Nervous System: Divisions and Components

• Different body activities are regulated by the nervous system and the endocrine system
• The nervous system regulates quicker than the endocrine system
• The nervous system controls rapid activities like muscle contraction and gland secretion
• The endocrine system controls body metabolism and is a slow mechanism

Divisions of the Nervous System

• Anatomically, the nervous system divides into the Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Central Nervous System (CNS)

• CNS protects the nervous system with bones and meninges
• CNS consists of the brain and spinal cord

The Brain

• The brain includes two cerebral hemispheres (cerebrum), basal ganglia, thalamus, and hypothalamus
• The brain stem includes the midbrain, pons, and medulla oblongata
• The cerebellum lies posterior to the brain stem

The Spinal Cord

• It lies protected inside the vertebral canal
• The spinal cord divides into 31 segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal
• Each spinal cord segment attaches to a spinal nerve on either side, resulting in 31 pairs of spinal nerves

Peripheral Nervous System (PNS)

• PNS is formed by nerves connecting the CNS to body organs, called peripheral nerves
• PNS anatomically includes 12 pairs of cranial nerves arising from the brain
• PNS anatomically includes 31 pairs of spinal nerves arising from the spinal cord
• PNS functionally includes sensory nerves transmitting sensory impulses to CNS
• PNS functionally includes motor nerves transmitting motor orders from CNS to body organs like muscles and glands
• PNS functionally includes mixed nerves containing both sensory and motor fibers

Motor Functions

• Voluntary motor functions are controlled by the will, like skeletal muscle contraction via somatic motor nerves
• Involuntary motor functions are spontaneous and not controlled by the will, such as smooth muscle contraction, cardiac muscle contraction, and gland secretion
• Peripheral motor nerves controlling involuntary motor functions are called Autonomic Nerves (ANS)

Origin and Distribution of Autonomic Nerves

• Cranial autonomic nerves: 3, 7, 9, and 10
• Thoracolumbar autonomic nerves arise from Lateral Horn Cells (LHCs) of all thoracic and upper 2-4 lumbar segments
• Sacral autonomic nerves arise from LHCs of the second, third and forth sacral segments (S2, S3 and S4)

Characters of the ANS

• Most autonomic organs receive a double supply from both the sympathetic and parasympathetic systems
• Cranial and sacral autonomic fibers have complementary functions and constitute the craniosacral division or Parasympathetic Nervous System (PNS)
• Thoracolumbar fibers have functions opposite to those of the craniosacral division and make up the thoracolumbar division or Sympathetic Nervous System (SNS)
• The sympathetic nervous system’s distribution is wider than the parasympathetic nervous system
• Autonomic fibers from the CNS do not directly reach effector organs; they relay on a second neuron via a synapse before transmitting the impulse

Autonomic Pathway

• An autonomic pathway from the CNS to effector organs consists of preganglionic nerve fibers, autonomic ganglia, and postganglionic nerve fibers
• Preganglionic nerve fibers originate from the CNS and terminate in autonomic ganglia where relay occurs
• Autonomic ganglia facilitate synapse between preganglionic and postganglionic fibers
• Postganglionic nerve fibers arise from autonomic ganglia and terminate on the effector organ

Types of Autonomic Ganglia

• Lateral ganglia: Also known as paravertebral or sympathetic chain ganglia
• Lateral ganglia present on each side of the vertebral column
• The chain is only for the relay of the sympathetic fibers.
• Collateral ganglia: Located near major abdominal arteries like the celiac and superior mesenteric arteries
• Collateral ganglia mainly relay sympathetic signals and parasympathetic signals to a very slight extent
• Terminal ganglia: Present inside the wall of the effector organs
• Terminal ganglia primarily relay parasympathetic signals, with very short postganglionic fibers terminating on effector organ receptors
• Autonomic ganglia are distributing centers as a collection of cell bodies of neurons outside the CNS, serving as relay stations to distribute centers

The Functional Control of ANS

• The functional unit of the nervous system is called 'Reflex Arc', which is an involuntary response to a stimulus
• A reflex arc is composed of a receptor, an afferent neuron, a center, an efferent neuron, and an effector organ
• A receptor is responsible for the perception of a stimulus
• An afferent (sensory) neuron conducts the sensory impulse from the receptor to the integrating center in the CNS
• The center recognizes the stimulus & sends a motor order to the peripheral tissues to counteract the environmental change and produce adjustment (homeostasis)
• The efferent (motor) neuron conducts the impulse from the center to the effector organ (motor order).
• The effector organ produces the response

