Monday, 24 December 2012

Nervous System

Central Nervous System

The nervous system consists of two major parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The PNS consists of the peripheral nerves ( nerves which are outside the CNS).

Gross structure of the CNS:

The brain: consists of 3 major parts-
  1. Cerebrum and diencephalon
  2. Brainstem (midbrain, pons, medulla) 
  3. Cerebellum

The brain receives 15% of the output of blood from the heart, is highly sensitive to O2 lack, can autoregulate its blood flow, is 1/50th of the body weight and is located in the cranial cavity. CNS covered by 3 meninges (dura, arachnoid and pia) with CSF between the last 2 membranes; 4 ventricles; Blood brain barrier.

 Cerebrum : is the largest part, is divided by a deep clept (gap)  into right and left cerebral hemispheres. The hemispheres are connected by a mass of nerve fibres called the Corpus Callosum. The outer layers consist of the nerve cell bodies (grey matter)- cerebral cortex which shows lots of folds separated by gaps (sulci or fissures) which give it a large surface area. Each hemisphere is divided into 4 lobes (eg frontal, parietal, temporal and occipital) which are connected by masses of nerve fibres or tracts (white matter). Functions are many, include, memory, thinking, intelligence, sensory perception, control of muscle action.

Frontal lobe: Located in front of the central fissure, motor function (area 4, premotor area, supplementary motor areas- planning and execution of voluntary movements. Also motor speech areas (Broca’s area); also personality, emotional behavior

Temporal lobe: sensory areas (hearing and smelling); also helps in control of emotional behaviour in limbic system and functions of the autonomic nervous system; hippocampus involved in learning and memory; Wernicke’s area involved in language comprehension.

Parietal lobe: has somatosensory areas which are involved in sensory judgement and shapes of objects, spatial awareness 

Occipital lobe: behind the parietal and temporal lobe- sight and perception

pain, temperature, pressure and touch from postcentral area).

The motor area from the right side of the brain controls the left side of the body, similarly the right side of the brain receives sensory info from the left side of the body.i.e each hemisphere controls the contralateral side of the body. Left hemisphere  controls the expressed language, the Right hemisphere is dominant for language intonation and body language and  mathematics functions

Within the cerebral hemispheres there are other areas important in a variety of functions. These areas are groups of cell bodies or nuclei. 1. Basal Ganglia- involved in muscle tone and coordination. The basal ganglia starts and stops movements it also contributes to cognitive (intelligence, knowledge, motor learning) and emotional functions.
Diencephalon consists of the thalamus and the hypothalamus. 2. Thalamus- receives sensory input from skin, gut and sense organs and relays signals to the cerebral cortex and also receives info from the cerebellum and basal ganglia
3. Hypothalamus- located below and in front of Thalamus and above the pituitary gland (major endocrine gland of the body). The functions of the hypothalamus include, control of the autonomic nervous system (ANS), thirst and water balance, body temperature, stress response, sleeping and waking cycles, secretion of hormones and apetite.
Limbic System: group of structures (cingulated gyrus, hippocampus, septum, amygdaloid and anterior nucleui) – imp in the regulation of behaviour and memory
Brainstem: consists of the midbrain, pons and medulla
Midbrain- consists of cell bodies and nerve fibres which act as relay stations for nerve fibres and connect cerebrum with lower part of brain.
Pons- located in fron of the cerebellum, mainly nerve fibres which are on the surface and cell bodies which are deeper; this area acts as relay stations
Medulla- 2.5cm long, grey matter deeper and white matter on outer surface, contains vital centres for controlling the cardiac, respiratory, blood vessels and reflexes for vomiting, coughing, sneezing and swallowing. Lots of nerve fibres cross over (decussate) eg from right side of brain to left side of body.
The brainstem also contains a collection of neurones called the Reticular Formation, which conduct ascending and descending nerve impulses and thus help in voluntary movement and sensory information getting to brain.

Cerebellum: Is located behind the pons and below the cerebrum, has 2 hemispheres, grey matter on surface and white matter deeper. Main function is to coordinate the voluntary muscle movement, posture and balance.

