Receptor types in the Autonomic Nervous System
Adrenergic receptors (adrenoreceptors)
Beta 2 receptors
A
- are located on vascular smooth muscle of skeletal muscle, bronchial smooth muscle, and in the walls of the GI tract and bladder.
- produce relaxation (dilation of vascular smooth muscle, dilation of bronchioles, relaxation of the bladder wall.)
- are more sensitive to epinephrine than to norepinephrine.
- are more sensitive to epinephrine than the alpha 1 receptors.
- Mechanism of action: same as for beta 1 receptors.
B2 agonist
Medicine: Albuterol
acts as B2 and can be used in place of B2 to relax bronchi
22
Q
Receptor types in the Autonomic Nervous System
Cholinergic receptors (cholinoreceptors)
Nicotinic receptors
A
- are located in the autonomic ganglia of the sympathetic and parasympathetic nervous systems, at the neuromuscular junction, and in the adrenal medulla. The receptors at these are similar, but not identical.
- are activated by Ach or nicotine.
- produce excitation.
- are blocked by ganglionic blockers in the autonomic ganglia, but not at the neuromuscular junction.
- Mechanism of action: Ach binds to alpha subunits of the nicotinic Ach receptor, The nicotinic Ach receptors are also ion channels for Na+ and K+.
23
Q
Receptor types in the Autonomic Nervous System
Cholinergic receptors (cholinoreceptors)
Muscarinic receptors
A
- are located in the heart, smooth muscle, and glands.
- are inhibitory in the heart (decreased heart rate, decreased conduction velocity in AV node).
- are excitatory in smooth muscle and glands (increased GI motility, increased secretion).
- are activated by Ach and muscarine.
- are blocked by atropine.
-Mechanism of action:
Heart SA node: inhibition of adenylate cyclase, which leads to opening of K+ channels, slowing of the rate of spontaneous Phase 4 depolarization, and decreased heart rate
- Smooth muscle and glands: formation of IP3 and increase in intracellular (Ca2+).
24
Q
Autonomic centers-brain stem and hypothalamus
A
- Medulla
- Vasomotor center
- Respiratory center
- Swallowing, coughing, and vomiting centers - Pons
- Pneumotaxic center - Midbrain
- Micturition center - Hypothalamus
- Temperature regulation center
- Thirst and food intake regulatory centers
Pneumotaxiv = respiratory system
Micturition = renal system
Hypothalamus memory, learning, sexual behavior connected to limbic system(emotional behavior) body temperature endocrine system
25
Neurotransmitters of the
| Autonomic Nervous System
Neurotransmitters act on their receptors in various tissues
Preganglionic:
Acetylcholine (Ach)
Postganglionic:
Parasympathetic: Ach
Sympathatic:
Norepinephrine (NA)
26
Adrenergic Receptors
Beta receptors: β-1
Located in the heart
Stimulates rate and force
27
Adrenergic Receptors
Beta receptors: β-2
In vascular ,bronchial ( smooth m.) ,GI tract, Relaxes
Liver Stimulates glycogenolysis
Pancreatic B cells Stimulates insulin release
B2 = bronchi, liver, beta cells in Pancreas
28
Adrenergic Receptors
α-1: (postsynaptic)
Located on Vascular smooth muscle contraction
Pupillary smooth M contraction (mydriasis)
pilomotor smooth M contraction (erects hair)
29
Adrenergic Receptors
α-2: (mostly presynaptic)
On Adrenergic and cholinergic nerve terminals
-inhibits transmitter release
fat cells -inhibits lipolysis
platelets -stimulates aggregation
Some smooth muscle(presynaptic inhibition of parasympathetic) -contraction
30
Cholinergic receptors
Muscarinic
```
in Glands +ve effect, heart –ve effect,
smooth muscle (except vascular smooth muscle) +ve effect like peristalsis
```
Mechanism of action: increased intracellular calcium
31
Cholinergic receptors
Nicotinic
At the neuromuscular junction
Produce excitation (opening of Na-K channels, depolarization)
32
Effect of ANS on Eye
Pupil
Sympathetic = α-receptor: Dilatation
Parasympathetic = Constriction
Ciliary muscle
Sympathetic = β-rec: Accommodation Parasympathetic = Contraction
Lacrimal gland
S = decreased secretion P = increase secretion
----
Sympathetic
controls dilation of pupil by Alpha 2
Accommodation = Beta 2
blocks tear secretion of lacrimal glands to eyes
33
Salivary glands
Submandibular
S = α-receptor: Activates viscous secretion
P = activates secretion of watery saliva
Parotid
S = Vasoconstrictor
P = activates secretion of watery saliva
Sublingual
S = decreased secretion
P = increase secretion
----
Salivary glans secrete saliva. Sympathetic AND parasympathetic(both) increase saliva secretion by different mechanisms.
34
Heart(know these)
Coronary Arteries
S = β1-rec: +ve Chronotropic, β1-rec: +ve Dromotropic, vasodilation
P = -ve Chronotropic, -ve Dromotropic , vasoconstriction
----
```
Sympathetic
increase heartrate
+ve Chronotropic = heart rate
positive effect on Chronotropic
increases contractility of conduction velocity(dromotropic)
Vasodilation
```
```
Parasympathetic
Vagus nerve and Acetylcholine
decreases heartrate
negative effect of chronotropic
decreases conduction velocity(dromotropic)
```
35
Lung
Bronchi(muscle)
S = β2-receptor: Dilatation
P = Constrictor
Vessels
S = Constriction
P = Dilation
Glands
S = decreases secretion
P = increases secretion
36
GI tract
Peristalsis (tonus)
S = β2-receptor: Relaxation
P = Activation
Sphincters
S = α-receptor: Constriction
P = Relaxation
```
Glands
S = decreases secretion
P = increases secretion
----
Parasympathetic is more active usually
Vagus nerve and Acetylcholine
increases peristalsis and gastric hormones
```
37
Liver
```
S = β-rec: Gluconeogenesis
P = Glycogenesis
```
38
Gall Bladder
Sphincters
S = β2-receptor : Relaxation
P = constriction
----
Parasympathetic
main neurotransmitter is Acetylcholine
CCK is a second neurotransmitter
39
Pancreas
Insulin
S = α-receptor: inhibits it’s secretion
S = β-receptor: activates it’s secretion
P = nothing
Exocrine
S = α-receptor: inhibits it’s secretion
P = Activates secretion
----
Everything is controlled by sympathetic but activation of exocrine enzymes is by parasympathetic
40
Adrenal medulla
S = Activates secretion
P = nothing
----
Adrenal medulla is an exception
Only by preganglionic fiber of sympathetic nervous system
Acetylcholine
stimulates norepinephrine/epinephrine AKA noradrenaline/adrenaline hormones
Innervation is by preganglionic fiber of sympathetic
41
Urinary bladder
Sphincter M.
S = α-receptor: contraction
P = relaxation
Detrusor M.
S = β-receptor: relaxation
P = contraction
----
Sympathetic
filling of urinary bladder
Parasympathetic
emptying of bladder
42
Uterus
Pregnant
S = α-receptor: contraction
P = nothing
Non-pregnant
S = β-receptor: relaxation
P = nothing
----
Just under control of sympathetic
A1 – pregnant female
B2 – nonpregnant female
43
Male/Female Genitals
```
S = ejaculation(emission)
P = Erection(vasodilatation)
```
----
Emission = internal circulation in male
Sympathetic
Erection
parasympathetic
Ejaculation
both sympathetic and parasympathetic
44
Sensory Systems
-are specialized epithelial cells or neurons that transduce environmental signals into
neural signals.
-The enviromental signals that can be detected
include mechanical force, light, sounds, chemicals, and temperature.
----
The second part of nervous system is sensory
Specific ion channels and receptors are needed.
45
Types of sensory transducers
1- Mechanoreceptors: respond to mechanical stimulus
- Pacinian corpuscles
- joint receptors
- Stretch receptors in muscle
- Hair cells in auditory and vestibular systems
- Baroreceptors in carotid sinus
2-Photoreceptors
-Rods and cones of the retina
3. Chemoreceptors
- Olfactory receptors
- Taste receptors
- Osmoreceptors
- Carotid body O2 receptors
4. Extremes of temperature and pain
- Nociceptors
46
Types of sensory transducers
1- Mechanoreceptors
respond to mechanical stimulus
- Pacinian corpuscles
- joint receptors
- Stretch receptors in muscle
- Hair cells in auditory and vestibular systems
- Baroreceptors in carotid sinus
47
Types of sensory transducers
2-Photoreceptors
-Rods and cones of the retina
48
Types of sensory transducers
3. Chemoreceptors
- Olfactory receptors
- Taste receptors
- Osmoreceptors
- Carotid body O2 receptors
49
Types of sensory transducers
4. Extremes of temperature and pain
-Nociceptors
50
Fiber types and conduction velocity
-A-alpha
-large alpha-motoneurons
Conduction velocity: fastest
-A-beta
Touch, pressure
Conduction velocity: Medium
-A-gamma
gamma-motoneurons to muscle spindles (intrafusal fibers)
Conduction velocity: Medium
-A-delta
Touch, pressure, temperature, and pain
Conduction velocity: Medium
-B
preganglionic autonomic fibers
Conduction velocity: Medium
-C
Slow pain, postganglionic autonomic fibers
Conduction velocity: Slowest
----
Type A – alpha is fastest receptor
Type C – slowest receptor
All others are medium conduction
51
Fiber types and conduction velocity
-A-alpha
-A-alpha
-large alpha-motoneurons
Conduction velocity: fastest
52
Fiber types and conduction velocity
-A-beta
-A-beta
Touch, pressure
Conduction velocity: Medium
53
Fiber types and conduction velocity
-A-gamma
-A-gamma
gamma-motoneurons to muscle spindles (intrafusal fibers)
Conduction velocity: Medium
54
Fiber types and conduction velocity
-A-delta
-A-delta
Touch, pressure, temperature, and pain
Conduction velocity: Medium
55
Fiber types and conduction velocity
-B
-B
preganglionic autonomic fibers
Conduction velocity: Medium
56
Fiber types and conduction velocity
-C
Slow pain, postganglionic autonomic fibers
| Conduction velocity: Slowest
57
Receptive field
-is an area of the body that, when stimulated, changes the firing rate of a sensory neuron. If the firing rate of the sensory neuron is increased, the receptive field is excitatory. If the firing rate of the sensory neuron is *decreased, the receptive field is inhibitory.
58
Steps in sensory transduction
a. Stimulus arrives at the sensory receptor.( photon of light on the retina, a molecule of NaCl on the tongue).
B. Ion channels are opened in the sensory receptor, allowing current to flow.
Usually the current is inward, which is depolarization of the receptor.