Sympathetic Nervous System (SNS)

• SNS is the "Emergency System" of the body, preparing the body for "Fight or Flight" responses
• It allows us to be excited, fight, runaway from danger and consume energy

Sympathetic Outflow to Head & Neck

• On the Eye:
• Motor to the dilator pupillae muscle = Mydriasis (pupil dilatation to increase light entering the retina)
• Motor to superior tarsal muscles = Retraction (upper eye lid to increase visual field)
• Motor to retro-ocular (Muller's Muscle) = Exophthalmos (eye ball protrusion)
• Effect on Skin:
• Vasoconstriction (decrease VC of skin BI. V.)
• Secretory to sweat glands (increase sweat secretion)
• Motor to erector pilae muscle(erection of hair in animals)
• Effect on salivary glands:
• Stimulate myoepithelial cells in the wall of salivary acini, which causes squeezing, then trophic salivary secretion is released that has already been stored in the acini (trophic= small in volume/viscid)
• VC to salivary Bl. V.
• Effect on cerebral blood vessels:
• Weak VC of cerebral blood vessels.

Horner’s Syndrome

• Cause: Injury of the sympathetic supply to the head and neck or to the superior Cervical Ganglion (SCG), which is a site of relay.
• Manifestations (Clinical Picture): -On the Eye:
  • Ptosis (drooping of the upper eye lid).
  • Meiosis: Constriction of the pupil
  • Enophthalmos (i.e. Sunken eye).
• On the Skin:
• Anhydrosis (Dry skin due to↓ sweating).
• VD in the skin on the affected sidewarm and red skin.

Sympathetic Outflow to Thoracic Viscera

• On the Heart:
  • Increase all properties of the cardiac muscle: Rhythmicity, Contractility, Excitability & Conductivity
  • VD to the coronaries (indirect effect), via increased metabolism / oxygen consumption
• On the Lungs and Bronchi:
  • Bronchodilatation (increases air entry)
  • Inhibits mucus secretion.
• On the Lungs and Bronchi: VC of pulmonary BI. V.

Sympathetic Supply to Abdominal Viscera

• Both VD and VC to abdominal blood vessels. The VC is more potent.
• Inhibitory to smooth muscles in the wall of the GIT, but motor to sphincters, which results in delayed emptying of GIT.
• On the liver, stimulate glycogenolysis, which results in increased blood glucose level.
• Secretory fibers to suprarenal medulla↑ secretion of catecholamines (CAs) mainly adrenaline they have the same functions as sympathetic stimulation but as hormones.
• On the spleen, to stimulates the smooth muscles in the capsule and trabeculae of the spleen, which squeezes the area, releasing ~ 400 ml blood into circulation.

Suprarenal Gland Role in Sympathetic Response

• The suprarenal gland is only an effector organ as a modified sympathetic ganglion that receives autonomic sympathetic fibers as preganglionic fibers.
• Postganglionic fibers are releasing adrenaline directly into the blood stream as hormones is modified to release secretions (i.e. CAs, mainly adrenaline is considered a hormone).
• The suprarenal gland produces hormones has similar effects as sympathetic stimulation, but is prolonged.
• With sympathetic stimulaton, it augment or magnify the sympathetic response during stressful conditions.

Sympathetic Supply to Pelvic Viscera

• VC of the blood vessels of the pelvic viscera including the erectile tissue of the penis and clitoris producing shrinkage of these organs.
• Inhibition of the smooth muscles of the wall of the large intestine is possible, but motor to the internal anal sphincter is more likely, causing retention of faces.
• Inhibition of the smooth muscles of the wall of the urinary bladder is possible, but motor to the internal urethral sphincter is more likely, causing retention of urine.
• Motor to the smooth muscles of the vas deferens, seminal vesicles, ejaculatory duct/prostate is possible, which includes the ejaculation of semen.
• Impact can be seen on Both motor and inhibitory fibers to the ureters, uterus and fallopian tubes

Sympathetic outflow to the Limbs and Thoracic Wall

• Effects of SNS on Skin:
• VC of skin blood vessels
• Stimulation of sweat secretion.
• Erection of hairs.
• Effects of SNS on Skeletal muscles: (i.e. Orbelli Phenomenon)
• VD of skeletal blood vessels
• Increased force of contraction.
• Delays the onset of fatigue.
• Early recovery from fatigue.

