Autonomic disorders

Case study-2
Section 2
Pathophysiology
Level 2 – pharm D
2022-2023
 The anatomical differences between the sympathetic and
parasympathetic divisions of the autonomic nervous system
The pathway followed by autonomic nerves involves a chain of two neurons.

 The cell body of the first neuron in the chain lies within the central nervous
system (CNS) but its axon, the preganglionic fiber, synpases outside the CNS.

The vagus nerve, which arises from the cranial outflow, is a major component of
the parasympathetic system and provides innervation to the heart, lungs,
esophagus, stomach, small intestine and upper large intestine.

The innervation supplying the lower parts of the large intestine, reproductive
tissues and urinary system arises from sacral areas of the spinal cord.
 Sympathetic nervous system Parasympathetic nervous
system
Origin of • Preganglionic nerves originate in the thoracic • Preganglionic fibers originate
fibers and lumbar regions of the spinal cord. in the brain and in sacral
regions of the spinal cord
Length • Most of the preganglionic neurons are short • These preganglionic fibers are
of fibers • Postganglionic nerves of the sympathetic long compared to those in the
system are generally long. sympathetic system.
Ganglia • Most preganglionic nerves synapse with cell • These preganglionic fibers’
location bodies of postganglionic neurons in a chain of synapse with the
ganglia lying close to the spinal cord postganglionic neuron usually
(paravertebral ganglia). lies in the tissues innervated.
Notes • Some sympathetic preganglionic fibers synapse in collateral ganglia: the celiac,
superior mesenteric and inferior mesenteric ganglia.
The neurotransmitters in the two divisions of the autonomic
nervous system.

Sympathetic nervous system Parasympathetic nervous system

• The ganglionic transmitter of both divisions of the autonomic nervous system is
acetylcholine (Ach).
• The major postganglionic neurotransmitter of • In the parasympathetic system
the sympathetic nervous system is the postganglionic
norepinephrine (noradrenaline), neurotransmitter is
• But a small number of structures are
innervated by sympathetic, cholinergic fibres. acetylcholine.
• These fibres release acetylcholine and the
structures innervated include the sweat
glands and blood vessels supplying skeletal
muscle.
 Release of Ach in the parasympathetic nervous system.
The parasympathetic transmitter acetylcholine is stored in synaptic vesicles within
the postganglionic nerve ending.

1. Action potential arrives at the parasympathetic nerve terminal.

2. Depolarization of the nerve ending

3. Opening of voltage-gated calcium channels.

4. ↑↑ intracellular calcium stimulates fusion of vesicles with the presynaptic

membrane and acetylcholine release into the synaptic cleft.

5. Acetylcholine diffuses across the cleft to the postsynaptic membrane and binds
with muscarinic receptors
6. The binding leads to to opening of Na+
channels and propagation of the action
potentials in the postsynaptic area.

The remaining acetylcholine will be metabolized

by cholinesterase and, as a result, choline will
be taken back up to the presynaptic area and
acetylcholine is resynthesized and stored in the
synaptic vesicles.

Inactivation of Ach by cholinesterase is

rapid so that Ach activity is short-lived.
 Organophosphorous insecticides = Anticholinesterases

Anticholinesterases (inhibit degradation and metabolism of Ach by

cholinesterase enzyme) function as cholinergic stimulants in the PNS since
they greatly prolong and so increase the actions of endogenous acetylcholine
at muscarinic receptors on the effector tissue.
The insecticide spray can enter the body via the lung by inhalation, swallowing
through the mouse and, if splashed onto bare skin, can be absorbed via the
skin, mucous membranes and eyes.
Both the central and peripheral parts of the nervous systems are affected by
the insecticide, mediated by both muscarinic and nicotinic receptors.
 Action Organ Nervous Trans- Receptor Effect
system part mitter
Intestinal Intestine Parasympathetic Muscarinic • ↑ Motility (diarrhea)
cramps (smooth (M3) • sphincter relaxation

Acetylcholine (prolonged action)

muscles) • ↑ Digestive secretions
Lacrimation Lacrimal Parasympathetic Muscarinic • ↑ watery secretions
gland (eye) (Lacrimation)
Sweating Sweat Sympathetic Muscarinic • ↑ sweat secretions
gland (skin) (Sweating)
Twitching Skeletal Somatic NS Nicotinic • Fasciculation (strong,
muscle (Nm) jerky contractions)
Agitation Brain Central NS Cholinergic • Excitatory effect
• large doses
depression of the
respiratory center
 Action Organ Nervous Trans- Receptor Effect
system part mitter
Muscarinic • Slow heart rate

Acetylcholine (prolonged action)

Inhibitory Heart Parasympathetic
cardiac (SA node, AV (M2) (Bradycardia)
action node, Atria) • Slow conduction through
AV node
• ↓ Atrial contractility
Dyspnea Bronchi Parasympathetic Muscarinic • Bronchoconstriction
(lung smooth (M3) • Increased mucus
muscles) secretions
Drooling Salivary Parasympathetic Muscarinic • ↑ salivary secretions
gland (M3) (Salivation)
(mouth)
 Management of insecticide toxicity
 Remove source of contamination such as clothes
 Breathing support (oxygen, ventilation and secretions removal)
 Pralidoxime === to reactivate cholinesterase activity (this drug must be
given within a short time of exposure to anticholinesterases to avoid aging)
 Organophosphorous antidote
Atropine would be a suitable antagonist to the effects of the
anticholinesterase at muscarinic receptors and reverse the intestinal cramps,
lacrimation, drooling, and sweating since atropine is a muscarinic antagonist.
Except for the action on skeletal muscles (twitching and fasciculations)
= nicotinic not muscarinic action
Cause for needing breathing support

Pulmonary obstruction due to intense bronchoconstriction and

increase in bronchial secretion.

Respiratory center depression in the medulla in case of prolonged

exposure

Reduced respiratory efficiency of the diaphragm and chest wall muscles

due to prolonged action of Ach on skeletal muscle
 Routine eye examination
Dilated pupils and it is difficult to focus on objects.
 Cause:- Mydriatics (relax the sphincter muscle of the iris, dilating the
pupil and allowing visualization of the retina)
 Example:- muscarinic antagonists (Atropine= long-acting , tropicamide =
short-acting (preferred)).
Other actions of atropine:
 Cardiac quickening via an action on the pacemaker of the heart (↑ heart
rate)
 Dryness of the oral mucosa by reducing the secretion of saliva.
 Atropine prolonged systemic actions

 If atropine is administered in large amounts, poisoning occurs; this may be

seen following poisoning by deadly nightshade berries.
 relaxation of smooth muscular spasm in the gastrointestinal tract, gall bladder →→
decreased digestive secretions and motility (constipation)
 relaxation of smooth muscular spasm in the urinary bladder and ureter →→ decreased
urination
Dry as a bone: decreased salivary secretion
 Hot as a furnace: inhibition of sweating
 Blind as a bat: dilation of the pupil and paralysis of the ciliary muscle, which
prevents accommodation
 Mad as a hatter: stimulatory effects in the CNS.