C. The change in membrane potential produced by the stimulus is the receptor potential, or generator potential.
59
Adaptation of sensory receptors
a. Slowly adapting, or tonic, receptors (muscle spindle, pressure, slow pain)
- respond repetitively to a prolonged stimulus.
B. Rapidly adapting, or phasic, receptors (pacinian corpucle, light touch)
-show a decline in action potential frequency with time in response to a constant stimulus.
60
Sensory pathways from the sensory receptor to the cerebral cortex
A. Sensory receptors
A. Sensory receptors
- are activated by environmental stilmuli.
- may be specialized epithelial cells (taste receptors, auditory hair cell).
- may be primary afferent neurons (olfactory chemoreceptors).
- transduce the stimulus into electrical energy ( receptor potential).
61
Sensory pathways from the sensory receptor to the cerebral cortex
B. First-order neurons
B. First-order neurons
-are the primary afferent neurons that receive the transduced signal and send the information to the CNS. Cell bodies of the primary afferent neurons are in dorsal root or spinal cord ganglia.
62
Sensory pathways from the sensory receptor to the cerebral cortex
C. Second-order neurons
C. Second-order neurons
- are located in the spinal cord or brain stem.
- receive information from one or more primary afferent neurons in relay nuclei and transmit it to the thalamus.
- Axons of second-order neurons usually cross the midline in a relay nucleus in the spinal cord before they ascend to the thalamus. Therefore, sensory information originating on one side of the body ascends to the contralateral thalamus.
63
Sensory pathways from the sensory receptor to the cerebral cortex
D. Third-order neurons
D. Third-order neurons
-are located in the relay nuclei of the thalamus. From there, encoded sensory information ascends to the cerebral cortex.
64
Sensory pathways from the sensory receptor to the cerebral cortex
E. Fourth-order neurons
E. Fourth-order neurons
-are located in the appropriate sensory area of the cerebral cortex.
The information received results in a conscious perception of the stimulus.
65
Somatosensory system
The somatosensory system processes information about touch, pain and temperature.
Somatosensory pathways
1. Dorsal column system
2. Anterolateral system
Type of somatosensory receptors
1. Mechanoreceptors (for touch)
2. Thermoreceptors (temperature)
3. nociceptors (pain)
----
Somatosensory pathways
Dorsal Column system
Anterolateral system
66
Pathways in the somatosensory system
Dorsal column system
-processes sensations of fine touch, pressure, two-point discrimination, vibration.
Course: primary afferent neurons have cell bodies in the dorsal root. Their axons ascend ipsilaterally to the nucleus gracilis and nucleus cuneatus of the medulla.
From the medulla the second-order neurons cross the midline and ascend to the contralateral thalamus, where they synapse on third-order neurons.
Third-order neurons ascend to the somatosensory cortex, where they synapse on fourth-order neurons.
----
Detects fine touch, pressure, two point discrimination and vibration
67
Pathways in the somatosensory system
Anterolateral system
- processes sensations of temperature, pain, and light touch.
- consists primarily of group of fibers, which enter the spinal cord and terminate in the dorsal horn.
- second-order neurons cross the midline to the anterolateral quadrant of the spinal cord and second to the contralateral thalamus, where they synapse on third-order neurons.
- Third-order neurons ascend to the somatosensory cortex, where they synapse on fourth-order neurons.
----
Detects temperature, pain, and light touch
68
Thalamus
- Information from different parts of the body is arranged somatotopically.
* Destruction of the thalamic nuclei results in loss of sensation on the contralateral side of the body.
69
Thalamus
Pain
- is associated with the detection and perception of noxious stimuli (nociception).
- The receptors for pain are free nerve endings in the skin, muscle, and viscera.
- Neurotransmitters for nociceptors include substance P. Inhibition of the release of substance P is the basis of pain relief by opioids.
A. Fibers for fast pain and slow pain
- Fast pain is carried by group A-delta fibers. It has a rapid onset and offset, and is localized.
- Slow pain is carried by C fibers. It is characterized as aching, burning, or throbbing that is poorly localized.
B. Referred pain
-Pain of visceral origin is referred to sites on the skin and follow the dermatome rule. These sites are innervated by nerves that arise from the same segment of the spinal cord.
For example: ischemic heart pain is referred to the chest and shoulder.
----
Clinical point
If there is any damage to a side of the thalamus(right thalamus) then patient has a sensory disorder on LEFT side of the body
Referred pain
retrosternum pain, left shoulder, left arm, last 2 fingers pain, submandibular pain
myocardial infarction
70
Two-point touch threshold
If each point touches the receptive fields of different sensory neurons, two separate points of touch will be felt. If both caliper points touch the receptive field of one sensory neuron, only one point of touch will be felt.
71
Taste and Smell
The senses of Gustation (taste) and Olfaction (smell) fall under the category of Chemoreception.
Specialized cells act as receptors for certain chemical compounds.
Gustation and Olfaction are chemical senses because the receptors they contain are sensitive to the molecules in the food we eat, along with the air Gustatory System
72
In humans, the sense of taste is transduced by taste buds and is conveyed via three of the twelve cranial nerves.
1. Cranial nerve VII, the facial nerve, carries taste sensations from the anterior two thirds of the tongue and soft palate.
2. Cranial nerve IX the glossopharyngeal nerve carries taste sensations from the posterior one third of the tongue.
3. Also a branch of the vagus nerve carries some taste sensations from the back of the oral cavity (i.e. pharynx and epiglottis).
Dendritic endings of these nerves are located around the taste buds and relay sensations of touch and temperature. Taste sensations are passed to the medulla oblongata, where the neurons synapse with second-order neurons that project to the thalamus, from here, third-order neurons project to the area of the postcentral gyrus of the cerebral cortex that is devoted to sensations from the tongue.
73
Types of Taste
Salt
Sour
Bitter
Sweet
74
Types of Taste
Salt
Arguably the simplest receptor found in the mouth is the salt (NaCl) receptor. An ion channel in the taste cell wall allows Na+ ions to enter the cell. This on its own depolarizes the cell, and opens voltage-regulated Ca2+ gates, flooding the cell with ions and leading to neurotransmitter release.
75
Types of Taste
Sour
Sour taste signals the presence of acidic compounds (H+ ions in solution). There are three different receptor proteins at work in sour taste. The first is a simple ion channel which allows hydrogen ions to flow directly into the cell.
76
Types of Taste
Bitter
Bitter compounds act through structures in the taste cell walls called G-protein coupled receptors (GPCR’s). When the bitter compound activates the GPCR, it in turn releases gustducin, the G-protein it was coupled to.
77
Types of Taste
Sweet
Like bitter tastes, sweet taste transduction involves GPCR’s.
78
Disorders of the Tongue
Ageusia
Hypogeusia
Hypergeusia
Ageusia (Loss of taste):You may lose your sense of taste if the facial nerve is damaged.
Hypogeusia (decreased taste sensitivity)
Hypergeusia (increased taste sensitivity)
79
Disorders of the Tongue
Sore tongue
It is usually caused by some form of trauma, such as biting your tongue, or eating piping-hot or highly acidic food or drink.
If your top and bottom teeth don’t fit neatly together, tongue trauma is more likely.
Some people may experience a sore tongue from grinding their teeth (bruxism).
Disorders such as diabetes, anemia, some types of vitamin deficiency and certain skin diseases can include a sore tongue among the range of symptoms.
----
Sore tongue is often found in alcoholic patients
destruction of taste buds by alcohol
80
Disorders of the Tongue
Glossodynia
A condition characterized by a burning sensation on the tongue.
81
Disorders of the Tongue
Benign migratory glossitis
This condition is characterized by irregular and inflamed patches on the tongue surface that often have white borders. The tongue may be generally swollen, red and sore. Another name for this condition is geographic tongue. The cause of benign migratory glossitis is unknown.
82
Olfactory System
A. Receptor cells
- are located in the olfactory epithelium.
| - are true neurons that conduct action potentials into the CNS.
83
Olfactory System
B. CN I (olfactory)
- carries information from the olfactory receptor cells to the olfactory bulb.
- The axons of the olfactory nerves are unmyelinated C fibers and are among the smallest and slowest in the nervous system.
- Olfactory epithelium is also innervated by CN V (trigeminal), which detects noxious or painful stimuli, such as ammonia.
The olfactory nerves pass through the cribriform plate on their way to the olfactory bulb. Fractures of the cribriform plate sever input to the olfactory bulb and reduce (hyposmia) or eliminate (anosmia) the sense of smell. The response to ammonia, however, will be intact after fracture of the cribriform plate because this response is carried on CN V.
----
Between nasal cavity and brain
the membrane called the cribriform plate
ontop of the plate is the olfactory bulb(yellow color) which continues to olfactory tract
the bulb is penetrated by receptors to nasal cavity
84
Olfactory System
C. Mitral cells in the olfactory bulb
- are second-order neurons.
| - output of the mitral cells forms the olfactory tract, which projects to the cortex.
85
Steps in transduction in the olfactory receptor neurons
A. Odorant molecules bind to receptors located on cilia of the olfactory receptor neurons.
B. When the receptors are activated, they activate G proteins (G olf), which in turn activate adenylate cyclase.
C. There is an increase in intracellular (cAMP) that opens Na+ channels in the olfactory receptor membrane and produces a depolarizing receptor potential.
D. The receptor potential depolarizes the initial segment of the axon to threshold, and action potentials are generated and propagated.
----
When odor binds to olfactory receptors it leads to depolarization of receptors and release stimulatory neurotransmitter.
The stimulatory neurotransmitter stimulates the first group of neurons which pass through the cribriform plate and enters the olfactory bulb
the first group of cells is called Mitral cells
Mitral cells have synapse with second group of cells in olfactory tract and the second group of neurons travel to the olfactory center which is located at the base of the olfactory tract.
mitral cells reach olfactory bulb by passing through the cribriform plate
Mitral cells interact with second group of neurons which travels to the olfactory tract
then after olfactory tact group 2 reaches olfactory center located at the base of the olfactory tract
depolarization of cells is by opening of Na+ channels and Na+ inflow to cells
86
Disorders of Olfaction
Anosmia
Anosmia is the lack of olfaction, or a loss of the sense of smell.
----
Detection of pain in olfactory is by CN 5(trigeminal nerve)
87
Disorders of Olfaction
Phantosmia
Phantosmia is the phenomenon of smelling odors that aren't really present.
88
Disorders of Olfaction
Dysosmia
When things smell differently than they should.
89
Anatomy of the Eye
The human eye is a elongated ball about 1-inch (2.5 cm) in diameter and is protected by a bony socket in the skull. The eye has three layers or coats that make up the exterior wall of the eyeball, which are the sclera, choroid, and retina.
