OPT 214

GENERAL PHYSIOLOGY II

OPT 214 – GENERAL PHYSIOLOGY II NOTES

Outline

Neurophysiology Physiology of the sensory and motor systems Muscles and nerves as a functional unit Hormonal and neuro-endocrine regulation Inheritance, Genes and Diseases

Introduction to General Physiology II

The different function of the body organs and systems are regulated by two main regulatory mechanisms:

1- Chemical regulation; by hormones, vitamins, enzymes, ions, gases and chemical transmitters. Chemical regulation is characterized by having a slow onset and prolonged duration of action, chemical regulation controls mainly the metabolic functions of the body.

2- Nervous regulation; by the nervous system. It is characterized by having a rapid onset and a short duration. So, nervous regulation controls the rapid activities of the body.

The two mechanisms are complementary and can therefore influence each other e.g. certain chemical substances can either stimulate or inhibit the nervous system, and in turn influence the nervous regulation. On the other hand, stimulation of the nervous system leads to release of chemical substances e.g. hormones which influence the chemical regulation.

The nervous system performs the following functions:1- Sensory functions: The sensory system receives sensory information from the skin,

deeper tissues (subcutaneous tissues, muscles, joints and bones) viscera and special sense organs (eye, nose, ear and tongue). The sensory stimuli give the brain information about the external and internal environment which help in control of the body functions. When these sensory information reach the central nervous system (CNS), they produce the following:

- Immediate reflex action by sending motor impulses to the muscles or glands.- Perception of the specific sensation.- Stored in the brain in the from of memory (if important) or ignored. The stored

memory help in the process of thinking, learning and speech. Also determines the future response of the body to these stimuli.

2- Motor functions: The nervous system controls: - Voluntary movements, muscle tone and body posture.- Activity of smooth muscles and cardiac muscle.- Secretion of all exocrine glands as well as most of the endocrine glands.- Arterial blood pressure, respiration and body temperature.

3- Higher mental functions: As memory, learning, thinking, emotions, personality character etc.

NEUROPHYSIOLOGY

Outline

Introduction to NeurophysiologyOverview of the Nervous System The Neuron and Synapse

Reference Materials:

INTRODUCTION TO NEUROPHYSIOLOGY

The sensory part of the nervous system plays a great role in the day to day coordination of sensory activities and the initiation of motor responses. it is vital that students should have a general knowledge of the working of the brain in this regard. Likewise, the reticular formation help to awaken animals from states of sleep and makes us to be conscious, therefore a study of it functions

Neurophysiology (from Greek, neuron, "nerve", physis, "nature, origin"; and -logia) is a branch of physiology and neuroscience that is concerned with the study of the functioning of the nervous system.

The primary tools of basic neurophysiological research include electrophysiological recordings, such as patch clamp, voltage clamp, extracellular single-unit recording and recording of local field potentials, as well as some of the methods of calcium imaging, optogenetics, and molecular biology.

Neurophysiology is connected with electrophysiology, neurobiology, psychology, neurology, clinical neurophysiology, neuroanatomy, cognitive science, biophysics, mathematical biology, and other brain sciences.

OVERVIEW OF THE NERVOUS SYSTEM

The nervous system has three main functions:

1. Sensory input, 2. Integration of data, and 3. Motor output.

Sensory input is when the body gathers information or data, by way of neurons, glia and synapses.

The nervous system is composed of excitable nerve cells (neurons) and synapses that form between the neurons and connect them to centers throughout the body or to other neurons.

These neurons operate on excitation or inhibition, and although nerve cells can vary in size and location, their communication with one another determines their function.

These nerves conduct impulses from sensory receptors to the brain and spinal cord. The data is then processed by way of integration of data, which occurs only in the brain.

After the brain has processed the information, impulses are then conducted from the brain and spinal cord to muscles and glands, which is called motor output. Glia cells are found within tissues and are not excitable but help with myelination, ionic regulation and extracellular fluid.

The nervous system is comprised of two major parts, or subdivisions,

1. The Central Nervous System (CNS), and 2. The Peripheral Nervous System (PNS).

The CNS includes the brain and spinal cord. The brain is the body's "control center". The CNS has various centers located within it that carry out the sensory, motor and integration of data. These centers can be subdivided to Lower Centers (including the spinal cord and brain stem) and Higher centers communicating with the brain via effectors.

