APPP 3: The Autonomic Nervous System

What do the beta receptors do?

- all three increase cyclic AMP, all generally excitatory - B1 = eg found in heart - B2 = eg found in bronchial smooth muscle - B3 = eg found in adipose tissue, bladder. Tissue specific actions: Heart, b-receptor activation increases the influx of calcium across the cell membrane and its sequestration inside the cell - increases force of contraction

Postprandial hypotension?

- another thing that can cause you to get low blood pressure and faint - after meal hypertension, after eating a big meal. - In elderly, diversion of blood to the GI circulation results in an uncompensated loss in blood volume. -

Syncope?

- brief loss of consciousness and postural tone - occurs in 3-4% of people and is the cause of 6% of all hospital admissions Fainting.

M3 receptor?

- found in the bladder smooth muscle, airway smooth muscle, eye. - contraction of the bladder - bronchoconstriction - pupil constriction, ciliary

M2 receptor?

- found in the heart - decreases heart rate.

General Function of the Parasympathetic Division?

- Promotes the conservation and restoration of body energy stores.

Examples of conditions associated with aberrant ANS activity?

- Syncope (fainting) - Dopamine b hydroxylase deficiency

Synapse en passant?

- A lot of the autonomic system, especially on the parasympathetic side is another type of system. - you have a whole bunch of varicosities in the axon that can contain vesicles so they can spread out the release over a larger area, and these are called synpase en passant. - this lets one single effector neuron's axon affect a large area of tissue. - predominant on the sympathetic side. - multiple branches of the autonomic nerve fibers are beaded with enlargements called varicosities that contain synaptic vesicles - One efferent fiber can innervate many effector cells There are various swellings calles varicosities that release neurotransmitter along the length of the axons. They form "synapses en passant".

What kind of neuron system is the ANS?

- ANS is a 2 neuron system in both divisions, the cells of origin lie within the CNS and the synapse occurs in the autonomic ganglia located outside the CNS. - There is one neuron in the central nervous system that we call the pre-ganglionic neuron, and then you have a ganglia that is a synapse and then an effector neuron. - Think of the effector neuron as a motor neuron. It releases a different neurotransmitter, but it is very different to motor neurons. - The effector neuron makes neuro-effector junctions which is the same as a synpase, but now it is onto an organ with the various tissues it innervates. And when neurotransmitter is released and acts on the appropriate receptor you get a change in organ function.

Neurotransmitter and Receptor in Autonomic Ganglia?

- Acetylcholine (ACh) is the neurotransmitter released at all autonomic ganglia (sympathetic and parasympathetic). - ACh activates postsynaptic nicotinic receptors - these receptors differ from skeletal muscle nicotinic receptors with regard to their pharmacology and structure: - Receptors made up of different subunits, acetylcholine binds to the a subunit Don't have to remember whether its the alpha subunit or the beta. Different receptors have different subunits which allow them to have different pharmacology.

Cholinergic Presynaptic Bouton?

- Actycholine is different as a neurotransmitter. - its a rare neurotransmitter in which its action isn't terminated by taking it up into the cell. - it actually is broken down by an enzyme called acetylcholine esterase. - broken down into choline and acetate and choline is taken back up. - then synthesis occurs to recreate acetylcholine and put it back in the vesicle. -makes it more susceptible to drug attacks, can block enzyme.

General Function of the Sympathetic Division?

- Allows the body to respond to stress - a mass sympathetic discharge prepares the body for fight (rage) or flight response.

Blood pressure drops and syncope?

- Cerebral blood pressure is usually 15-20mm less than mean arterial pressure at the aortic arch - A drop of mean blood pressure to less than 70 mm (say 90/50) will cause cerebral BP to drop below 40 mm during diastole, and this will result in syncope - Drugs used to control blood pressure can cause syncope.

Unopposed action?

- Certain organs receive input innervation from one division only. This sometimes causes confusion, if you only have sympathetic innervation how do you make things less activated. - Examples: Vascular tone is increased or decreased by varying activity in the sympathetic division alone, no parasympathetic.

Adrenergic Presynaptic Bouton?

- DO NOT HAVE TO MEMORIZE THE DIAGRAM - the diagram is there to show you that most neurotransmitters have this type of a system where they have release and re-uptake. - Have drugs that affect reuptake pumps, can alter how much noradrenaline stays in the synpase. This is the norm for most neurotransmitters - Bottom chart: But acetylcholine is a little different. Tyrosine is the aa that is derived, LDOPA is the precursor for dopamine that gets converted to noradrenaline, that is why dopamine is sometimes released as well, its a precursor for noradrenaleine. Top chart: don't have to worry about this. What happens to the excess noradreneline is it gets broken down, there are key enzymes. Again have drugs that affect both the enzymes.

Quiz question: Which cranial nerve is associated with baroreceptors and sinus carotid receptors?

- Glossopharyngeal innervates baroreceptors.