90
Sclera
The outer layer of the eye is the sclera, which is a tough white fibrous layer that maintains, protects and supports the shape of the eye. The front of the sclera is transparent and is called the cornea. The cornea refracts light rays and acts like the outer window of the eye.
----
Sclera is connective tissue for protection of eye from external trauma
ventrally it continues with cornea
Between pupil and corner is the anterior chamber
91
Vision
The visual waves.
The eye can distinguish two qualities of light:
- its brightness
- its wavelength, for human, the wavelengths between 400 and 750 nanometers are called visible light.
Structures of the Eyesclera, choroid, and retina,
92
Choroid
The middle thin layer of the eye is the choroid, it is the vascular layer of the eye lying between the retina and the sclera. The choroid provides oxygen and nourishment to the outer layers of the retina. It also contains a nonreflective pigment that acts as a light shield and prevents light from scattering.
----
Second layer of eye
full of blood vessels because it gives nutrients to eye
Continues ventrally with iris
iris are the pigment cells
Behind iris is the posterior chamber and lens
Superior part of iris there is ciliary muscle and ciliary body
ciliary body released fluid into posterior chamber then anterior chamber
the fluid from anterior chamber is released into venous system through channel of Schlemm
Schlemm is connection between anterior chamber and venous system
Clinical Point
obstruction of channel of Schlemm is glaucoma
could be congenital, infection, tumor, head trauma
signs/symptoms
accumulation of intraocular fluid in anterior and posterior chambers
untreated glaucoma leads to increased intraocular pressure and effects the retina and optic nerve which leads to blindness
the problem must be solved early or blindness
surgery to cut some ligaments which are connected to the channel of Schlemm
93
Retina
The third or the inner layer of the eye is call the retina. The retina lays over the back two thirds of the choroid coat, which is located in the posterior compartment. The compartment is filled with vitreous humor which is a clear, gelatinous material.
Within the retina there are cells called rod cells and cone cells also known as photoreceptors.
* The rod cells are very sensitive to light and do not see color, that is why when we are in a darkened room we see only shades of gray.
* The cone cells are sensitive to different wavelengths of light, and that is how we are able to tell different colors. It is a lack of cones sensitive to red, blue, or green light that causes individuals to have deficiencies in color vision or various kinds of color blindness.
At the center of the retina is the optic disc, sometimes known as "the blind spot" because it lacks photoreceptors. It is where the optic nerve leaves the eye and takes the nerve impulses to the brain.
The cornea and the lens of the eye focuses the light onto a small area of the retina called the **fovea centralis** where the cone cells are densely packed. The fovea is a pit that has the highest visual acuity and is responsible for our sharp central vision - there are no rods in the fovea.
----
Third(innermost) layer of eye
Full of neurons
Comprised of 6 layers
The central artery and vein of retina are in the optic nerve
The blind spot has a lack of rod and cone cells
94
Layers of the retina:
1. Pigment epithelial cell
- absorb stray light and prevent scatter of light.
2. Receptor cells are rods and cones
3. Bipolar cells. The receptor cells (rods and cones) synapse on bipolar cells, which synapse on the ganglion cells.
4. Horizontal cells
5. Amacrine cells for circuits with the bipolar cells.
6. Ganglion cells are the output cells of the retina. (*Axons of ganglion cells form the optic nerve).
----
Review 6 layers of retina
The axon of ganglion cells together form the optic nerve
The photoreceptors are cone and rod cells
Rod detects light(sensitive to it)
Cone detects the wavelength of light(detects color)
95
Steps in photoreception in the rods
-The photosensitive element is rhodopsin, which is composed of scotopsin (a protein) and retinal (an aldehyde of vitamin A).
A. light on the retina converts 11-cis retinal to all-trans retinal, a process called photoisomerization. A series of intermediates in then formed, one of which is metarhodopsin II.
- Vitamin A is necessary for the regeneration of 11-cis retinal. Deficiency of vitamin A causes night blindness.
- Metarhodopsin II activates G protein (transducin), which in turn activates a phosphodiesterase.
- Phosphodiesterase decrease cGMP.
- Decreased levels of cGMP cause closure of Na+ channels, decreased inward Na+ current--- Hyperpolarization----decreased release of either an exitatory neurotransmitter or an inhibitory neurotransmitter.
1. If the neurotransmitter is exitatory, then the response of the bipolar or horizontal cell to light is hyperpolarization.
2. If the neurotransmitter is inhibitory, then the response of the bipolar or horizontal cell to light is depolarization.
----
Cone cells are similar but for color
Step 1(know this)
closure of Na+ channels
when light is absorbed by rod cells then the closure of Na+ channels occurs
There is NO depolarization of rod cells which can not release inhibitory neurotransmitter
because of this the light is able to pass from rod cell to bipolar cell
bipolar cell is the next layer
bipolar cell is able to absorb the signal and pass to horizontal cell
horizonal cell is able to pass to amacrine cell
amacrine cell to ganglion cell
when ganglion cell receive the light signal it release the stimulatory neurotransmitter Glutamate
by releasing the neurotransmitter the optic nerve is stimulated
the optic nerve then takes the signal to different stations in brain
the last station is the occipital lobe of the brain
area 171819 AKA primary visual area
When there is no light then we have opening of Na+ channels then rod cells release inhibitory neurotransmitter
inhibits stimulation of bipolar and other layers
no signal to optic nerve
There are similar molecules in CONE cells BUT cone cells are sensitive to wavelength of light
96
Optic Pathways
The optic pathways from the retina to the CNS:
Axons from retinal ganglion cells form the optic nerves and optic tracts, synapse in the lateral geniculate body of the thalamus, and ascend to the visual cortex in the geniculocalcarine tract (occipital lob, area 17, 18, 19).
-----
The signals that come from left temporal field focuses on nasal portion of retina on left eye, then it passes through optic chiasm then it travels to contralateral optic tract which reaches lateral geniculate nucleus in thalamus. Then it has synapse with next group of neurons. The next group of neurons travels to primary visual area in occipital lobe
(repeats for right side)the signal from right temporal field focuses on nasal portion of retina of right eye then it passes through optic chiasm. It reaches lateral geniculate nucleus and has synapse with next group of neurons. The next neuron travels to primary visual area(area 17, 18, 19)
The signal that comes from left nasal field focuses on temporal portion of retina. It travels to ipsilateral optic tract to geniculate nucleus where it synapses with next group of neuron. The next group of neurons travels to primary visual cortex.
(repeats for right side) Signal from right nasal field….etc
The name of tract after thalamus is called the geniculocalcarine tract
97
Color Blindness
Color Blindness or color vision deficiency, in humans is the inability to perceive differences between some or all colors that other people can distinguish. It is most often of genetic nature, but may also occur because of eye, nerve, or brain damage, or due to exposure to certain chemicals.
-----
Any damage to cone cells = color blindness
98
Night blindness
Night blindness may exist from birth, or be caused by injury or malnutrition (for example, a lack of vitamin A). The most common cause of nyctalopia is retinitis pigmentosa, a disorder in which the rod cells in the retina gradually lose their ability to respond to the light.
-----
Any damage to rod cells = night blindness
99
Glaucoma
Intracranial pressure
-----
Glaucoma – obstruction or closure of channel of Schlemm
100
Visual Agnosia
Visual agnosia is the inability of the brain to make sense of or make use of some part of otherwise normal visual stimulus, and is typified by the inability to recognize familiar objects or faces.
101
Emmetropia
normal.
Light focuses on the retina.
102
Hypertropia
farsighted.
light focuses behind the retina and is corrected with a convex lens.
-----
Hypertropia = not able to see close objects
103
Myopia
nearsighted.
Light focuses in front of the retina and is corrected with a biconcave lens.
-----
Myopia = not able to see far
104
Astigmatism
Curvature of the lens is not uniform and is corrected with a cylindric lens.
105
Anatomy of the Ear
The ear has three divisions: the outer ear, middle ear, and the inner ear.
----
The middle ear is connected to meningeal layer. Any infection(bacterial, viral) in middle ear then patient has risks for bacterial or viral meningitis
106
Anatomy of the Ear
Outer Ear
Auricle, Ear Canal, Surface of Ear Drum
The outer ear is the most external portion of the ear.
107
Anatomy of the Ear
Middle Ear
is air-filled.
The middle ear includes most of the ear drum (tympanic membrane) and the 3 ear bones ossicles: malleus (or hammer), incus (or anvil), and stapes (or stirrup). The opening of the Eustachian tube is also within the middle ear.
The malleus has a long process (the handle) that is attached to the mobile portion of the ear drum.
The incus is the bridge between the malleus and stapes. The stapes is the smallest named bone in the human body. The stapes transfers the vibrations of the incus to the oval window, a portion of the inner ear to which it is connected.
108
Anatomy of the Ear
Inner Ear
is fluid-filled.
(Cochlea, Vestibule, and Semi-Circular Canals, and a series of ducts called the membranous labyrinth. The fluid outside the ducts is perilymph; the fluid inside the ducts is endolymph.
109
Structure of the cochlea: three tubular canals
A. The scala vestibuli and scala tympani contain perilymph, which has a high Na+.
B. The scala media contains endolymph, which has a high K+.
–The scala media is bordered by the basilar membrane, which is the site of the organ of Corti.
110
Location and structure of the organ of Corti
- The organ of Corti is located on the basilar membrane.
- It contains the receptor cells for auditory stimuli. Cilia protrude from the hair cells and are embedded in the tectorial membrane.
- Inner hair cells are arranged in single rows and are few in number.
- Outer hair cells are arranged in parallel rows and are greater in number than inner hair cells.
- The spiral ganglion contains the cell bodies of the auditory nerve CN VIII which synapse on the hair cells.
Sound waves cause vibration of the organ of Corti--- bending of the cillia causes depolarization----firing of cochlear nerves.
111
Steps in auditory transduction by the organ of Corti
The cell bodies of hair cells contact the basilar membrane. The cilia of hair cells are embedded in the tectorial membrane.
A. Sound waves cause vibration of the organ of Corti. Because the basilar membrane is more elastic than the tectorial membrane, vibration of the basilar membrane causes the hair cells to bend by a shearing force as they push against the tectorial membrane.
B. Bending of the cilia causes changes in K+ conductance of the hair cell membrane. Bending in one direction causes *hyperpolarization, bending in the other direction causes *depolarization. The oscillating potential that results is the cochlear microphonic potential.
C. The oscillating potential of the hair cells causes intermittent firing of the cochlear nerves.
112
How sound is encoded
-the frequency that activates a particular hair cells depends on the location of the hair cell along the basilar membrane.
A. The base of the basilar membrane (near the oval and round windows) is narrow and stiff. It responds best to high frequencies.
B. The apex of the basilar membrane (near the helicotrema) is wide and compliant. It responds best to low frequencies.
113
Audition
Sound waves
- Frequency is measured in hertz (Hz).