SPINAL CORD

Is the elongated cylindrical part of the CNS, surrounded by the membranes and cerebrospinal fluid. It is approx. 45cm long in an adult and 15-18mm thick. The spinal cord is the nervous link between the brain and the rest of the body. In cross section there is grey matter (cell bodies) in the centre surrounded by white matter (nerve fibres).
The grey matter is shaped like and ‘H’ and has cell bodies of sensory cells, lower motor neurones and connector neurones. The white matter is arranged in 3 columns or tracts (sensory nerve fibres, motor nerves, connector neurones). The sensory nerves carry info from skin, tendons, muscles and joints, whilst the motor nerves carry efferent info to the skeletal, smooth, cardiac and secretory glands.

Fine Structure of the CNS
The CNS: Contains excitable (neurones- which don’t replicate) and non-excitable cells (cells which do replicate). Three membranes (Dura, Arachnoid and Pia mater) cover the CNS. The brain contains cavaties (ventricles), containing cerebrospinal fluid (CSF).

Nerve cells or neurones:
 The neurones consist of a cell body, one axon and dendrites. The cell bodies make up the grey matter, the axons and dendrites make up the white matter. Neurones can be sensory (afferent) or motor (efferent) and communicate between nerves by a synapse and chemical neurotransmitter.
Cell bodies: Groups of cell bodies are called nuclei in CNS, and ganglia in PNS, they are also found in the spinal cord.
Axons: Are found in groups called tracts in the CNS; bundles of axons are called nerves outside the CNS, which can be myelinated or non-myelinated
Dendrites: short processes, like branching axons, can be synapses or sensory receptors

Non- Excitable cells:
Four types are found in the CNS which make up to a ¼ to a ½ of the volume of brain tissue. These are Astrocytes, Oligodendrocytes, Microglia and Ependymal cells.
The Astrocytes are star shaped with branching processes which wrap around blood vessels, thus forming  the blood brain barrier. The blood brain barrier, separates the neurones from the blood, protects the brain from toxic substances, but does allow lipid soluble substances through (eg glucose, alcohol, O2, CO2).
Oligodendrocytes are found around nerve cell bodies and axons and form and maintain the myelin sheath (same as schwann cells).
Microglia- found around blood vessels and involved in phagocytic, inflammatory and cell destruction functions
Ependymal Cells- Form the epithelial linings of the ventricles of the brain and the central canal of the spinal cord

Meninges (membranes)- 3 membranes cover the brain and spinal cord. An outer Dura mater, a middle Arachnoid mater and an inner Pia mater. Between the Arachnoid and the Pia is the subarachnoid space which contains CSF. The Dura consists of 2 dense fibrous layers, an inner layer protects the brain and and outer layer lines the inner surface of the skull. The inner layer extends into the spinal cord  and is separated from the vertebrae by the epidural space. The Pia mater is fine connective tissue with minute blood vessels adhering to the brain.

Cavaties (ventricles):- In the brain are 4 cavaties or ventricles containing CSF. The Right, left, 3rd and 4th .

CSF- Is a clear, slightly alkaline fluid, which is secreted continuously (0.5ml/min) into the ventricles by choroids plexuses or vascular areas. Approx. volume around brain and spinal cord is 120mls. It is similar to plasma, but has very little protein. Its functions include: supporting and protecting brain and spinal cord, maintaining uniform pressure, cushions brain and acts as shock absorber, keeps CNS moist and allows exchange between it and nerves.


Peripheral Nervous System



The peripheral nervous system (PNS) consists of  the nerves outside the CNS. Nerves consist of cell bodies, axons and dendrites. The nerves can also be split into myelinated and non-myelinated. Where the myelinated are mainly larger peripheral fibres surrounded by a myelin sheath (formed by Schwann cells). Between these cells are Nodes of Ranvier which help in rapid nerve transmission. These nerves can be split into the motor division and sensory division. The motor division can be further split into the voluntary nerves and the involuntary nerves (ANS).

The nerves of the PNS consists of  31 pairs of spinal nerves, 12 pairs of cranial nerves and a large number of ANS nerves. The spinal nerves are named according to the the vertebral location. They arise from both sides of the spinal cord. There are 8 cervical, 12 thoracic, 5 lumber, 5 sacral and 1 coccygeal.
There are 12 pairs of cranial nerves which can be sensory, motor or mixed.
Sensory – egs I (smell),II (sight), VIII (hearing); Motor- III, IV (move eye muscles), XII (swallowing, speech); Mixed- VII (taste, expressions), X(wide functions- called the vagus).

