Lecture+1+Homeostasis+2012 (1)

7/27/2019 Lecture+1+Homeostasis+2012 (1)

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Causes of death in England and Wales 2003

Males No ofdeaths

% of alldeaths

1 Ischaemic heart diseases 54,889 21.62 Cerebrovascular diseases 21,983 8.7

3 MN of trachea, bronchus and lung 17,155 6.8

4 Chronic lower respiratory diseases 14,611 5.8

5 Influenza and pneumonia 13,200 5.2

6 MN of prostate 9,166 3.6

7 MN of colon, sigmoid, rectum and anus 7,480 2.9

8 MN of lymphoid, haematopoietic and relatedtissue

5,878 2.3

9 Aortic aneurysm and dissection 5,403 2.110 Dementia and Alzheimers disease 5,149 2.0

All causes of death 253,852 100.0

Females

1 Ischaemic heart diseases 44,901 15.82 Cerebrovascular diseases 35,825 12.6

3 Influenza and pneumonia 21,277 7.5

4 Dementia and Alzheimers disease13,307 4.75 Chronic lower respiratory diseases 13,294 4.7

6 MN of trachea, bronchus and lung 11,610 4.1

7 MN of breast 11,209 3.9

8 Heart failure and complications and ill-definedheart disease

8,377 2.9

9 MN of colon, sigmoid, rectum and anus 6,571 2.3

10 Diseases of the urinary system 5,157 1.8

All causes of death 284,402 100.0

Circulation related 32.4%

Circulation related 31.3%


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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 effectsdepending on how the receptor is coupled

Total response time seconds to days


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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 responseunless a direct neural connection to the cellexists

Only one type of response, electrical excitation

Total response time < 0.5 seconds


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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


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Langley 1898

the word 'visceral' is unsatisfactory, for theword loses its proper meaning if applied to nervefibres such as those which run to the skin. Inconsequence, it seems to me advisable to adopt

some new term. I propose to substitute the word'autonomic"'. The word implies a certain degreeof independent action, but exercised undercontrol of a higher power. The 'autonomic'nervous system means the nervous system of

the glands and of the involuntary muscle; itgoverns the 'organic' functions of the body.J.Physiol 23 240-270 (1898)


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Peripheral ANS nerves

Somatic motor neurone

Pre-ganglionic ANS

neurone Post-ganglionic ANS

neurone


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Anatomy

of theANS

Sympathetic

outflow, pre-

ganglionic fibres

and ganglia in

red

Parasympathetic

outflow, pre-

ganglionic fibres

and ganglia in

green


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Preganglionic fibres

Small myelinated fibres with an

average diameter of about 2.5mm in

humans

Cholinergic

Nicotinic receptors

ACh

N1

N1N1

N1


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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 whichopens up an ion channel through themembrane.


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Cholinergic Nicotinic

Receptors

Non-specific increase in permeability tosmall cations (reversal potential slightlybelow zero)

Depolarises the post-synaptic

membrane. Local current spread from the

chemically activated region to the axon

Two alpha binding sites 1nm apart atganglion, 2 nm apart at nmj

C6 at ganglion, C10 at nmj,

Why?


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Anatomy

of theANS

Postganlionicfibres

Unmyelinated C

fibres


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Sympathetic Nerves

long postganglionic fibres - spread outover a wide area.

many postganglionic fibres for each pre-

ganglionic (variously estimated at 1:20 toas many as 1:250 in human cervicalsympathetic ganglia)

mainly adrenergic - release noradrenaline

(and NPY).Act on adrenoceptors (a1, a2, b)

a few are cholinergic (muscarinic)


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Parasympathetic Nerves

the post ganglionic fibres tend to be short

highly localised

relatively few postganglionic fibres to eachpre-ganglionic (variously estimated as 1:1

up to 1:10 in human and cat)

cholinergic release acetylcholine (and VIP) act on muscarinic receptors


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Muscarinic

Receptors

Higher affinity

than nicotinic.

Stimulatedby

muscarine.

Blocked byatropine.


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Adrenoceptors

Stimulated by nor-adrenaline/adrenaline

Blocking depends on receptor type:

b1 blocker atenolol

b2 blocker butoxamine

a1 blocker prazosin

a2 blocker yohimbine

General a- blocker - ergot But also causes intense

vasoconstriction and uterine muscle contraction.


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ERGOT (a-antagonist)


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Other transmitters

Adrenergic

nor-adrenaline, Neuropeptide-Y (NPY) andprobably 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


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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


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The sympathetic system is quite

different.

Sympathetic tone esp. nerve supply to thesmooth muscle of the blood vessels -continuous (variable) activity.

Reflex responses to signals from importantcentral receptor systems.

Not specific anatomical targets

No fixed efferent limb output varied in aphysiological context

Specific but not stereotyped?


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A couple of important add-ons

Cholinergic sympathetic fibres in the limbs

The adrenal medullaPre-

ganglionicsympathetic

fibre of

splanchnic

nerve

Modified post-ganglionic cell,

secretes adrenaline and nor-

adrenaline (and NPY) contained

in vesicles Adrenal

cortex

Ch li i S th ti


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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 tospread 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.


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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 ofheart

Can alter renal excretion of salt and water


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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


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The Roles of the Circulation

Respiration

Nutrition

Excretion

Homeostasis (regulation of the constancy of themilieu interieur of Claude Bernard)

Thermoregulation

Defence

Reproduction

Communication (e.g. endocrine regulation)

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Lecture+1+Homeostasis+2012 (1)