- Intensity is measured in decibels (dB)
dB =20 log P/Po
dB= decibel
P =sound pressure being measured
Po=reference pressure measured at the threshold frequency
114
Auditory pathways
Information is transmitted from the hair cells of the organ of Corti to the afferent cochlear nerves. The cochlear nerves synapse on neurons of the dorsal and ventral cochlear nuclei of the medulla, which send out axons that ascend in the CNS. Some of these axons cross to the contralateral side and ascend in the lateral lemniscus (the primary auditory tract) to the inferior colliculus. Other axons remain ipsilateral.
The two inferior colliculi are connected via the commissure of the inferior colliculus. Fibers from nuclei of the inferior colliculus ascend to the medial geniculate nucleus of the thalamus. Fibers from the thalamus ascend to the auditory cortex (area 41, 42, temporal lob).
-----
After depolarization of hair cells the hair cell releases stimulatory neurotransmitter which stimulates the first group of neurons of cochlear nerve which travel to spinal ganglion. First group of nerves synapses with next group of neurons. Second group of neurons travel to medulla oblongata ventral/ dorsal nuclei for cochlear nerve where they synapse with next group of neurons. Third group of neurons, some travel to contralateral stations in contralateral temporal lobe. The next group of neurons(ipsilateral) pass through pons through the lateral lemniscus tract. Then they travel from pons to midbrain. In midbrain the Superior and Inferior Colliculi. Then they synapse with next neuron which then travels to medial geniculate nucleus to synapse with next group of neurons. This neuron travels to superior gyrus of temporal lobe of brain. Specifically area 41 and 42(primary auditory area).
115
Otitis Media
An inflammation of the middle ear segment. It is usually associated with a buildup of fluid and frequently causes an earache. The fluid may or may not be infected. The typical progress of otitis media is: the tissues surrounding the Eustachian tube swell due to an infection and/or severe congestion. The Eustachian tube remains blocked most of the time. The air present in the middle ear is slowly absorbed into the surrounding tissues. A strong negative pressure creates a vacuum in the middle ear. The vacuum reaches a point where fluid from the surrounding tissues accumulates in the middle ear.
Etiology
Streptococcus pneumoniae and Haemophilus influenzae are the most common bacterial causes of otitis media. As well as being caused by Streptococcus pneumoniae and Haemophilus influenzae it can also be caused by the common cold.
----
When there is any infection in middle ear due to bacteria or virus leads to spreading of bacteria to meningeal layer of brain
non treated the patient can be led to bacterial or viral meningitis
bacterial meningitis
streptococcus
116
Vestibular system
- detects angular and linear acceleration of the head.
| - reflex adjustments of the head, eyes, and postural muscles provide a stable visual image and steady posture.
117
Structure of the vestibular organ
A. It is a membranous labyrinth consisting of three perpendicular semicircular canals, a utricle, and a saccule. The semicircular canals detect angular acceleration or rotation. The utricle and saccule detect linear acceleration.
B. The canals are filled with endolymph and are bathed in perilymph.
C. The receptors are hair cells located at the end of each semicircular canal. Cilia on the hair cells are embedded in a gelatinous structure called the cupula. A single long cilium is called the Kinocilium; smaller cilia are called stereocilia.
118
Steps in vestibular transduction – angular acceleration
A. During counterclock wise (left) rotation of the head the horizontal semicircular canal and its attached cupula also rotate to the left. Initially, the cupula moves more quickly than the endolymph fluid.
Thus, the cupula is dragged through the endolymph; as a result, the cilia on the hair cells bend.
B. If the stereocilia are bent toward the kinocilium, the hair cell depolarizes (excitation). If the stereocilia are bent away from the kinocilium, the hair cell hyperpolarizes (inhibition). Therefore, during the initial counterclockwise (left) rotation, the left horizontal canal is excited and the right horizontal canal is inhibited.
C. After several seconds, the endolymph catches up with the movement of the head and the cupula. The cilia return to their upright position and are no longer depolarized or hyperpolarized.
D. When the head suddenly stops moving, the endolymph continues to move counterclockwise (left, dragging the cilia in the opposite direction. Therefore, if the hair cell was depolarized with the initial rotation, it now will hyperpolarize. If it was hyperpolarized initially, it now will depolarize. Therefore, when the head stops moving, the left horizontal canal will be inhibited and the right horizontal canal will be excited.
119
Vestibular pathways
Afferent nerves from vestibular hair cells terminate in vestibular nuclei of the medulla: the superior, medial, lateral, and inferior nuclei.
- Medial and superior nuclei receive their input from the semicircular canals and project to nerves innervating extraocular muscles via the medial longitudinal fasciculus.
- The lateral vestibular nucleus receives input from the utricles and project to spinal cord motoneurons via the lateral vestibulospinal tract. Projections of the lateral vestibular nucleus play a role in maintaining postural reflexes.
- The inferior vestibular nucleus receives its input from the utricles, saccules, and semicircular canal. It project to the brain stem and the cerebellum via the medial longitudinal fasciculus.
120
Vestibular –ocular reflexes
a. Nystagmus
- An initial rotation of the head causes the eyes to move slowly in the opposite direction to maintain visual fixation. When the limit of eye movements reaches, the eyes rapidly snap back (nystagmus), then move slowly again.
- The direction of the nystagmus is defined as the direction of the fast (rapid eye) movement. Therefore, the nystagmus occurs in the same direction as the head rotation.
B. Post-rotatory nystagmus
-occurs in the opposite direction of the head rotation.
121
Vertigo (dizziness)
Vertigo is usually associated with a problem in the inner ear balance mechanisms (vestibular system), in the brain, or with the nerve connections between these two organs.
122
What happens if the person turns the head to the right side.
1. Endolymph initially goes to the opposite direction (left)
2. Cupula also goes to the opposite direction (left)
3. Cupula returns to normal position when adaptation is achieved
4. When the head stops rotation, endolymph moves to the same direction of the head turning.
5. Cupula goes to same direction (the direction of head turning) until movement of endolymph stops and cupula returns to normal position.
123
Cells of the Nervous tissue:
Two main cell types
Cells are densely packed and intertwined.
- Neurons: transmit electrical signals, found in grey matter of CNS and ganglia.
- Neuroglial cells (support cells): nonexcitable, surround and wrap neurons.
Neurons are basic structural units of the nervous system and
possess a cell body and processes called neurites.
Human body contains billions of neurons.
```
----
Neuron is able to have action potential
receive stimulus from outside source
oxygen and glucose
glucose is best
```
124
Characteristics of Neurons:
Conduct electrical impulses along the plasma membrane
Produce nerve impulse
Produce action potential
Longevity: can live and function for a lifetime
Do not divide: fetal neurons lose their ability to undergo mitosis
High metabolic rate: require abundant oxygen and glucose
125
Structure of a neuron:
```
1- cell body (perikaryon)
Size varies from 5–140µm
Has the normal cell organelles
*Nissl bodies (rER),
Neurofibrils and Lipofuscin
```
```
2- axon (long)
Transmits impulses away from
Neuron. Neuron has only one axon
No protein synthesis in axon
No Nissl bodies in axoplasm.
Initial segment: after Axon hillock;
most excitable site, origination
site of action potential.
Neurofilaments, microtubules and
actin microfilaments are present.
Is smooth, without many synapses.
Axon terminal (buttons).
```
```
3- dendrite (short)
Increases neuron’s receptive area.
Transmits impulses towards the
Neuron.
Nissl bodies in its basal parts.
```
126
Structure of a neuron:
1- cell body (perikaryon)
Size varies from 5–140µm
Has the normal cell organelles
*Nissl bodies (rER),
Neurofibrils and Lipofuscin
127
Structure of a neuron:
2- axon (long)
```
Transmits impulses away from
Neuron. Neuron has only one axon
No protein synthesis in axon
No Nissl bodies in axoplasm.
Initial segment: after Axon hillock;
most excitable site, origination
site of action potential.
Neurofilaments, microtubules and
actin microfilaments are present.
Is smooth, without many synapses.
Axon terminal (buttons).
```
128
Structure of a neuron:
3- dendrite (short)
Increases neuron’s receptive area.
Transmits impulses towards the
Neuron.
Nissl bodies in its basal parts.
129
Supporting cells
There are two types of supporting cells in the peripheral nervous system:
- Provide supportive functions for neurons.
- Cover nonsynaptic regions of the neurons.
a. Schwann cells, which form myelin sheaths around peripheral axons.
b. Satellite cell, or ganglionic gliocytes, which support neuron cells bodies within the ganglia of the PNS.
130
Supporting cells
There are four types of supporting cells, called neuroglial cells, in the central nervous system.
a. Oligodendrocytes, which form myelin sheaths around axons of the CNS.
b. Microglia, which migrate through the CNS and phagocytose foreign and degenerated material.
c. astrocytes, which help to regulate external environment of neurons in the CNS
d. Ependymal cells, which line the ventricles of the brain and the central canal of the spinal cord.
131
Supporting cells
Oligodendrocytes (Oligs):
```
small cell bodies, no filaments in their
cytoplasm, one oligodendrocyte can
myelinate many fibers.
Oligodendrocytes are not surrounded
by a basement membrane, unlike the
Schwann cells in PNS.
```
132
Functions of Oligs:
1- Myelination in the CNS
Oligodendrocytes that surround nerve
cell bodies, (Stellite Oligs) may influence
the biochemical environment of neurons.
133
Microglia:
Smallest among neuroglial cells. Migrate
into the nervous system in fetal life.
They are scattered in the CNS.
134
Functions of microglia:
In the normal CNS, they are inactive
(resting microglia) but, in inflammation or
degeneration of CNS, they proliferate and
become active and phagocytic.
135
Ependyma:
Form a single layer of cuboidal cells lining the
central cavities of the brain and spinal cord.
They have microvilli also.
-----
Ependymal cells cover internal environment of ventricles
accelerate the circulation of CSF
136
Supporting cells
CNS glia:
Astrocytes:
small cell body, numerous branching processes.
Many astrocytic processes are interwoven at inner and outer surfaces of CNS, forming
outer and inner glial limiting membranes.
137
Function of the astrocytes:
1- They form a supportive framework for neurons, and in embryo they serve as a
scaffolding for migration of immature neurons.
2- they cover the synaptic contacts between neurons and thus insulate axon terminals from influencing neighboring unrelated neurons.
3- They absorb glutamate (transformed into glutamine) and GABA secreted by the nerve terminals, thus limiting the influence of these neurotransmitters.
4- They absorb excess K+ of extracellular fluid. Since K+ diffuses out of neurons during the production of nerve impulses, for maintaining the proper ionic environment for neurons.