General Effects of SNS include

• Increase visual field
• Increase pumping action of the heart to ↑ blood supply to active organs
• Increase oxygenation of the blood to ↑ oxygen supply to active organs
• Shift of blood from less active areas e.g- the splanchnic circulation and skin to areas of maximum activity e.g. skeletal muscles
• Increase the performance of skeletal muscles

Parasympathetic Nervous System (PNS)

• Functions of the parasympathetic cranial outflow:
  • The Oculomotor nn (3rd cranial nn), causes constriction of the pupil (miosis) / increased lens curvature (accomodation to near vision) -The Facial nn (7th cranial nerve):
  • Vasodilatation of blood vessels of submandibular, sublingual salivary & lacrimal glands+ anterior 2/3 of the tongue
  • Stimulates salivation+lacrimal secretion: profuse & Watery
  • Glossopharyngeal nn (9th cranial nerve).
  • Vasodilatation of blood vessels of parotid salivary glands AND posterior 1/3 of the tongue
  • Stimulates parotid salivary secretion (profuse, watery).
  • Vagus Nerve (10th Cranial nerve):
  • On the heart, it inhibits ALL cardiac properties, heart rate, force of contraction, conduction, excitability, oxygen consumption due to cardiac metabolism. VC to coronary blood vessels.
  • On the lungs, bronchoconstriction causes stimulation of bronchial secretion and VD to pulmonary BI. V.
  • On the GIT: Motor to smooth muscles of the wall of the esophagus, stomach, small intestine and the proximal part of the large intestine; but inhibitory to the sphincters which result in accelerated emptying of GIT. Also, secretory for the gastric glands, liver, pancreas and duodenum +VD to blood vessels of GIT
  • Gall bladder (stimulates motor) inhibits the Oddi Sphincter to enhance evacuation of the GB.

Sacral Parasympathetic

• Parasympathetic sacral outflow (S2, S3, S4):
• Contraction of the smooth m of the wall of urinary bladder results, relaxation of internal urethral sphincter causing micturition
• Contraction of smooth muscle of the wall of rectum and relaxation of internal anal sphincter causing defecation
• Vasodilation of the erectile tissue of the penis and clitoris resulting in erection
• Stimulates seminal and prostatic secretion.

Chemical Transmission in ANS

• Nerve impulses from pre- to postganglionic neurons and to effector organs can’t transmit directly because of no cytoplasmic continuity
• A chemical transmitter is necessary
• There’s 2 types of transmitters: Acetyl Choline (Ach) and Catecholamines (CAs)

Acetylcholine

• It is released by cholinergic fibers, the chemical transmitter
• It’s present inside vesicles in the nerve terminals, released by nerve impulse

Release Sites of Ach (Cholinergic Fibers)

• All fibers arising from the CNS (CENTRAL CHOLINERGIC.)
• All Preganglionic fibers in the ANS: sympathetic/parasympathetic
• Motor nn to skeletal muscles (MEP.)
• Preganglionic sympathetic fibers to adrenal medulla.
• All Parasympathetic Postganglionic nerve fibers.
• Some Postganglionic sympathetic:
• Secretory fibers to sweat glands.
• VD sympathetic fibers.
• Some fibers inside the CNS.

Acetylcholine Biosynthesis

(acetylthiokinase) Acetic acid + ATP + Co A-SH = Acetyl-CoA + ADP +Pi (choline acetylase) Acetyl-CoA + Choline = Acetylcholine + CoA-SH. then it’s Stored inside the vesicles of nerve terminals, and released by nerve impulse.

The Fate of Acetylcholine

• They bind to specific receptors (cholinergic receptors) in effector organs.
• The choline esterase enzyme, rapidly hydrolyzes in to acetic acid + choline
• Choline then becomes reabsorbed by the nerve terminal used for Acetylcholine molecule resynthesis

Types of Cholinesterases

• (1) True cholinesterase (near, at the cholinergic nerve endings)
• (2) Pseudocholinesterses (plasma)

Cholinergic Receptors

• Receptors that bind with acetylcholine, thereby producing effects
• Two main types:
• Muscarinic Receptors (M).
• Nicotinic Receptors (N).

