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Causes of death in England and Wales 2003

Males 1 Ischaemic heart diseases 2 Cerebrovascular diseases 3 MN of trachea, bronchus and lung 4 Chronic lower respiratory diseases 5 Influenza and pneumonia 6 MN of prostate 7 MN of colon, sigmoid, rectum and anus 8 MN of lymphoid, haematopoietic and related tissue 9 Aortic aneurysm and dissection 10 Dementia and Alzheimers disease All causes of death Females 1 Ischaemic heart diseases 2 Cerebrovascular diseases 3 Influenza and pneumonia 4 Dementia and Alzheimers disease 5 Chronic lower respiratory diseases 6 MN of trachea, bronchus and lung 7 MN of breast 8 Heart failure and complications and ill-defined heart disease 9 MN of colon, sigmoid, rectum and anus 10 Diseases of the urinary system All causes of death 44,901 35,825 21,277 13,307 13,294 11,610 11,209 8,377 6,571 5,157 284,402 15.8 12.6 7.5 4.7 4.7 4.1 3.9 2.9 2.3 1.8 100.0 No of deaths 54,889 21,983 17,155 14,611 13,200 9,166 7,480 5,878 5,403 5,149 253,852 % of all deaths 21.6 8.7 6.8 5.8 5.2 3.6 2.9 2.3 2.1 2.0 100.0

Circulation related 32.4%

Circulation related 31.3%

Hormonal mechanisms
Responses graded over wide range Responses relatively slow onset Responses turn off slowly Responses occur in any cell which has an adequate number of receptors Responses vary as the hormone-receptor interaction can produce different effects depending on how the receptor is coupled Total response time seconds to days

Neural mechanisms - somatic


Synapses always reliably transmit Responses occur or they do not Responses rapid onset Responses turn off rapidly Highly localised and precise, no response unless a direct neural connection to the cell exists Only one type of response, electrical excitation Total response time < 0.5 seconds

Internal homeostatic functions


May require rapid onset but sustained response Precision required not the same as with somatic responses This is where the ANS comes in

Autonomic Nervous System


When precise control not needed, or for a more widespread effect, ANS is a more diffuse nervous system Nerve fibres conduct more slowly Peripheral endings release chemicals which diffuse more widely to target cells Not a 1:1 correspondence nerve to target cell No specific synapses at the nerve endings Very different, much slower, receptor responses

Langley 1898
the word 'visceral' is unsatisfactory, for the word loses its proper meaning if applied to nerve fibres such as those which run to the skin. In consequence, it seems to me advisable to adopt some new term. I propose to substitute the word 'autonomic"'. The word implies a certain degree of independent action, but exercised under control of a higher power. The 'autonomic' nervous system means the nervous system of the glands and of the involuntary muscle; it governs the 'organic' functions of the body. J.Physiol 23 240-270 (1898)

Peripheral ANS nerves


Somatic motor neurone

Pre-ganglionic ANS neurone

Post-ganglionic ANS neurone

Anatomy of the ANS


Sympathetic outflow, preganglionic fibres and ganglia in red Parasympathetic outflow, preganglionic fibres and ganglia in green

Preganglionic fibres
Small myelinated fibres with an average diameter of about 2.5mm in humans Cholinergic Nicotinic receptors N1
N1 ACh

N1
N1

Cholinergic Nicotinic Receptors


Transmembrane proteins with five structural components. At the nmj - a2bgd structure (N2) At autonomic ganglia - a2b3 (N1) Bind two ACh in order to be activated undergo a conformational change which opens up an ion channel through the membrane.

Non-specific increase in permeability to small cations (reversal potential slightly below zero) Depolarises the post-synaptic membrane. Local current spread from the chemically activated region to the axon Two alpha binding sites 1nm apart at ganglion, 2 nm apart at nmj C6 at ganglion, C10 at nmj, Why?

Cholinergic Nicotinic Receptors

Anatomy of the ANS


Postganlionic fibres Unmyelinated C fibres <1mm in diameter and conduction speed <1m.sec-1

Sympathetic Nerves
long postganglionic fibres - spread out over a wide area. many postganglionic fibres for each preganglionic (variously estimated at 1:20 to as many as 1:250 in human cervical sympathetic ganglia) mainly adrenergic - release noradrenaline (and NPY).
Act on adrenoceptors (a1, a2, b)

a few are cholinergic (muscarinic)

Parasympathetic Nerves
the post ganglionic fibres tend to be short highly localised relatively few postganglionic fibres to each pre-ganglionic (variously estimated as 1:1 up to 1:10 in human and cat) cholinergic release acetylcholine (and VIP)
act on muscarinic receptors

Muscarinic Receptors
Higher affinity than nicotinic. Stimulated by muscarine. Blocked by atropine.

Adrenoceptors
Stimulated by nor-adrenaline/adrenaline Blocking depends on receptor type:
b1 blocker b2 blocker a1 blocker a2 blocker atenolol butoxamine prazosin yohimbine

General a- blocker - ergot But also causes intense vasoconstriction and uterine muscle contraction.

ERGOT (a-antagonist)

Other transmitters
Adrenergic
nor-adrenaline, Neuropeptide-Y (NPY) and probably adenosine different patterns of stimulation will cause different patterns of transmitter release.

Cholinergic
co-release of V-I-P, vasoactive-intestinal polypeptide. proportion of acetylcholine and V-I-P varies with pattern of firing

Is there a functional as well as an anatomical difference between sympathetic and parasympathetic? Parasympathetic responds only to reflex stimulation. Parasympathetic reflexes well defined anatomically Parasympathetic nerves turn off when they are not in use. Vagal tone is only PNS tone

The sympathetic system is quite different.


Sympathetic tone esp. nerve supply to the smooth muscle of the blood vessels continuous (variable) activity. Reflex responses to signals from important central receptor systems. Not specific anatomical targets No fixed efferent limb output varied in a physiological context

Specific but not stereotyped?

A couple of important add-ons


Cholinergic sympathetic fibres in the limbs The adrenal medulla

Preganglionic sympathetic fibre of splanchnic nerve

Modified post-ganglionic cell, secretes adrenaline and noradrenaline (and NPY) contained in vesicles Adrenal cortex

Cholinergic Sympathetic Fibres


in the limbs there are some postganglionic sympathetic fibres which are cholinergic and end on muscarinic receptors (sweat glands etc) not typical, like sympathetic fibres they tend to spread out a fair bit and be involved in specific but nevertheless widespread responses vasodilator fibres, to special vessels in skeletal muscle, may be involved in a non-specific alerting response at the start of exercise.

The Autonomic nervous system and the circulation


The main efferent limb of all cardiovascular reflexes. Can change resistances and volumes of vessels Can change rate and force of contraction of heart Can alter renal excretion of salt and water

Circulation
Bulk transport Diffusion, limited by distance, gradient and molecular mass Circulation ensures exchange vessels in all tissues provided with nutrients All cells linked via the capillary exchange vessels

The Roles of the Circulation


Respiration Nutrition Excretion Homeostasis (regulation of the constancy of the milieu interieur of Claude Bernard) Thermoregulation Defence Reproduction Communication (e.g. endocrine regulation)