5- By feet surrounding blood capillaries take up glucose from the blood, the glucose metabolized into lactic acid, is then released and use as an energy source by neurons.
6- Phagocytosis of degenerated axon terminals.
7- replacement gliosis: when neurons die due to disease or injury, they proliferate and fill the spaces previously occupied by neurons.
8-Astrocytes induce the formation of the blood-brain barrier.
9- produce trophic substances for neurons.
-----
Clinical point
astrocyte cell proliferation which occupies part of brain tissue inhibits regeneration of axon in CNS
this is why CNS can not regeneration but PNS can
138
Supporting cells (Neuroglia) :
Types of neuroglial cells in PNS:
1- Satellite cells:
Surround neuron cell bodies within ganglia
2- Schwann cells:
Surround axons in the PNS
Form myelin sheath around axons of the PNS
139
Gliosis and glial scar:
Gliosis is hyperplasia and hypertrophy of astrocytes that occur in reaction to CNS injury.
Oligodendrocytes: respond to injury by expanding and vacuolation of their cytoplasm.
140
Tumors of Neuroglia (glioma):
Account for about 50% of intracranial tumors. Astrocytomas and glioblastomas are tumors of astrocytes. Gliomas apart from ependymomas are very invasive and grow large with minimal effect on neighboring neurons.
141
Multiple sclerosis (Demyelinating diseases of the CNS) :
An unknown disease, occurs between ages of 20-40 year, demyelination in CNS, usually starts with optic nerve, spinal cord and cerebellum. Axonal degeneration as a result of demyelination and/or early in the course of the disease is part of the disability.
142
Neurilemma and myelin sheath
Myelin sheath in PNS and CNS
The myelin sheaths of the CNS are formed by oligodendrocytes. This process occurs mostly postnatally. Showann cells form the myelin sheaths of PNS*.
Unlike a Schwann cell, which forms a myelin sheath around only one axon, each oligodendrocyte has extensions, form myelin sheaths around several axons.
The myelin sheaths around axons of the CNS give this tissue a white color, areas of the CNS that contain a high concentration of axons thus form the white matter.
The gray matter of the CNS is composed of high concentrations of cell bodies and dendrites, which lack myelin sheaths.
-----
M.S.
due to damaged myelin sheath
inhibits axon potential in neurons
if phrenic nerve(C3-5) is impacted then diaphragm can not function = death
no myelin sheath then action potential is decreased
patient has motor and sensory disorders
143
Regeneration of a Cut axon
When an axon in peripheral nerve is cut, the distal portion of the axon that was severed from the cell body degenerates and is phagocytosed by Schwann cells. The schwann cell, surrounded by the basement membrane, then form a regeneration tube, as the part of the axon that is connected to the cell body begins to grow and exhibit amoeboid movement. The SC secrete chemicals that attract the growing axon tip, and the regeneration tube helps to guide the regeneration axon to its proper destination.
In CNS, Regeneration is more limited , due in part to the absence of a continuous neurilemma (as is present in the PNS), which to inhibitory molecules produced by oligodendrocytes and astrocytes in the injured CNS
-----
Astrocytes in CNS interfere with regeneration in CNS
not present in PNS so can have nerve regenration
144
Neurotrophins
In a developing fetal brain, chemicals called neurotrophins promote neuron growth:
- Nerve growth factor (NGF)
- Brain-derived neurotrophic factor (BDNF)
- Glial-derived neurotrophic factor (GDNF)
- Neurotrophin-3(it is important in the embryonic development of sensory neurons and sympathetic ganglia.)
-----
Know the 4 names on this slide
145
Blood-Brain Barrier (BBB)
The blood-brain barrier (BBB) is the barrier between cerebral capillary blood and the CSF. CSF fills the ventricles and the subarachnoid space.
-It consists of the endothelial cells of the cerebral capillaries and the choroid plexus epithelium.
----
Separates the capillary tissue from brain
Large size proteins can not pass BBB
Alcohol can pass BBB(being drunk)
146
Physiology BBB
Formation of CSF by the choroid plexus epithelium
Lipid-soluble substances (CO2 and O2) and H2O freely cross the blood-brain barrier and equilibrate between blood and CSF.
- Other substances are transported by carriers in the choroid plexus epithelium. They may be secretedfrom blood into the CSF or absorbed from the CSF into blood.
- Protein and cholesterol are excluded from the CSF because of their large molecular size.
- The composition of CSF is approximately the same as that of the interstitial fluid of the brain, but differs significantly from blood.-CSF can be sampled with a lumbar puncture.
147
Function of the blood-brain barrier
It maintains a constant environment for neurons in the CNS and protects the brain from endogenous or exogenous toxins.
It prevents the escape of neurotransmitters from their functional sites in the CNS into the general circulation.
Drugs penetrate the blood-brain barrier to varying degrees. For example, nonionized (lipid-soluble) drugs cross more readily than ionized (water-soluble) drugs.
Inflammation, irradiation, and tumors may destroy the blood-brain barrier and permit entry into the brain of substances that are usually excluded (antibiotics. radiolabeled markers).
For example, L-DOPA, the precursor to dopamine, can cross the BBB, whereas dopamine itself cannot. (e.g., Parkinson's disease)
----
Some medicines are not able to pass BBB
dopamine
Parkinsons disease needs dopamine replacement
L-dopa is used as it can pass through BBB then neuron can use it to make dopamine
148
Comparison of cerebrospinal fluid (CSF) and blood concentrations
CSF=Blood
Na+
Cl-
HCO3-
Osmolarity
CSF has same amount
149
Comparison of cerebrospinal fluid (CSF) and blood concentrations
CSF< blood
```
K+
Ca2+
Glucose
Cholestrol*
Protein*
```
CSF has less
CSF has more
150
Comparison of cerebrospinal fluid (CSF) and blood concentrations
CSF> blood
Mg2+
Creatinine
CSF has more
151
Synapses:
Nervous system consists of neurons that are
linked together to form functional conducting
pathways. Synapses are the sites where two
neurons come into close proximity.
The term also implies to the nerve-muscle
contact as well.
----
Chemical synapses has neurotransmitters involved which has presynaptic and postsynaptic compartments
after stimulation of presynaptic then it releases neurotransmitter(stimulatory or inhibitory) which has action on postsynaptic compartment
152
Various forms of synapses:
```
Axodendritic, axosomatic and axoaxonic.
The first two are the most common forms.
Axons can have a terminal expansion or a
series of expansions called bouton de
passage which make several contacts as
they pass through a dendritic tree.
```
153
Types of synapses:
1- Chemical (most common)
| 2- Electrical
154
Chemical synapses
involve the neurotransmitters
released from a pre-synaptic neuron that becomes attached to a protein (receptor) at post-synaptic membrane.
Chemical synapses are unidirectional.
----
Chemical synapses has neurotransmitters involved which has presynaptic and postsynaptic compartments
after stimulation of presynaptic then it releases neurotransmitter(stimulatory or inhibitory) which has action on postsynaptic compartment
155
Ultrastructure of chemical
| synapses:
```
e opposed surfaces of terminal axonal
expansion and the neuron are termed the
presynaptic and postsynaptic (with sub
synaptic web) membranes, respectively,
and are separated by a synaptic cleft (20-
30nm). Membranes are thicker here.
Presynaptic cytoplasm contains vesicles,
mitochondria and lysosomes among others.
On postsynaptic side, the cytoplasm
contains parallel cysternae.
Synaptic cleft contains polysaccharides.
```
156
Neurotransmitters at chemical synapses:
The presynaptic vesicles contain the neurotransmitter substance and the mitochondria
provide ATP for neurotransmitter synthesis.
Neurotransmitters: Acetylcholine (Ach), norepinephrine, epinephrine, dopamine,
glycine, serotonin, gamma-aminobutyric acid (GABA), enkephalines, substance P
and glutamic acid.
The majority of neurons produce and release only one principal neurotransmitter.
----
Glycine and GABA are the only two inhibitory neurotransmitters
they stimulate chloride channels
Cl- is negative ion which makes the inside of cell extremely negative and inhibits action potential
157
Distribution of neurotransmitters:
Ach: is found at neuromuscular junction, in autonomic ganglia, parasympathetic nerve,
Norepinephrine: found at sympathetic nerve endings, in CNS: in hypothalamus.
Dopamine: found in high concentrations in basal ganglia and hypothalamus.
Glycine: is found principally in synapses in the spinal cord.
Glutamate: is an excitatory amino acid neurotransmitter in many central nervous
neurons.
158
Action of neurotransmitters:
Neurotransmitters are released from the
nerve endings after the nerve being
stimulated (arrival of action potential).
This results in an influx of Ca++ ions
into the presynaptic part which causes
the synaptic vesicles to fuse with the
presynaptic membrane.
The neurotransmitters are then released
into the synaptic cleft, increasing or
decreasing the resting potential of the
postsynaptic membrane for a short time.
The receptor on postsynaptic membrane
binds the neurotransmitter which opens the
ion channels, generating an excitatory
postsynaptic potential (EPSP) e.g.: in case
of Ach in nicotinic receptors or inhibitory
postsynaptic potential (IPSP) in case
of GABA for example.
Other receptors bind the neurotransmitter
and activate a 2nd messenger system such
as a G-protein (response lasts for minutes).
Examples: Ach (muscarinic), serotonin,
neuropeptides and adenosine (neuromodulators).
159
Fate of the neurotransmitters:
Neurotransmitters effect for a short time since they are either destructed in the cleft or reabsorbed by the presynaptic part (e.g.: Ach in the synaptic cleft is destructed by Acetylcholinesterase (AChE).
In case of Catecholamines, the effect is limited by their return to the presynaptic ending.
160
Characteristics of a neurotransmitter:
1- presence of the substance within neuron terminals
2- release of the substance with neuronal stimulation
3- application of the exogenous substance to the postsynaptic membrane produces
the effects of stimulation of the presynaptic neuron.
4- the concentration –response curve of the substance applied to the postsynaptic
membrane is affected by drugs in a similar way as normal postsynaptic response.
5- a local mechanism exists for inactivation of the substance (e.g.: enzymatic
degradation, uptake into nerve terminal or glia).
161
Electrical synapses:
Most synapses in the nervous system are of chemical type with neurotransmitter, but in electrical synapses, there is no chemical
transmitters.
These synapses are Gap junctions formed by specialized channels called Connexons.
Each Connexon consists of 6 parts called Connexins.
These channels are from cytoplasm of the presynaptic neuron to that of the postsynaptic neuron which allow the flow of ionic current
between cells with minimal delay.
These are found in a group of neurons performing an identical function.
These are bidirectional.
```
----
Gap junction(connexons) acts as a channel for ions
```
162
reatment of certain neurological diseases by neurotransmitters:
Parkinson could be Treated to some extent by neurotransmitters.