5 Muscarinic receptor subtypes?

- M1 to M5. - there are three important ones.

What is the main sympathetic neurotransmitter?

- Noradrenaline is the neurotransmitter released at most sympathetic postganglionic neuroeffector sites

Sympathetic Neurotransmitters and Receptors?

- Now we are going to go through some exceptions of the sympathetic nervous system Top: In most systems you have acetylcholine being released into the affecter neuron at the ganglia. And this acting on a neuronal nicotinic receptor. - In most causes the affector neuron released noradrenaline onto the tissue and that acts on adrenergic receptors. Middle: There is an exception, the sweat gland is sympathetic but it actually has affector neurons that are cholgeneric, meaning they release acteylcholine and they act on a muscarinic receptor. That means that drugs that affect the muscarinic receptor do something strange. Bottom: there is one other exception on the kidney, and this is that on the vasculature of the kidney, in additon to noradrenaline being released, some of the effector neurons also release dopamine, which is a precursor for noradrenaline.

Opposing actions?

- One system trying to increase, the other trying to decrease. - Many organs innervated by ANS receive input from both divisions: "heart, bronchioles, intestines, salivary glands, and bladder" receive dual innervation. Often the effects of each division oppose to each other. - Example: Heart rate is increased by sympathetic division and slowed by para-sympathetic stimulation. - Exception: Salivation is increased by activation of either sympathetic or parasympathetic stimulation. HE LIKES TO WRITE QUESTIONS ON THIS.

Result of Sympathetic Activation?

- heart rate increases - blood pressure rises - blood flow is shunted from skin to skeletal muscles. This is because the receptors in the muscles have a receptor that is activated by epinephrine and that makes them vasodilate. - sweating increases - pupils and bronchioles dilate - digestive functions are decreased

Result of Parasympathetic Activation?

- heart rate is slowed - decreases blood pressure - constricts the pupils - stimulates digestive system activity - promotes emptying of bladder and rectum

Know this table, the affects of the sympathetic and parasympathetic nervous system?

- if you remember rest and digest vs fight and flight makes sense. - bronchioles: need more air to run away, need less air if resting opposed. - Eye: if trying to decide if you are going to fight or run away from enemies want a wide field of vision, want to dialte the pupils as much as you can - GI: only affected by rest and digest, sympathetic has no affect on the release of enzymes - Parasympathetic causes the muscle walls of the GI to relax and the sphincters to contract because you don't want the digestive functions to interfere with your ability to run away. - The muscle of the bladder is relaxed and sphincter is contracted because you don't want to pee yourself when running away. - Salivary gland is example of parallel. Makes sense that the parasympatheic promotes salivation because you get a nice watery saliva for food. You salivate under parasympatic because it is a thick mucousy saliva and that lets your mouth open and close, most of us don't bit people when we fight but animals do. - Spleen contraction with sympathetic, don't want in way when you fight as it is easily ruptured.

Alpha 2?

- inhibits the formation of second messengers. - inhibit adenylyl cyclase

Parasympathetic Neurotransmitters and Receptors?

- it is the same in the ganglia, but the difference is that acetylcholine (ACh) is the neurotransmitter released at all parasympathetic postganglionic neuroeffector sites. - ACh activates postsynaptic muscarinic receptors

Mechanisms of syncope?

- normally occurs because you get up too fast from a seated or lying position = A decrease in systemic blood pressure in the standing position - "orthostatic hypotension" = you can't get enough blood to your brain quickly enough when you go from sitting to standing. - An acute decrease in cardiac output (e.g. arrhythmias). The decrease in cardiac output causes the heart to disfunction and you don't get sufficient blood output, lowers blood output in the brain, and you can faint. - An acute increase in cerebrovascular resistance (atherosclerosis). People who have clogged arteries and lose ability to get blood to the brain.

Vasovagal reflex?

- normally sympathetic tone increases and parasympathetic tone decreases to maintain blood pressure when standing. - The vasovagal reflex 1) increases parasympathetic tone to the SA node of the heart 2) decreases sympathetic tone You can actiavte this reflex by being hit in the vagus nerve in the neck.

The Adrenal Medulla?

- on sympathetic side, no equiv on parasympathetic. - The preganglionic neurons make a synapse in within the adrenal medulla onto the chromaffin cell. - The adrenal medulla is innervated by sympathetic pre-ganglionic fibers that release ACh onto chromaffin cells. - It is the equiavlent of a ganglion, the only difference is the chromaffin cell doesn't have any axons coming off of it. - Chromaffin cells are similar to sympathetic effector neurons, but release epinephrine and small amounts of norepinephrine into the circulation - when sympathetic system kicks in, causes chromaffin cells to release ephephrine to increase sympathetic affects.

What are triggers fo the vasovagal reflex?