Spinal Reflexes: Are reflexes which are independent of the brain. A spinal reflex consists usually of 3 parts, a sensory neurone, a connector neurone in the spinal cord and a lower motor neurone. An example of this would be a withdrawal reflex due to a painful stimulus. So a toe or finger which touched a painful stimulus, would stimulate a sensory receptor, sending signals up a sensory afferent nerve, which would synapse with a connector interneurone in the grey matter, which would then synapse with a motor efferent neurone which would send signals to a neuromuscular or neuroeffector junction causing the muscle to flex and thus withdraw the finger or toe.

But the simplest reflex which only involves 2 neurones i.e without a connector neurone is called a monosynaptic reflex eg. Knee jerk. This reflex protects against excessive joint movement. It can be demonstrated at any point where a stretched tendon crosses a joint.
 

 Nerve and Nerve transport


Structure:
Neurones = Nerve cell body+ axon + dendrites.
Bundles of axons make up a nerve fibre.
Bundles of nerve fibres are enclosed by a coat of connective tissue called the Perineurium.
Nerve fibres can be split into Myelinated and Non-Myelinated types. Both have an outer membrane called the Neurilemma (which is the outer layer of the Schwann cells). Most nerves are myelinated. The myelinated nerve has an axon covered by a lipid protein layer called Myelin (secreted by the Schwann cells) which in turn is enclosed by the Neurilemma. At regular intervals along the axon there are gaps or interuptions to the myelin sheath, called the Nodes of Ranvier at which fast nerve transport occurs. The non-myelinated nerve fibre has a Neurilemma and an axon. These are small fibres with diameter less than 1 micrometers. Nerve fibres could also be classified based on size, 3 groups are used (A,B,C). Where ‘A’ are myelinated and large (15-20micrometres) and have fast conduction (100 m/s), ‘B’ are preganglionic autonomic fibres, intermediate in size and ‘C’ are Non-myelinated fibres with the smallest diameter(less than 1.2 micrometres)  and low speed (1-3m/s).

Nerve Impulses:
A nerve fibre conducts nerve impulses (action potential or wave of depolarization) produced by a stimulus. A semipermeable membrane, ion channels and the concentration of ions and proteins on either side of the membrane of excitable cells determine the resting and active state of nerve cells.
Resting Membrane Potential:
Is approximately -70mV for a nerve, with the inside (intracellular) being negative to the outside (extracellular). This is due to concentration and electrical gradients produced across the semi permeable membranes. The inside of the neurone contains high concentration of  K+ ions and proteins with negative charges. The outside contains high Na+ and Cl- ions. Thus the diffusion for K+ is from inside to outside and that for Na+ is from Outside to inside.There is also a Na+/K+ pump in the membrane wall which throws out 3 Na+ for every 2 K+ that enter and uses 1 ATP. This pump is important in keeping the resting membrane constant. Any decrease in  Oxygen or blockage of this pump will damage the cells. An electrical potential opposes the concentration gradient of K+ leaving the cell, also maintaining the resting potential.
Action Potential:
Since the membrane becomes permeable to Na+ ions, then further and further entry of Na+ causes an action potential (+40mV), with the inside now positive and the outside negative. You have to cross a threshold potential to produce an action potential i.e all or none principal. Depolarisation is making the axon more unstable and is caused by Na+ entry into the inside of the cell. Repolarisation is making the axon more stable by entry of K+ ions to re-establish the resting membrane. Hyperpolarisation is making the axon very stable (inside more negative than normal).

Nerve Cell Action Potentials:
The nerve cell synapses with other nerves and dendrites. These can produce both excitatory and inhibitory nerve action potentials. Such as Excitatory post synaptic potentials (EPSP) and inhibitory post synaptic potentials (IPSP). The mechanism of action potential generation is the same as in the axons. This action potential can be modified by presynaptic inhibition and postsynaptic inhibition. Also excitation can be graded and the final output depends on size and number of impulses.
Transport of the nerve impulse:
The nerve impulse can be transmitted both electrically and chemically. A third type of nerve transport is Axosplasmic flow which is transport of substances such as hormones down the nerve (egs neuropeptides synthesized in the cell bodies of neurones in hypothalamus and then transported along the axon to the posterior pituitary).
Electrical transport:
Making a part of the nerve membrane unstable by entry of Na+ ions leads to depolarization (starting an action potential) or instability of the membrane. Returning the membrane to its resting state by return of K+ ions  is called repolarization. The refractory period is the period in which no stimulus can start an action potential.
The conduction velocity is proportional to the size of the nerve. Faster transport in bigger nerves. Also myelinated nerves conduct faster, due to jumps at Nodes of Ranvier, without the leakage found in non-myelinated nerves.