Dopamine can not cross the BBB. L-dopa can cross BBB.
163
Synaptic blocking agents:
transmission of nerve impulses is due to release of
neurotransmitters into synaptic cleft, activating the postsynaptic membrane.
Transmission can be easily blocked; long chain neurons with multiple synapses are
easier to block. General anesthetics block synaptic transmission.
Local anesthetics block nerve conduction when applied locally; by interfering with the
transient increase in permeability of the axolemma to Na+, K+ and other ions.
Small nerve fibers are more sensitive and slower to recover.
Phenothiazines block Dopamine receptors postsynaptically.
164
Monoamines as Neurotransmitters
The regulatory molecules are:
- Epinephrine
- Norepinephrine
- Dopamine
- Serotonin
165
Serotonin as a neurotransmitter
Serotonin, a master neurotransmitter, is manufactured from tryptophan. It is found all over the body and is necessary to modulate the levels of the stress hormones.
In the central nervous system, serotonin is believed to play an important role in the regulation of anger, aggression, body temperature, mood, sleep, vomiting, sexuality, and appetite. Low levels of serotonin may be associated with several disorders:
- namely increase in aggressive and angry behaviors
- clinical depression
- migraine
- bipolar disorder, anxiety disorders
If neurons of the brainstem that make serotonin—serotonergic neurons—are abnormal, there is a risk of sudden infant death syndrome.
*Serotonin taken orally does not pass into the serotonergic pathways of the central nervous system because it does not cross the blood-brain barrier.
166
Dopamine as a neurotransmitter
In the brain, dopamine functions as a neurotransmitter, activating the five types of dopamine receptor - D1, D2, D3, D4 and D5, and their variants.
Dopamine is produced in several areas of the brain:
- Substantia nigra
- Dopamine is also a neurohormone released by the hypothalamus. Its main function as a hormone is to inhibit the release of prolactin from the anterior lobe of the pituitary.
- Dopamine can be supplied as a medication that acts on the sympathetic nervous system, producing effects such as increased heart rate and blood pressure.
- dopamine cannot cross the blood-brain barrier, dopamine given as a drug does not directly affect the central nervous system.
- To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease
* L-DOPA (levodopa), which is the precursor of dopamine, can be given because it can cross the blood-brain barrier.
167
Function of Dopamine in the brain
- Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson's disease (in which a person loses the ability to execute smooth, controlled movements).
- attention deficit disorder (prefrontal cortex).
Regulating prolactin secretion (Dopamine produced by neurons in the arcuate nucleus of the hypothalamus).
Dopamine is commonly associated with the pleasure system of the brain. Dopamine is released (particularly in areas such as the nucleus accumbens).
- abnormally high dopamine action apparently leading to these conditions (schizophrenia).
168
Norepinephrine as a neurotransmitter
- It is released from the adrenal medulla of the adrenal glands as a hormone into the blood,
- but it is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons during synaptic transmission.
-As a stress hormone, it affects parts of the human brain where attention and responding actions are controlled.
Along with epinephrine, norepinephrine underlies the fight-or-flight response, directly increasing heart rate, triggering the release of glucose from energy stores, and increasing skeletal muscle readiness.
169
Amino acids as neurotransmitters
Excitatory neurotransmitters
an excitatory postsynaptic potential (EPSP) is a temporary depolarization of postsynaptic membrane potential caused by the flow of positively charged ions into the postsynaptic cell.
They are the opposite of inhibitor postsynaptic potentials (IPSPs), which usually result from the flow of negative ions into the cell. A postsynaptic potential is defined as excitatory if it makes it easier for the neuron to fire an action potential.
The neurotransmitter most often associated with EPSPs is the amino acid glutamate, and is the main excitatory neurotransmitter in the central nervous system.
170
Amino acids as neurotransmitters
Inhibitory neurotransmitters
An Inhibitory Postsynaptic Potential (commonly abbreviated as IPSP) is the change in membrane voltage of a postsynaptic neuron which results from synaptic activation of inhibitory neurotransmitter receptors.
The most common inhibitory neurotransmitters in the nervous system are GABA and glycine.
171
Neuropeptide Y
Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system. It augments the vasoconstrictor effects of noradrenergic neurons.
NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy.
It forms part of the "lipostat" system along with leptin and corticotropin-releasing hormone (CRH).
----
Hormone leptin in fat tissue helps control appetite
Neuropeptide Y and Leptin controls appetite
172
Nitric oxide and carbon monoxide as neurotransmitters
NO is one of the few gaseous signaling molecules known. It is a key biological messenger, playing a role in a variety of biological processes.
Nitric oxide, known as the 'endothelium-derived relaxing factor is biosynthesized from arginine and oxygen by various nitric oxide synthase (NOS) enzymes and by reduction of inorganic nitrate.
The endothelium (inner lining) of blood vessels use nitric oxide to signal the surrounding smooth muscle to relax, thus dilating the artery and increasing blood flow.
The production of nitric oxide is elevated in populations living at high-altitudes, which helps these people avoid hypoxia.
Effects include blood vessel dilatation, neurotransmission, modulation of the hair cycle, and penile erections.
----
NO is a vasorelaxor/vasodilator
Deficiency of NO and prostaglandin can lead to erectile dysfunction
173
CNS is divided into 3 parts
motor – innervation of muscles
sensory - senses
autonomic – innervates internal organs in thoracic, abdominal, pelvic, endocrine glans(some), sweat glands, blood vessels, blood pressure
sympathetic and parasympathetic
Sympathetic
when body is active
running, dancing, hiking, diving, etc
adjust for the elevated activity conditions
running = excess sweating, increased heart rate increased respiratory rate
relaxes smooth muscle of bronchi
Parasympathetic
when body is resting
sleeping
decreases heart rate, decreases myocardial contractions
more active in GI tract for digestion, absorption
increases motility of GI
secretion of gastric hormones, gastric acid
174
Anatomical Organization of the ANS
The red color is location of sympathetic
T1-L2/3 of spinal cord
sympathetic AKA thoraco-lumbar
Parasympathetic(AKA Cranio-sacral) has 2 parts
Cranial
nuclei for some cranial nerves
CN 3, 7(facial), 9, and 10(vagus)
Vagus nerve has 3 nuclei in brain stem(know this)
Sensory, Motor, Autonomic
Autonomic nuclei is for parasympathetic system
Sacral AKA pelvic splanchnic nerve
some say S1-3 but for our class S2-S4
innervates pelvic organs
175
Two types of fibers(must know this info)
preganglionic fiber
releases neurotransmitter Acetylcholine(Ach)
name of receptor = Cholinergic Receptor
postganglionic fiber
releases norepinephrine or noradrenaline
name of receptor = Adrenergic receptor
176
Parasympathetic
pre and post ganglionic meet into the wall of organs
the pre ganglionic fiber of parasympathetic fiber is longer than pre ganglionic fiber of sympathetic system
Parasympathetic
pre and post ganglionic meet into the wall of organs
the pre ganglionic fiber of parasympathetic fiber is longer than pre ganglionic fiber of sympathetic system
177
(study these)Differences between parasympathetic and sympathetic
Origin
sympathetic T1-L2/3
parasympathetic = cranio-sacral
synapsis between pre and post ganglionic fibers is different
sympathetic = inside sympathetic chain
para sympathetic = synapsis occurs inside wall of internal organs most of the time
preganglionic fiber of parasympathetic is longer than preganglionic fiber of sympathetic
preganglionic fiber of sympathetic release Acetylcholine(Ach) and postganglionic fiber of sympathetic release norepinepherine(aka noradrenaline)
but pre and post ganglionic fibers of parasympathetic release Acetylcholine(Ach)
when body is active sympathetic active
body not active = parasympathetic
the name of receptor cholinergic is for Ach
renergic is for norepinephrine
**the effect of a neurotransmitter or hormone depends on the type of receptor AND location of the receptor
178
Parasympathetic increases in activity in GI
increases peristalsis, gastric hormone secretion, HCl secretion
Neurotransmitter secreted by pre and post
Ach
179
Clinical Point
over secretion of alpha 1 or over secretion of NE leads to hypertension
over secretion of alpha 1 or over secretion of NE leads to hypertension
180
(clinical point)
| over stimulation of B1 or over secretion of NE leads to palpitation, tachycardia, arrythmia
over stimulation of B1 or over secretion of NE leads to palpitation, tachycardia, arrythmia
Treatment: B1 blocker
medicine: propranolol
blocks step 1 of NE/B1 drawing
If patient has palpitation or heart problem and at the same time is asthmatic you CAN NOT give them propranolol recognizes the B2 and blocks the B2 which has side effect on bronchi
instead give patient medicine: Atenolol
Atenolol is only B1 blocker so asthma and heart problem patient can utilize it
181
Sensory pathway explanation
The sensory receptors and located in peripheral organs
for example, skin
When the sensory receptor receive stimulus from outside
After stimulus this leads to stimulation of first group of neurons which is connected to base of receptor
The first group of neurons takes the information about sensory to the spinal cord
the dorsal horn of spinal cord – center for sensory
Then they enter spinal cord
Some of the first group neurons have synapse with second group of neurons inside the spinal cord
Some of the first group of neurons without synapse continue to travel to brain stem
Then they have synapse with second group of neurons
The second group of neurons then travel to contralateral thalamus
pinching left hand by the right side of thalamus catches information
Contralateral thalamus has contact with third group of neurons
The third group of neurons travels to cerebral cortex(brain) and they reach the sensory center in brain where they have synapse with fourth group of neursons
182
Clinical point
If there is any damage to a side of the thalamus(right thalamus) then patient has a sensory disorder on LEFT side of the body
Referred pain
retrosternum pain, left shoulder, left arm, last 2 fingers pain, submandibular pain
myocardial infarction
Clinical point
If there is any damage to a side of the thalamus(right thalamus) then patient has a sensory disorder on LEFT side of the body
Referred pain
retrosternum pain, left shoulder, left arm, last 2 fingers pain, submandibular pain
myocardial infarction
183
```
Taste
Anterior
receptor for sweet
bi lateral
receptor for sour
hydrogen ion channels
Anterior lateral
Salty
Base of tongue
Bitter
```
```
Taste
Anterior
receptor for sweet
bi lateral
receptor for sour
hydrogen ion channels
Anterior lateral
Salty
Base of tongue
Bitter
```
184
Tongue Innervation
```
Innervation by 3 cranial nerves
Anterior 2/3 of tongue
I: CN 7(facial nerve)
branch: Chordatympani
Posterior 1/3 of tongue
I: CN 9(glossalpharyngeal
Base(connected to pharynx)
I: Vagus nerve(CN 10)
```
185
Taste Requirements
Salt
need NaCl
Sour
hydrogen ion
Bitter and Sweet
G-protein coupled receptors
186
Functions of muscle tissue
1- Movement
Skeletal muscle: attached to skeleton, moves body by moving the bones
Maintenance of posture: enables the body to remain sitting or standing
Smooth muscle: squeezes fluids and other substances through hollow organs
2- Joint stabilization
3- Heat generation: contractions produce heat, keeps normal body temperature
-----
Overstimulation of alpha 1 can lead to hypertension
187
Types of muscles:
Three types
1- Skeletal muscle tissue: packaged into skeletal muscles
Makes up 40% of body weight. Cells are striated
2- Cardiac muscle tissue: occurs only in the walls of the heart
3- Smooth muscle tissue: in the walls of hollow organs. Cells lack striations
188
Skeletal muscle:
Has a nerve and a blood supply.
neuromuscular junction: Where nerve contacts the muscle
Origin on bone is at less movable attachment
Insertion is on more movable attachment
Origin and insertions are by tendon or aponeurosis
189
Motor unit
Motor unit recruitment is the progressive activation of a muscle by successive recruitment of contractile units (motor units) to accomplish increasing gradations of contractile strength.
