Monday, April 25, 2016

Autonomic Nervous System

There's just one unit that I've been neglecting to blog about, and that's Physiology! I blame the lack of tests for me to stress about... not like I'm complaining ;) (Also the main reason why I'm blogging about Physiology and not finishing up those last few posts about Anatomy is because there are a few things that I want to clear up before I write my next post.)

These first few posts are going to be about the autonomic nervous system and the endocrine (hormonal) system, as they help to regulate many functions in the body (and physiology is all about how things function). In doing so, they maintain "homeostasis," or a stable environment in the body.

These control systems can be spoken about has having sensors, integrators and effectors: the sensor is the bit that notices if something is a bit out of line, the integrator figures out what to do, and the effector gets a response done. For example, an increase in blood pressure is sensed by baroreceptors (pressure receptors) located in the carotid sinus and aortic arch. These send signals to the cardiovascular control centre located in the medulla in the brain, which in turn sends out signals to speed up or slow down the heart, returning blood pressure to normal. The sensors here are the baroreceptors, the integrator is the medulla and the effectors are the nerves going to the heart.

About Nerves...

Nerves can be categorised depending on their direction. Afferent nerves go towards the CNS, whereas efferent nerves go away from the CNS (think of the brain telling efferent nerves to "eff off"). Afferent nerves include sensory nerves, whereas efferent nerves include the somatic and autonomic nervous system. The somatic nervous system covers most stuff that we think of as voluntary, whereas the autonomic nervous system deals with involuntary stuff like heart rate and breathing, and is thus very important for keeping lots of things in our body under control.

A very quick recap of what a neuron is: a neuron is, in short, a nerve cell that "sends messages." It has a cell body, which is where most of its organelles are. It is surrounded by dendrites, which pick up messages from other neurons. Neurons also have a long thin axon through which impulses travel. When the impulse reaches the end, neurotransmitters are released into the gap between the end of one neuron and the dendrites of the next (this gap is also known as a synapse). Many autonomic neurotransmitters, however, are actually released from varicosities (irregular expansions on the axon), which allows for diffuse, non-directional release.

In the autonomic nervous system, the CNS sends out one nerve, which synapses with another, which synapses with the target organ. The bit where autonomic nervous system (hereafter referred to as ANS because I can't be bothered typing it out in full any more) neurons synapse is also known as a ganglia. The first neuron is known as a preganglionic neuron, whereas the neuron afterwards is known as the postganglionic neuron. It sounds somewhat inefficient having two nerves to go to one organ, but in fact this system has advantages as multiple neurons can stimulate one neuron, or vice versa: one neuron can stimulate multiple other neurons.

The autonomic nervous system can also be further categorised into three different divisions: sympathetic, parasympathetic and enteric (gut). I'm only going to cover the first two. They have distinct anatomical and physiological differences. Most organs receive innervation from both systems, though there are some exceptions (for example most blood vessels only receive sympathetic innervation). The two systems also tend to have opposite effects, but not always: both stimulate the secretion of saliva, but the contents of saliva may be different depending on which system has stimulated the secretion. Another common misconception is that only one of these systems is active at a time: in reality, usually both systems are active, though one may predominate depending on what's going on.

Sympathetic Nervous System

Sympathetic nervous system nerves leave from the thoracic and lumbar regions of the spinal cord as white rami (see my anatomy posts for more information). Most of the ganglia lie in a long line known as the sympathetic trunk, located close to the spinal cord. The preganglionic neurons tend to be short, as the sympathetic trunk is not too far away, but the postganglionic neurons are long. The fact that the synapses are pretty much all in the same place may also be the reason why the sympathetic nervous system tends to act pretty much as one unit, but I'm not 100% sure about this.

The sympathetic nervous system is well-known for participating in the "fight-or-flight" response, though it's also pretty important in more mundane things such as making sure that our blood pressure doesn't drop when we get out of bed in the morning. It causes an increased heart rate and cardiac output (which is heart rate multiplied by stroke volume- more on this when I write about the heart later on). It also causes vaso- and venoconstriction (i.e. constriction of arteries and veins). Other effects include the dilation of pupils, opening of respiratory airways, breakdown of glycogen and fat stores to provide energy, increased sweating, redistribution of blood flow away from the digestive and urinary systems and towards the muscles and activation of the adrenal medulla which synthesises hormones which compound the effects of the sympathetic nervous system.