Muscarinic Receptors

• These receptors are present in effector organs receiving all/parasympathetic postganglionic or sympathetic cholinergic fibers
• Muscarine binds and produces effects similar to acetylcholine
• Types are:
• M1 (in the brain) activates PLC (IP3) + DAG, (cytoplasmic, Ca2+)
• M2 (in the heart) decreased AC activity & cAMP
• M4 (in the pancreas) activates PLC (IP3)DAG, (cytoplasmic Ca2+ insulin), pancreatic enzyme secretions.
• M2 & M4 (in smooth muscles)
• M3/M5 the pharmacologic and physiologic effects have not been determined.

Nicotinic Receptors

• Located in postsynaptic neurons of the sympathetic/parasympathetic autonomic ganglia, the MEP (N2 or NM). and cells of adrenal medulla
• Receptor stimulation that stems from stimulation by small doses of nicotine can produce like-acetylcholine effects

Drugs Acting on PSNS

• Parasympatomimetics:
  • Direct: Choline esters: methacholine+carbachol/Alkaloids: pilocarpine+muscarine Cholinesterase inhibitors: Reversible: eserine+prostigmine/Irreversible: organophosphorus insecticides+parathion.
  • Parasympatholytics: -Competitive inhibitors and/or persistent depolarization
  • They work by blocking M receptors is done via atropine/homatropine. Blocks the Ganglion by administering the larg doses of nicotine/hexamethonium
  • Neuromuscular/MEP blockers is by implementing Curare

Catecholamines

• Autonomic fibers are called adrenergic fibers when they secrete catecholamines
• They mainly secrete Noradrenaline (NA)
• Includes adrenaline epinephrine), Noradrenaline (norepinephrine) & Dopamine (chemical transmitter (certainCNSneurons)

Site of Action:

• All sympathetic postganglionic fibers are in the sweat glands.
• Skeletal muscles are in the blood vessels.
• Adrenal gland secretes mainly adrenaline (80%), and noradrenaline (20%).

Between adrenaline and noradrenaline

• Adrenaline (epi) Greater is Activity on the HEART.
• Noradrenaline : Generalized VC increasing BP greater than adrenaline
• Adrenaline : Greater Metabolic stimulate the liver.
• It turns liver glycogen into blood glucose (i.e. glycogenolysis) and increases the metabolic rate.

Catecholamines Biosynthesis

• Catecholamines form in adrenergic neurons and the adrenal medulla, from the amino acid phenylalanine (PA):
• PA hydroxylase (PA —> Tyrosine)
• T hydroxylase (Tyrosine —> DOPA)
• DOPA decarboxylase (DOPA —> Dopamine
• NHT Dopamine —> NA —> A

Methods of Disabling:

• Catecholamines go through Active reuptake. Oxidation w/ MAO (to VMA).
• Orthomethylations(Metanephrin and Normetanephrin

Adrenergic Receptors

• Two kinds of adrenergic receptors, alpha, and beta alpha: stimulation produces excitatory effects( excluding GIT) the alpha receptors: on the vascular- constrict the vascular and bring up the blood pressure- also there alpha present in the eye- constricts the blood pressure
• Beta: : stimulation produces inhibitory effects (excluding HEAR)- increase HEART REATE

Classification of Receptors

• The _receptors are further classified:
• 1 present in postsynaptic neurons.
• 2 present 1+2 receptors in the pre and postsynaptic neurons. _receptors are classified:
  • The __receptor has the the heart are excitatory.
  • Two receptors-in the heart and are excitatory The Dopamine Receptors: D1 D2

Drugs on SNS

• sympathomimetics are Stimulant ganglian- small doses of nicotine -stimulant e.g. noradrenaline and adrenaline -stimulating e.g. adrenaline and isoprenaline -Drugs that will lease CA that will provide tymine ephedrine and amphetamine

• Alpha Methyl P-ty rosine can Drugs synthesized reserpine will effect in the sotrage is not effect the drugs that will synthesized and the Guanithdini effects that will prevent the is not effective in the stimulation

• Drugs can be synthesized through the formation- transmitters is like methyldoopa.

-Alpha Blocked and effect a transmitter

• Beta Repector will Alpha Transmitter with a protal