A motor unit consists of one motor neuron and all of the muscle fibers it contracts.
190
Characteristics of the skeletal muscle:
The skeletal muscle cells are called: fibers
Fibers are long (10-100µm in diameter and several cm long) and cylindrical
Cells are multinucleate, nuclei are peripherally located
Plasma membrane is called a sarcolemma
Cytoplasm is called sarcoplasm
Contain Myofibrils: myofibrils are long rods within cytoplasm, responsible
for striations of the skeletal muscle
A myofibril is a long row of repeating segments called sarcomeres.
191
Sarcomere:
Is the basic unit of contraction of skeletal muscle from one Z line to the next.
Z disc (Z line): boundaries of each sarcomere
Thin (actin) filaments: extend from Z disc toward the center of the sarcomere
Thick (myosin) filaments: located in the center of the sarcomere
Overlap inner ends of the thin filaments contain ATPase enzymes
A bands: full length of the thick filament, includes inner end of thin filaments
H zone: center part of A band where no thin filaments occur
M line: in center of H zone, contains tiny rods that hold thick filaments together
I band: region with only thin filaments, lies within two adjacent sarcomeres
192
Muscle contraction:
when a nerve cell stimulates a muscle fiber, it sets up an impulse in the
Sarcolemma that signals the Sarcoplasmic reticulum to release Calcium ions.
Released Ca++ diffuses through cytoplasm and triggers the sliding filament
mechanism.
Impulses further conducted by t tubules (deep invaginations of the sarcolemma)
193
Mechanism of contraction:
Sliding filament theory:
```
Myosin heads attach to actin
in the thin filaments
Then pivot to pull thin filaments
inward toward the center of the
sarcomere
```
Contraction mechanism is activated
by binding of Ca++ to the thin
filaments and powered by ATP.
194
Thin Filament: Troponin
*A complex of 3 subunits: TnI, TnC, TnT
Troponin has 3 subunits that together form a complex:
Tn C (troponin C) binds to calcium, initiates muscle contraction
Tn T (troponin T), binds troponin complex to tropomyosin
Tn I (troponin inhibitor), inhibits actin binding to myosin heads in resting muscle
195
The Sliding filament hypothesis is a proposal to explain how a skeletal muscle can contract.
Muscle Contraction:
Innervation of muscle by neurotransmitter ACETYLCHOLINE
Calcium released from sarcoplasmic reticulum (SR) into the cytoplasm
Calcium binds to Troponin – C
This releases Troponin – I from the actin binding site; the actin binding site is exposed
Actin can now bind to myosin
When heads of myosin molecules bind to actin filaments, myosin ATPase is activated
ATP (energy form) is released and induces flexion of the myosin heads
Flexion of myosin heads slides actin filaments towards the A band
Myosin heads detach, reattach to next neighboring actin filament
The thin filaments slide in between the thick filaments (muscle contraction).
Mechanism continues until calcium is taken back into the SR
196
Changes in striation during the contraction of skeletal muscle:
Electron micrographs
1- sarcomere that is relaxed
2- sarcomere that is partly contracted
3-sarcomere that is fully contracted
197
Muscle sensors
(know these 4)Types of muscle sensors
Muscle spindles (groups Ia and II afferents) are arranged in parallel with extrafusal fibers.
Golgi tendon organ (group Ib afferents) are arranged in series with extrafusal muscle fibers. They detect muscle tension.
Pacinian corpuscles (group II afferents) are distributed throughout muscle. They detect vibration.
Free nerve endings (group III and IV afferents) detect noxious stimuli.
198
Type of muscle fibers
Extrafusal fibers
- make up the bulk of muscle.
- are innervated by alpha-motoneurons.
- provide the force for muscle contraction.
199
Type of muscle fibers
Intrafusal fibers
- are smaller than extrafusal muscle fibers.
- are innervated by gamma-motoneurons.
- are encapsulated in sheaths to form muscle spindles.
- run in parallel with extrafusal fibers. But not for entire length of the muscle.
200
How the muscle spindle works
Muscle spindle reflexes oppose (correct for) in creases in muscle length (stretch).
- Sensory information about muscle length is received by group Ia (velocity) and group II (static) afferent fibers.
- When a muscle is stretched, the muscle spindle is also stretched, stimulating group Ia and group II afferent fibers.
- Stimulation of group Ia afferents stimulates alpha-motoneurons in the spinal cord. This stimulation in turn causes contraction and shortening of the muscle. Thus, the original stretch is opposed muscle length is maintained.
201
Function of gamma-motoneurons
- innervate intrafusal muscle fibers.
- adjust the sensitivity of the muscle spindle so that it will respond appropriately during muscle contraction.
- alpha-motoneurons and gamma-motoneurons are coactivated so that muscle spindles remain sensitive to changes in muscle length during contraction
202
Smooth muscle:
Cells are spindle-shaped, cells are non-striated and contain no sarcomere.
Separated by endomysium.
Contain one centrally located nucleus.
Grouped into sheets in walls of hollow organs.
e.g.: Walls of circulatory vessels, Respiratory tubes, Digestive tubes
Urinary organs, Reproductive organs, Inside the eye etc.
Are in longitudinal layer or circular layer, both layers participate in contraction .
Contraction: Extracellular Ca++ diffusing into the smooth muscle cell is responsible for sustained contractions. Opening of ca++ channels is graded by the amount of depolarization, the greater the depolarization, the more Ca++ will enter the cell and the stronger will be the smooth muscle contraction. Ca++ combines with a protein , calmodulin, the calmodulin-Ca++ combines with and activates myosin light-chain kinase, an enzyme that catalyzes the phosphorylation of myosin light chains, then it binds to actin and thereby produce a contraction.
Relaxation of the smooth muscle follows the closing of the Ca++ channels.
203
Disorders of muscles:
Muscular dystrophy:
A group of inherited muscle degenerating disease appearing in childhood.
The affected muscles enlarge with fat and connective tissue but the muscle
fibers actually degenerate
204
Disorders of muscles:
Duchenne muscular dystrophy
Sex-linked recessive inherited disease, males are most exclusively affected,
1/3500 boys, diagnosed between age 2-10, muscle weakens, first pelvic
muscles affected, then muscles of shoulder and head, rarely live over 20 years.
Fibers lack a submembrane protein called dystrophin.
205
Disorders of muscles:
Myotonic dystrophy
Chromosome 19 is impacted
Myotonic dystrophy is an inherited disorder in which the muscles contract but have decreasing power to relax. With this condition, the muscles also become weak and waste away. Myotonic dystrophy can cause mental deficiency, hair loss and cataracts.
Onset of this rare disorder commonly occurs during young adulthood. However, it can occur at any age and is extremely variable in degree of severity.
The myotonic dystrophy gene, found on chromosome 19, codes for a protein kinase that is found in skeletal muscle, where it likely plays a regulatory role.
206
The middle ear is connected to meningeal layer.
Any infection(bacterial, viral) in middle ear then patient has risks for bacterial or viral meningitis
207
After depolarization of hair cells the hair cell releases stimulatory neurotransmitter which stimulates the first group of neurons of cochlear nerve which travel to spinal ganglion. First group of nerves synapses with next group of neurons. Second group of neurons travel to medulla oblongata ventral/ dorsal nuclei for cochlear nerve where they synapse with next group of neurons. Third group of neurons, some travel to contralateral stations in contralateral temporal lobe. The next group of neurons(ipsilateral) pass through pons through the lateral lemniscus tract. Then they travel from pons to midbrain. In midbrain the Superior and Inferior Colliculi. Then they synapse with next neuron which then travels to medial geniculate nucleus to synapse with next group of neurons. This neuron travels to superior gyrus of temporal lobe of brain. Specifically area 41 and 42(primary auditory area).
After depolarization of hair cells the hair cell releases stimulatory neurotransmitter which stimulates the first group of neurons of cochlear nerve which travel to spinal ganglion. First group of nerves synapses with next group of neurons. Second group of neurons travel to medulla oblongata ventral/ dorsal nuclei for cochlear nerve where they synapse with next group of neurons. Third group of neurons, some travel to contralateral stations in contralateral temporal lobe. The next group of neurons(ipsilateral) pass through pons through the lateral lemniscus tract. Then they travel from pons to midbrain. In midbrain the Superior and Inferior Colliculi. Then they synapse with next neuron which then travels to medial geniculate nucleus to synapse with next group of neurons. This neuron travels to superior gyrus of temporal lobe of brain. Specifically area 41 and 42(primary auditory area).
208
Vestibular system is formed by 3 semi circles
| superior, inferior lateral or anterior, posterior horizontal
Vestibular system is formed by 3 semi circles
superior, inferior lateral or anterior, posterior horizontal
At the base of semicircular canal there is a dilated part which is called the ampulla(number 3). After ampulla number 14 and 4(utricule then sacule) are the dilated portion which contain the hair cells. The semicircular canal has 2 layers. External layer is bone containing perilymph. Internal layer is thin membrane(blue color) containing endolymph.
Ampulla, Utricle, and Sacule contain hair cells. These hair cells are covered by a gelatinous substance called cupula. At the top of the capula there is another membrane called statoconia.