Synaptic Transmission:Can be chemical or electrical.
Electrical Synapses such as gap junctions are low resistance pathways which connect the cytoplasm of adjacent cells. They exchange ions and small molecules across a tiny gap of only 3nanometres, so transport is extremely fast. These gaps are found in cardiac cells, smooth muscle and liver cells.
Chemical synapses have larger gaps (30 nanometres) than electrical synapses. They consist of a presynaptic terminal, a synaptic cleft and a postsynaptic membrane and receptors. Synapses are found between nerves (axoaxonal), between nerves and dendrites (axodendritic), between axons and nerve cell body (axosomatic)  and between nerves and muscle end plates (on muscle fibres). Each neurone in the CNS is in contact with 100,000 presynaptic axon terminals.
The synaptic stimulation can be modified into 2 types:
Spatial summation- inputs from several axons arrive simultaneously at same postsynaptic membrane, these are then added to get the final signal.
Temporal summation- successive stimulation by signals coming one after the other leading to final signal which starts action potential. The chemical transmitter crossing the synapse varies. They can be excitatory such as Glutamate and Aspartate in brain and spinal cord or they can be inhibitory such as Gabba Amino Butyric Acid (GABA) and Glycine  in brain and spinal cord. Other neurotransmitters include dopamine, Noradrenaline and Adrenaline in the sympathetic and CNS. Serotonin in the midbrain. Acetylcholine in the CNS and all motor neurones, and all preganglionic neurones  of autonomic nervous system and postganglionic parasympathetic nerves of the autonomic nervous system.

Chemical neurotransmitter crosses the synapse and then starts another action potential. These action potentials can be excitatory (EPSP= excitatory postsynaptic potential) or inhibitory (IPSP=inhibitory postsynaptic potential).

Neuromuscular transmission occurs as follows:
When a motor neurone comes in contact with muscle fibres, a neuromuscular junction is present.Nerve impulse travels along the motor nerve and causes calcium to be released into the axon ending, this causes vesicles containing the neurotransmitter Acetylcholine (Ach) to fuse with the membrane of the axon ending and release the Ach (process called exocytosis) into the synapse, which then travels across and stimulates the muscle end plate to depolarize  and start a muscle action potential, this leads to calcium release which causes the muscle fibres to contract.
Factors which affect the above mechanisms include,
Not producing enough Ach, blocking or breaking down of Ach, neuromuscular blocking agents such as Curare (blocks Ach at muscle end plate- so muscle can’t contract), Hexamethonium (which blocks Ach at autonomic ganglia) and Atropine (blocks the Ach at heart muscle, thus heart rate goes up, since Ach is inhibitory).

Autonomic Nervous System


The nervous system can be divided into the central (CNS) consisting of the brain and spinal cord and the peripheral consisting of the nerves that are outside the CNS. The peripheral can  be further subdivided into the efferent  nerves which carry signals to the peripheral tissues and the afferant nerves which carry signals back to the CNS. The  nerves can be further subdivided into the somatic nerves (which control voluntary activity such as skeletal muscle contraction and also send sensory information from the periphery such as muscles and skin to the brain) and the autonomic nerves which are involuntary and control the everyday needs of the body.
Autonomic nervous system:
The autonomic nervous system (ANS) coordinates the regulation of a variety of  functions ( egs digestion, movement of food, urination, exercise, blood pressure and blood flow control)  together  with the endocrine system.It is  a major controller of smooth muscle, cardiac muscle and the exocrine glands.

Structure:
It can be split into the 2 divisions of the sympathetic and parasympathetic nervous systems. The efferent motor fibres travel via the spinal cord  and end in organs or ganglia. The afferant fibres travel either directly via the cranial nerves or via the dorsal roots of the spinal cord to the central nervous system.Both divisions are bilateral, and both have 2 neurones between the spinal cord and their effector organs and one synaptic junction before the target organs. Between the 2 neurones is a ganglion (a collection of nerve cell bodies ) . The ganglionic neurotransmitter is Acetylcholine (Ach). Most organs of the body are innervated by both  the parasympathetic and sympathetic but to different degrees. Some organs however only receive innervation from the sympathetic nerves eg adrenal medulla, kidney, pilomotor muscles and sweat glands. The parasympathetic system is normally dominant at rest and when digesting food, whilst the sympathetic is more dominant in activity.

