AUTONOMIC NERVOUS SYSTEM

ANS

Seminar’s map:

• INTRODUTION• ANATOMIC CONSIDERATIONS• NEUROTRANSMITTERS• RECEPTORS AND BLOCKERS• HIGHER FUNCTIONS• CLINICAL CORRELATION

HORNER'S SYNDROME•NEUROMUSCULAR JUNCTION DISEASES:

MYASTHENIA GRAVIS(MG)LAMBERT-EATON SYNDROME (LES)

: DEFINITION• ANS is the part of the nervous system that

regulates and controls the glands ,muscles and organs throughout the body.

• Operates via subconscious controls .

• SYNONYMS :• Visceral motor system• Involuntary nervous system

Functions:

ANS is responsible for :Rhythm of the heart .Operation of sweat glands.Involuntary muscle movements .Controls the visceral functions of the body

entirely or partially .• i.e. homeostasis except skeletal muscle

contraction .• NOTE: ANS feeds input to CNS .

ANS divisions

• Sympathetic :

Emergency responses (fight or flight)

• Parasympathetic:

Vegetative functions

e.g. secretions, movement of intestines etc.

Note : there is a great deal of integration between both sympathetic and parasympathetic .

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How the ANS can be activated ?

• Often can be operated by means of visceral reflexes entering autonomic ganglia to brain stem or hypothalamus eliciting appropriate reflex.

• Mainly by centers located in the spinal cord , brain stem and hypothalamus , and also limbic cortex can transmits impulses to the centers and in this way influence ANS .

Effect on Different Organs

• Note: Sympathetic over stimulation results in parasympathetic response .

Anatomic consideration

The outflow

The peripheral part of the sympathetic passes out through thoracic and some lumber spinal nerves (fromT1toL2)

» (Thoraco-lumber)

While parasympathetic passes out through some cranial nerves (X,IX,VII,III) and some sacral spinal nerves (S2-S3andS4)

» (Cranio-sacral)

• The ratio of a preganglionic neuron to postganglionic is about 1:20 for the sympathetic neurons

• AND 1:1 for the parasympathetic neurons• This indicates that the effects of the

sympathetic are generalized while those of the parasympathetic are localized

DIVISIONS

• The preganglionic neurons of the sympathetic are short. They leave the spinal nerve through WRC to synapse in sympathetic ganglia with postganglionic neurons they are longer than the preganglionic neurons

DIVISIONS

• The preganglionic parasympathetic neurons are longer than the postganglionic .The ganglia are found near or within the wall of the target organs

Comparison between the SNS and ANS

SNS• CONSIST OF ONE

NEURON CONNECTS THE CENTRAL PART WITH THE TARGET ORGANS

ANS• TWO NEURONS

CONNECT THE CENTRAL PART WITH THE TARGET ORGANS

• THE TWO NEURONS ARE perganglionic AND postganglionic ARE CONNECT TOGETHER BY GANGLIA

Neurotransmitters

The principal neurotransmitters in autonomic nervous system are:

Acetylcholine . Dopamine . Noradrenaline .

1-ACETYLCHOLINESynthesized :-

In the cell body of cholinergic neurons

Acetyl-CoA Choline

Cholineacetyltransferase

Acetylcholine

ACETYLCHOLINE

Released by : All preganglionic parasmathetic neurons All postganglionic parasympathetic neurons All preganglionic sympathetic neurons Some postganglionic sympathetic

neurons(supplying sweat glands,arterioles of skeletal muscles,pilo-erector muscles )

Where does it go ?

At the synaptic cleft , ACH action terminate by the enzyme

acetylecholinestrase .

2 -NORADRENALINE

• released by post ganglionic sympathetic

neurons & adrenal medulla

• synthesized in the cell body of nor-adrenargic neurons.

Steps of synthesis

WHERE DOES IT GO!?

There is no enzyme for its hydrolysis in the cleft.