Semicircular canals detect angular acceleration
209
Semicircular canals detect angular acceleration
Utricle and Saccule detect linear acceleration
Semicircular canals detect angular acceleration
Utricle and Saccule detect linear acceleration
210
Detection of linear acceleration by Utricle and Saccule
when the body is suddenly thrust forward it means that the kind of acceleration by body position
Statoconia has greater mass and heavier than cupula and hair cell
therefore the statoconia falls backwards which leads to stimulation of hair cells
this means the stereocilia moves against the kinocilium which leads to hyperpolarization
when stereocilia bend towards the kinocilium this leads to depolarization of hair cells
after depolarization of hair cells then it leads to opening of Ca2+ channels
Ca2+ enters into cell which leads to releasing of stimulatory neurotransmitter which stimulates the first group of neurons of vestibular nerve
the afferent fiber of vestibular nerve takes the information to CNS then it stimulates the motor system which control the upper and lower limb
the motor system maintains the equilibrium of the body
when equilibrium is achieved the statoconia comes back to resting position which inhibits the stimulation of hair cell
in this condition the body maintains the equilibrium
211
Detection of angular acceleration by semicircular canals
Angular acceleration = semicircular canals
Person turns head from left side to right side
the endolymph which exist in semicircular canal moves to left side
the endolymph which moves to left side pushes back the cupula and cupula moves to left side
by movement of cupula then we have stimulation of hair cells which leads to depolarization of hair cells and stimulation of neurotransmitter which stimulates afferent fiber of neuron
when the afferent fiber takes the information to CNS it means that the adaptation is achieved to that position and capula returns to normal position and endolymph moves to right side
by this way endolymph detects angular acceleration and afferent nerve takes information to CNS which can maintain equilibrium
212
After stimulation of hair cells first group of neurons travels to vestibular ganglion. Synapse with 2nd group of neurons.
Vestibular spinal tract stimulates extension of muscles and inhibits flexor muscle
function: facilitates extensor muscle and inhibits flexion of upper and lower limbs
Second stimulus travels to second node then to floccularnodular lobe
inferior lobe of cerebellum
function: controls general movement of body
Reticulo-spinal tract
3rd stimular travels to third nuceli and then to reticular nucleus then back down spinal cord on reticulo-spinal tract
controls alpha moto neuron and gama moto neuron
alpha and gamma control the skeletal muscle contraction
gamma also controls the sensors in skeletal muscle
function: controls alpha and gama moto neurons of skeletal muscle
alpha for contraction
gama for pain, stretching and others
Rubro-spinal tract
facilitates flexor muscle and inhibits extensor muscle
opposite to vestibulo-spinal tract
Some fibers travel to vestibular ganglion then have synapse in vestibular ganglion
then travel to vestibular nuclei after having synapse the next group travels to nuclei for CN 3,4,6
Medial longitudional fasciulus
controls eye movements
function: control eye movement from CN3, 4, 6
Clinical Point
any damage due to head trauma, intracranial hemorrhage, tumor, manipulation of tissue during surgery, or any damage to vestibular system in inner ear or vestibular nerve then it can effect body equilibrium and patient has severe vertigo
After stimulation of hair cells first group of neurons travels to vestibular ganglion. Synapse with 2nd group of neurons.
Vestibular spinal tract stimulates extension of muscles and inhibits flexor muscle
function: facilitates extensor muscle and inhibits flexion of upper and lower limbs
Second stimulus travels to second node then to floccularnodular lobe
inferior lobe of cerebellum
function: controls general movement of body
Reticulo-spinal tract
3rd stimular travels to third nuceli and then to reticular nucleus then back down spinal cord on reticulo-spinal tract
controls alpha moto neuron and gama moto neuron
alpha and gamma control the skeletal muscle contraction
gamma also controls the sensors in skeletal muscle
function: controls alpha and gama moto neurons of skeletal muscle
alpha for contraction
gama for pain, stretching and others
Rubro-spinal tract
facilitates flexor muscle and inhibits extensor muscle
opposite to vestibulo-spinal tract
Some fibers travel to vestibular ganglion then have synapse in vestibular ganglion
then travel to vestibular nuclei after having synapse the next group travels to nuclei for CN 3,4,6
Medial longitudional fasciulus
controls eye movements
function: control eye movement from CN3, 4, 6
Clinical Point
any damage due to head trauma, intracranial hemorrhage, tumor, manipulation of tissue during surgery, or any damage to vestibular system in inner ear or vestibular nerve then it can effect body equilibrium and patient has severe vertigo
213
Phisiologic nystagmus
| after spinning/dancing eyes may continue to move for a little which will correct itself
Phisiologic nystagmus
| after spinning/dancing eyes may continue to move for a little which will correct itself
214
```
Clinical point
causes
pregnancy due to hormonal change and early morning sickness
progesterone increases
damage to vestibular system or tract(pathway)
hypertension
hypotension
hypercholesterolemia
hypocholesterolemia
endocrine hormone disorder
severe infection in middle or inner ear by bacteria or virus
hypoglycemia
head trauma
tumor
intercranial hemorrhage
```
```
Clinical point
causes
pregnancy due to hormonal change and early morning sickness
progesterone increases
damage to vestibular system or tract(pathway)
hypertension
hypotension
hypercholesterolemia
hypocholesterolemia
endocrine hormone disorder
severe infection in middle or inner ear by bacteria or virus
hypoglycemia
head trauma
tumor
intercranial hemorrhage
```
215
Neuron is able to have action potential
receive stimulus from outside source
oxygen and glucose
glucose is best
Neuron is able to have action potential
receive stimulus from outside source
oxygen and glucose
glucose is best
216
Ependymal cells cover internal environment of ventricles
| accelerate the circulation of CSF
Ependymal cells cover internal environment of ventricles
| accelerate the circulation of CSF
217
Clinical point
astrocyte cell proliferation which occupies part of brain tissue inhibits regeneration of axon in CNS
this is why CNS can not regeneration but PNS can
Clinical point
astrocyte cell proliferation which occupies part of brain tissue inhibits regeneration of axon in CNS
this is why CNS can not regeneration but PNS can
218
M.S.
due to damaged myelin sheath
inhibits axon potential in neurons
if phrenic nerve(C3-5) is impacted then diaphragm can not function = death
M.S.
due to damaged myelin sheath
inhibits axon potential in neurons
if phrenic nerve(C3-5) is impacted then diaphragm can not function = death
219
Dopamine deficiency in brain stem – Parkinson
excess = schizophrenia
Deficiency of dopamine in hypothalamus = hyperprolactimenia(infertility)
Seretonin
deficiency = bipolar or depression
Excess NE or E in adrenal medulla = severe hypertension
Histamine
excess = gastritis and gastric ulcer by increasing HCl secretion
Dopamine deficiency in brain stem – Parkinson
excess = schizophrenia
Deficiency of dopamine in hypothalamus = hyperprolactimenia(infertility)
Seretonin
deficiency = bipolar or depression
Excess NE or E in adrenal medulla = severe hypertension
Histamine
excess = gastritis and gastric ulcer by increasing HCl secretion
220
Neuromuscular junction
innervation of muscle fiber by motor nerve
the motor nerve is presynaptic compartment
muscle tissue is postsynaptic compartment
Review steps of NMJ drawing
stimulus -> opening of Ca2+ channels -> Ca2+ enters presynaptic -> exocytosis of Ach into synaptic cleft -> Ach binds to nicotine receptor on post synaptic compartment(muscle fiber) -> after binding of Ach to its receptor then it leads to opening of sodium potassium channels -> leads to depolarization of post synaptic -> after depolarization then it opens Ca2+ channels which enters the cytoplasm but it is not sufficient for muscle contraction -> Ca2+ stimulates the sarcoplasmic reticulum(SR) -> SR releases Ca2+ into cytoplasm -> cytoplasmic microfilaments Actin and Myosin with the troponin complex(Ca2+ binds to troponin C which can allow muscle contraction)
Troponin I – inhibitory
contraction fails
Clinical point
in myocardial infarction Troponin I increases because there are many contractions not strong enough to cause contraction
Neuromuscular junction
innervation of muscle fiber by motor nerve
the motor nerve is presynaptic compartment
muscle tissue is postsynaptic compartment
Review steps of NMJ drawing
stimulus -> opening of Ca2+ channels -> Ca2+ enters presynaptic -> exocytosis of Ach into synaptic cleft -> Ach binds to nicotine receptor on post synaptic compartment(muscle fiber) -> after binding of Ach to its receptor then it leads to opening of sodium potassium channels -> leads to depolarization of post synaptic -> after depolarization then it opens Ca2+ channels which enters the cytoplasm but it is not sufficient for muscle contraction -> Ca2+ stimulates the sarcoplasmic reticulum(SR) -> SR releases Ca2+ into cytoplasm -> cytoplasmic microfilaments Actin and Myosin with the troponin complex(Ca2+ binds to troponin C which can allow muscle contraction)
Troponin I – inhibitory
contraction fails
Clinical point
in myocardial infarction Troponin I increases because there are many contractions not strong enough to cause contraction
221
In skeletal muscle which is controlled by motor nerve there are sensors
By stretching of skeletal muscle fiber(extrafusal fibers) there is also stretching of intrafusal fiber(the sensors for stretch)
two afferent fibers 1a and 2 take the stretching information to dorsal horn of spinal cord and enter sensory portion of spinal cord
tiny interneuron fibers are synapsed with
alpha motor neuron takes stimul and innervates extrafusal fibers
gama motorneuron takes the info back to intrafusal fiber
In skeletal muscle which is controlled by motor nerve there are sensors
By stretching of skeletal muscle fiber(extrafusal fibers) there is also stretching of intrafusal fiber(the sensors for stretch)
two afferent fibers 1a and 2 take the stretching information to dorsal horn of spinal cord and enter sensory portion of spinal cord
tiny interneuron fibers are synapsed with
alpha motor neuron takes stimul and innervates extrafusal fibers
gama motorneuron takes the info back to intrafusal fiber
222
Smooth muscle
Depends on calcium channels and concentration of Ca2+
Smooth muscle in lumen(blood vessels, Gi tract, etc)
Ca2+ is normally 10mg/dL
Hypercalcemia can cause hypertension because of over stimulation of smooth muscle in blood vessels
30mg/dL or above
(Clinical Point)
Relaxation phase after each muscle contraction is by sarcoplasmic reticulum(SR). SR reaccumulates Ca2+ from cytoplasm which decreases the cytoplasmic Ca2+ concentration.
for smooth muscle closure of Ca2+ channels is required
in hypertension and has hypercalcemia then a calcium channel blocker is required to relax the smooth muscle of blood vessels
Depends on calcium channels and concentration of Ca2+
Smooth muscle in lumen(blood vessels, Gi tract, etc)
Ca2+ is normally 10mg/dL
Hypercalcemia can cause hypertension because of over stimulation of smooth muscle in blood vessels
30mg/dL or above
(Clinical Point)
Relaxation phase after each muscle contraction is by sarcoplasmic reticulum(SR). SR reaccumulates Ca2+ from cytoplasm which decreases the cytoplasmic Ca2+ concentration.
for smooth muscle closure of Ca2+ channels is required
in hypertension and has hypercalcemia then a calcium channel blocker is required to relax the smooth muscle of blood vessels