- pain - fear (people get so scared they faint) - There are mechanoreceptors in the Viscera and arterial tree in your neck - activation by pressure inhibits vasomotor center, which is maintaining your bp. - e.g. compression of the neck getting hit in the neck - compress carotid baroreceptors, and causes you to faint. - Rapid emptying of a distended bladder can cause you to faint. - Stretching of the gastrointestinal tract - nausea, some people get so nauseated they faint. - Trigeminal neuralgia: Nasty pain condition, most painful thing to have. point source if touched, stabbing electrical pain in face.

Nonadrenergic, Noncholinergic Transmitters?

- there are also some other types of neurotransmitter substances that are "co-released" by effector neurons. - Theses are a few of them listed 1) Sympathetic: neuropeptide Y, galanin, vasoactive intestinal polypeptide, calcitonin gene-related peptide & substance P 2) Parasympathetic: nitric oxide, vasoactive intestinal polypeptide, calcitonin gene-related peptide DON'T HAVE TO KNOW THEM -these neuropeptides can act to enhance the effect of autonomic stimulation - e.g. neuropeptide Y is a vasoconstrictor and is co-released with norepinephrine to increase vasoconstriction.

alpha 1 receptor?

- ↑ 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) IP3-promotes the release of Ca2+ from intracellular stores DAG-activates protein kinase C - The alpha target is to increase calcium, but as a result it is excitation, causes smooth muscles to contract - this is what mediates blood vessel contraction.

Coordination of autonomic function - Example: blood pressure regulation by the baroreceptor reflex?

-baroreceptors sense blood pressure and are found at sites such as the carotid sinus and aortic arch. -signals from baroreceptors sent to the vasomotor center in the medulla oblongata - sympathetic and parasympathetic outflow that is appropriate to counteract the original change in blood pressure.

Dopamine b hydroxylase deficiency?

-deficiency in the enzyme which converts dopamine to norepinephrine -results in progressive sympathetic denervation (lose the sympathetic side of your nervous system, don't respond well to stress) but normal cholinergic innervation. What would you predict the cardiovascular symptoms would be? - Low heart rate - unopposed parasympathetic tone - Low normal BP - Orthostatic hypotension - loss of sympathetic tone

Two branches of the autonomic system?

1) Sympathetic system: responds to stressors in environment or psychological stressors. All cells of origin found in the spinal cord in the thoracic and upper lumbar region. There are a string of ganglia starting with the superior cervical ganglia (the head), all the way down the the paravertabral ganglia near the bottom. These send out axons that run along the spinal cord and go to all the organs that the sympathetic nervous system innervates. 2) Parasympathetic system: Quite a descrete system, runs a huge length, there is all types of ganglia. Really only involves a few cranial nerves a a few nerves in the sacral section of spine. The 3rd, 7th, 9th, and 10th cranial, of those the 10th which is called the vagus nerve is the most important one. Parasympathetic system = vagus nerve. Parasympathetic system is different in its structure anatomically, almost all of the cells of origin are either in the brain stem or down in the sacral roots in the cauda equina. The other different is that instead of having a pearl of ganglia, the ganglia in the parasympathetic system are very close to the tissues that they innervate. The ganglia for the autonomic system contain a synapse.

How? (ways this system can activate a-lot of your body very quickly).

Diffuse activation of multiple body organs all at once (anatomy is set up so you can have a big response): -Sympathetic ganglia are located some distance from their target organs and fibers emanating from one ganglion may diverge and innervate many organs. (located far away so can hit a bunch of organs, then have synapse en passant so can release a whole bunch of neurotransmitters over an organ) -One pre-ganglionic neuron may also synapse with many post-ganglionic neurons. -Sympathetic stimulation of the adrenal medulla releases a hormone (adrenaline or epinephrine) which enters the blood stream and effects many organs and tissues.

How?

Discrete and localized activation of certain target organs: -parasympathetic ganglia are usually located in or near organs innervated by them. -ratio of pre-ganglionic fibers to post-ganglionic fibers is lower than that in sympathetic system. Because you don't need much of an effect, just enough to slow things down where they are involved. - no counterpart to adrenaline release

M1 receptor?

Found in the salivary gland and stomach. Increases saliva

In which tissue are the divisions not in opposition?

Heart, Lungs, Sweat gland

What is the function of the ANS?

Homeostasis

The neurotransmitter released to activate salivary gland is?

Noradrenaline Acetylcholine Dopamine

What two major types of receptors does noradrenaline act on?

Raymond Ahlquist (1948) proposed that catecholamines acted via two principal receptors: 1) Alpha (a) receptors - 2 major subtypes a1, a2 -receptors subtypes have unique pharmacology 2) Beta (b) receptors - 3 major subtypes b1, b2, b3 -receptors have unique pharmacology

The blood vessels are innervated by which division of the ANS?

Sympathetic

Autonomic system?

The autonomic nervous system regulates certain body processes, such as blood pressure and the rate of breathing. This system works automatically (autonomously), without a person's conscious effort.