Into the plasma it hydrolyzed by two enzymes

1 -monoamin-oxidase (MAO)

2 -CATECHOL-O-METHYLE-TRANSFERRASE

The most important metabolite is the VMA which is excreted in urine.

-High amount of VMA in urine indicate hyper production of catecholamine (by tumor in the adrenal medulla= pheochromocytoma )

When the transmitter substance binds with the receptor, this causes a conformational change in the

structure of the protein molecule.

Autonomic receptors

• Cholinergic• Adrenergic • Dopaminergic

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Cholinergic receptors

Two main types1- Muscarinic receptors

found on target cellsblocked by the Drug:

atropine

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Examples:

• Blocks vagal inhibition to the heart tachycardia,

• Inhibits salivary secretion (premedication in surgery)

• Decreases intestinal motility(treatment of colic)

• Dilates the pupil

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2-Nicotinic receptors

• Found on postganglionic cell in all ANS ganglia

Blocked by the Drug: hexamethonium

Widespread effects

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• Nicotinic receptors

Also found on skeletal muscle neuro-muscular junction

Blocked by Drug: Curare

Produces muscle relaxation

Used as premedication in surgery

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Adrenergic receptors

• Alpha 1, 2• Beta 1, 2• Presence of each type of receptor on

target cell determines the effect of transmitter

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Effects of Alpha receptor stimulation

• Dilation of iris - Alpha 1• Constriction of blood vessels - Alpha 1 & 2 • GIT sphincters contract - Alpha 1• GIT secretion inhibition - Alpha 2 • Urinary bladder constriction of inernal

sphincters - Alpha 1 • Ejaculation - Alpha 1 • Decreased insulin secretion - Alpha 2 • Lipolysis - Alpha 1

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Effects of Beta receptor stimulation

Effects of Beta 1 stimulaion

- Tachycardia

- Myocarial contractility

- Lipolisis

- Renin secretion

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Effects of Beta 2 stimulation

• Coronary dilatation• Vasodilatation in sk musc• Skeletal muscle tremor• Broncho-dilatation• Relaxation of uterus• GIT motility decreases

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Autonomic Receptors Blockers

• DRUGS THAT BLOCK TE ACTION OF CHEMICAL TRANSMITTERS

• Alpha receptor blockers• Nonselective • Phenoxybenzamine (Dibenyline)• Phentolamine (Rogitine)• Dihydroergotamine

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Selective alpha blockers

• Alpha 1• Prozasin (minipress)• Alpha 2• Yohimbin

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Beta receptor blockers

• Nonselective • Propranolol (inderal)

ACTS ON BOTH BETA 1 & 2• Selective Beta receptor

blockers• Beta 1 : atenolol • Beta 2 : butoxamine

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Higher control of autonomic function

• Autonomic Nervous System is an important part of our bodies.

• It regulates many vital function in the body

• like heart rate ,blood pressure, GIT function.

• So we have to know what regulates the Autonomic Nervous System it self?

#Autonomic Nervous System is regulated by higher centre like :Hypothalamus Anterior{parasympathetic} posterior{sympathetic}

Reticular formation of medulla and pons.

Higher control of autonomic function

Limbic System is consists of those parts of the brain which are responsible for instinctive behavior and emotion.

In lower animals this part of the brain represents the largest portion of the cerebral hemispheres.

In humans it is restricted mainly to part around the hilum of the cerebral hemisphere.

Limbic System: Higher control of autonomic function

When the Hypothalamus work with Limbic System this can be explain the causation of abnormal reaction such as Psychosomatic disorders characterized by hyper or hypoactivity of autonomic function peptic ulcer hypertension ulcertive colitis migraine are frequnetly encountered examples of these conditions

Higher control of autonomic function

Hypothalamus it need to work to receive information from CNS and send information to the cerebrum above and to the brain stem below.

As a result it mediates some of the effect of Autonomic Nervous System .

So the Hypothalamus is the head ganglion of Autonomic Nervous System.