Sympathetic nerves originate from the cell bodies in the thoracic and lumbar spinal cord (T1-L2), then short preganglionic and long postganglionic fibres to finally the organs. They are the most widely distributed. At the organs the sympathetic nerves release the chemical transmitter Noradrenaline.

The parasympathetic nerves arise from the sacral region (S2-S4) of the spinal cord  and the hindbrain and midbrain (cranial nerves), they have a long preganglionic fibre and a short postganglionic fibre. The sacral nerves innervate the blood vessels of the genetalia, bladder and large bowel, whilst the cranial supply the head and viscera. At the organs the parasympathetic nerves release the chemical transmitter Ach.

Control of the heart:
The heart is innervated by  the parasympathetic and sympathetic. Parasympathetic nerves are distributed to the SA and AV nodes and to the atria. Stimulation of these nerves causes a release of Ach which decreases the heart rate and atrial contraction. Sympathetic fibres innervate SA and AV nodes and all the heart muscle. Stimulation causes release of noradrenaline which  increases  heart rate and force of contraction of atria and ventricles.


Nervous control of blood vessels:

Sympathetic  Control:
Is brought about predominantly by sympathetic innervation which is of 2 types, sympathetic adrenergic and sympathetic cholinergic. Sympathetic adrenergic nerves are the majority and are found in most areas of the body, they release Noradrenalin at their nerve endings which stimulate special membrane receptors  to cause vasoconstriction. Their degree of innervation varies e.gs the brain, large arteries and veins and precapillary sphincters are poorly innervated whilst the skin, small arterioles and gut areas are highly innervated.

There are very few sympathetic cholinergic fibres in man, more in other species such as dogs and cats. These fibres innervate precapillary resistance vessels of skeletal muscles. Stimulation of these releases Acetylcholine which causes dilation. Sympathetic cholinergic fibres also innervate the adrenal medulla  and stimulation releases adrenaline and noradrenaline (ratio of 4:1 respectively), and also sweat glands.

Receptors of the sympathetic nervous system-
Are called Adrenergic receptors which are called alpha and beta receptors. These receptors respond differently depending on their location. In general activation of the SNS occurs in activity, stress, trauma, shock etc. and leads to the production of increased blood flow to organs (increased cardiac output) particularly to muscles, increased energy (mainly glucose) and increased release of Noradrenaline and Adrenaline (from the adrenal medulla). Other effects include:

1.      vasoconstriction of blood vessels (eg gut and skin), increased peripheral resistance, increased blood pressure and  dilation of the pupil.
2.      The heart is  activated equally by adrenaline or noradrenaline and leads to tachycardia, and increased force of contraction.
3.      vasodilation of skeletal and coronary vessels,  increased muscle and liver glycogenolysis, increased release of glucagon, relaxation of the uterine smooth muscle and bronchodilation.

Parasympathetic control:
Parasympathetic fibres are not very important to control of blood flow except in the following cases:
i) direct vasodilation, is only really important in genital erectile tissue
ii) Indirect vasodilation, can however be more important for example during exercise. Stimulation of parasympathetic fibres to the salivary, sweat and gastrointestinal glands leads to , which leads to the production of vasodilator substances called Kinnins which bring about vasodilation. e.g. Bradykinin - a powerful vasodilator.
iii) dilates the coronary arteries and face blood vessels.
Receptors of the parasympathetic nerves:
There are 2 types of cholinergic receptors which respond to Ach.
1.      Muscurinic receptors- are mainly found on the organs the heart, smooth muscle and exocrine glands.
2.      Nicotinic receptors- are found in the CNS, adrenal medulla, autonomic ganglia and the neuromuscular junction.
Functions:
Ach causes a decrease in heart rate and cardiac output, decrease in blood pressure, stimulates movement and secretions in the gut, increased secretions and constriction  in the bronchioles, stimulates secretions from the salivary glands and constriction  of the pupil.


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