About the adrenal medulla: the medulla is the middle part of the adrenal glands, which are located on top of the kidneys. The adrenal medulla secretes catecholamines, of which there are two main ones you need to know: adrenaline and noradrenaline (a.k.a. epinephrine and norepinephrine). These are released by chromaffin cells, which are stimulated directly by preganglionic neurons in the sympathetic nervous system (there is no postganglionic neuron required here- the chromaffin cell pretty much is the postganglionic cell). Adrenaline and noradrenaline pretty much do the same stuff that the rest of the sympathetic nervous system does (in fact, noradrenaline is a common neurotransmitter used in the sympathetic nervous system, as I'll expand on in a bit).

Now time to talk about neurotransmitters and receptors! All autonomic nervous system preganglionic nerves secrete acetylcholine (ACh), regardless of whether they are part of the sympathetic or parasympathetic nervous system. AcetylCHOLINE is recognised by CHOLINErgic receptors, of which there are two main ones: nicotinic and muscarinic. Pretty much the only ones involved in the sympathetic nervous system are nicotinic receptors, as they're found on postganglionic cell bodies as well as the postsynaptic membranes of skeletal muscle cells. After ACh has done is job, it is rapidly broken down by extracellular acetylcholinesterases.

Postganglionic cells secrete noradrenaline- see, I told you it was commonly used in the sympathetic nervous system! The only exception is sweat glands- the postganglionic cells that innervate sweat glands are also cholinergic. (Chromaffin cells might also be considered an exception as they don't have postganglionic neurons: instead, they are innervated directly by preganglionic cholinergic neurons.) Noradrenaline binds to adrenergic receptors, which also bind adrenaline. There are two types of adrenergic receptors, each with two subtypes. Here are examples of where they are located and what effects they have (bear in mind that this is as far from a conclusive list as you could possibly get- well, without leaving the page blank, of course).
  • alpha 1 receptors are located in the smooth muscle of blood vessels, where they stimulate them to contract.
  • alpha 2 receptors are located in the pancreas, where they inhibit insulin release.
  • beta 1 receptors are located in the heart, where they stimulate the heart to increase the rate and force of contraction. These can be blocked by the drug propranolol.
  • beta 2 receptors are located in the smooth muscle of airways, where they have an inhibitory effect, resulting in relaxation. They have a greater affinity for adrenaline than noradrenaline (all other subtypes have roughly equal affinity for both adrenaline and noradrenaline).
Another important thing to remember is that specific neurotransmitters cannot said to have a certain effect. It's how the signal is transduced by the cell that matters. Here's another way of explaining that that might make more sense: you can't say that "noradrenaline stimulates stuff" because, as I just listed above, it can cause contraction or relaxation, depending on the receptor and target cell.

Before I move on, just a quick word on how the body gets rid of acetylcholine and noradrenaline. They can be taken back up by the sympathetic nerves, where they can be broken down by monoamine oxidase (so I wonder what happens in patients who take MAOIs- monoamine oxidase inhibitors? Hmm...). They can also be inactivated by catechol-O-methyltransferase in the liver.

Parasympathetic Nervous System

The parasympathetic nervous system generally has opposing effects to the sympathetic nervous system. While the former is all about "fight or flight," this system is all about "rest and digest."

Anatomically they are fairly different. Parasympathetic nerve fibres arise from the base of the skull or the sacral region of the spinal cord. Preganglionic neurons don't synapse until they are quite close to their target organs. This is probably why parasympathetic stimulation tends to be more specific.

As I mentioned, all autonomic preganglionic neurons release ACh. Parasympathetic postganglionic neurons also release ACh. Target cells in the parasympathetic system have muscarinic receptors, rather than the nicotinic ones found nearly everywhere else. Muscarinic receptors can be blocked by the drug atropine.

Autonomic Conflict

As I've alluded to previously, the idea that only one of these two systems is active at a time is a myth. In fact, in some cases, both systems can be stimulated simultaneously. An example of this is the dive reflex. When submerged in cold water, the parasympathetic nervous system is activated, slowing down the heart rate so as to conserve oxygen. At the same time, the sympathetic nervous system is activated due to stimulation by temperature receptors. Some people can get arrhythmias (abnormal heart rhythms) by doing this, though, so do be careful if you want to test this. (Oh, and since I've warned you, if you die it's not my fault.)

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