Higher control of autonomic function

Horner’s syndromeDefinition:• It is a rare condition resulting from

interruption of cervical preganglionic or postganglionic sympathetic innervation to the face .

Causes:

•Injury to the nerve•Injury to carotid artery.•Apical lung tumor•Surgical trauma at the neck.•Hypothalamic or brain stem lesions.

Symptoms:

•Ptosis (drooping of the upper eyelid)

•Meiosis (contraction of eye pupil )

•Anhydrosis (dryness due loss of sweating )•Enophthalmos (abnormal recession of the eyeball in the orbit )

•Rubar (redness due to vasodilatation)

Treatment :

depending on the treatment of it’s causation.

Myasthenia Gravis• It’s a serious fatal autoimmune neuromuscular

disease . (it can occur at any age).

• Caused by : • antibodies block, alter, or destroy the receptors for

acetylcholine at the neuromuscular junction, which prevents the muscle contraction from occurring.

• These antibodies are produced by the body's own immune system. Myasthenia gravis is an autoimmune disease because the immune system -- which normally protects the body from foreign organisms -- mistakenly attacks itself.

Signs and symptoms(The hallmark of myasthenia gravis is fatigability.)

the first noticeable symptom is weakness of the eye muscles.• asymmetrical ptosis (a drooping of one or both

eyelids)• diplopia (double vision) due to weakness of the

muscles that control eye movements• an unstable or waddling gait, weakness in arms, hands,

fingers, legs, and neck, a change in facial expression• dysphagia (difficulty in swallowing)• shortness of breath and dysarthria (impaired speech,

often nasal due to weakness of the velar muscles).

Treatment:Today, myasthenia gravis can generally be controlled. There are several therapies available to help reduce and improve muscle weakness:

Medication:Acetylcholinesterase inhibitors: neostigmine and pyridostigmine can improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor.

Plasmapheresis and IVIG:

If the myasthenia is serious (myasthenic crisis), plasmapheresis. can be used to remove the putative antibodies from the circulation. Also, intravenous immunoglobulins. (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks.

Surgery:Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential neoplastic effects of the tumor. However, the procedure is more controversial in patients who do not show thymic abnormalities.

Inspiratory muscle therapy:

In patients with generalized MG, there is some evidence that a partial home program including training in diaphragmatic breathing, pursed lip breathing, and interval based IMT may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance.

Lambert-Eaton syndrome

#Definition:• is a rare autoimmune disorder that is characterized by

muscle weakness of the limbs. It is the result of an autoimmune reaction in which antibodies are formed against presynaptic voltage-gated calcium channels.

• Caused by : • LEMS is often associated with lung cancer (50–70%).• LEMS may also be associated with autoimmune diseases,

such as hypothyroidism (an underactive thyroid gland) or diabetes mellitus type 1.

• people with MG without a tumor and people with LEMS without a tumor have similar genetic variations that seem to predispose them to these diseases.

Signs and symptoms• The weakness of LEMS typically involves the legs

and arms.• The proximal muscles (those closest to the trunk)

are predominantly affected; this leads to difficulties climbing stairs and rising from a sitting position.

• Physical exercise and high temperatures can worsen the symptoms. Weakness of the bulbar muscles (supplying the mouth and throat) is occasionally encountered.

• Weakness of the eye muscles is uncommon.• Some may have double vision, drooping of the

eyelids and difficulty swallowing.

Treatment.

• If LEMS is caused by an underlying cancer, treatment of the malignancy usually leads to resolution of the symptoms.

• Treatment usually consists of chemotherapy, with radiation therapy in those with limited disease.

• The three treatment modalities aimed at improving LEMS symptoms directly are improving the neuromuscular conduction and suppression of the immune system.

• Two classes of medication are used to improve neuromuscular transmission. Pyridostigmine decreases the degradation of acetylcholine after release into the synaptic cleft, and thereby improves muscle contraction.

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