The PNS is a vast network of spinal and cranial nerves that are linked to the brain and the spinal cord. It contains sensory receptors which help in processing changes in the internal and external environment. This information is sent to the CNS via afferent sensory nerves. The PNS is then subdivided into the autonomic nervous system and the somatic nervous system. The autonomic has involuntary control of internal organs, blood vessels, smooth and cardiac muscles. The somatic has voluntary control of skin, bones, joints, and skeletal muscle.

The two systems function together, by way of nerves from the PNS entering and becoming part of the CNS, and vice versa.

Division of the Nervous System:

I] Central Nervous System (CNS):

It is the part of the nervous system which lies inside the bony cavities (skull and vertebral column). It is divided into

A) Brain; which includes:1. Cerebrum; which consists of:

a. Cerebral cortex.b. Subcortical centers (thalamus, hypothalamus and basal ganglia).

2. Cerebellum.3. Brain stem (mid brain, pons and medulla oblongata).

B) Spinal cord; which is divided into:1. Cervical region (8 segments).2. Thoracic region (12 segments)3. Lumber region (5 segments).4. Sacral region (5 segments).5. Coccygeal region (1 segment)

II] Peripheral Nervous System (PNS):

It includes the different nerves connecting the CNS with the various organs of the body. PNS can be classified by many ways:

A) Anatomical classification: PNS is classified into:

1- Cranial nerves: (connected with brain) there are 12 pairs of cranial nerves.

2- Spinal nerves: (connected with the spinal cord) there are 31 pair of nerve; one pair of nerves arises from each segment of the spinal cord (8 cervical, 12 thoracic, 5 lumber, 5 sacral and one coccygeal spinal nerves).

B) Physiological classification:

The PNS can be classified according to its function into:

I- Somatic nervous system; which supplies the body wall and extremities by:

1) Somatic sensory fibres which carry sensory information to CNS from skin, subcutaneous tissues, skeletal muscles, joints and bones. Their mother cells are present in the dorsal root ganglia (DRG) of the spinal nerves or in similar ganglia of the cranial nerves. Somatic sensory fibres carry:

Cutaneous sensations (cutaneous pain, temperature and touch).

Deep sensation (deep pain, sense of pressure, sense of position, sense of movement, sense of muscle tension and stretch).

Afferent impulses of somatic reflexes.

2) Somatic motor fibres which carry motor orders from CNS to skeletal (voluntary) muscles.

N.B. All spinal nerves that contain both sensory and motor fibres is mixed nerves.

Some cranial nerves are purely sensory (olfactory, optic and auditory nerves), some are purely motor (Oculomotor, Trochlear and Abducent nerves which move the eye). The remaining cranial nerves are mixed nerves.

II- Autonomic (visceral) nervous system (ANS); which supplies the internal organs (the viscera) by:

a. Autonomic sensory (afferent) fibres; which carry sensory information from the internal organs to the CNS. Autonomic sensory fibres carry:

Visceral sensations (visceral pain, desire of micturition and defecation, sense of hunger etc).

Afferent impulses of autonomic reflexes.

b. Autonomic motor (efferent) fibres; that carry motor orders from the CNS to the smooth (involuntary) muscles, cardiac muscle and glands.

NEURONS

The nervous system is composed of:

(1) Neurons (nerve cells): These are the structural and functional units of the nervous system. The human nervous system contains about 1012 (one trillion) neurons.

(2) Neuroglial cells: These cells represent about 10 to 50 times the number of neurons. Neuroglial cells support and protect the neurons.

Classification of neurons:

a) Sensory or afferent neurons, conduct impulses from the sensory receptors to the CNS.

b) Motor or efferent neurons, conduct impulses from the CNS to the effector organs. There are two types of motor neurons:

- Somatic motor neurons, which provide both voluntary and reflex control of skeletal muscles.- Autonomic motor neurons, which innervate the involuntary effector organs (smooth muscles, cardiac muscle and glands).

c) Interneurons (about 99% of all neurons), are located inside the CNS and serve the integrative functions of the nervous system.

Structure of Neurons:

A Typical Neuron

Neurons vary considerably in size and shape according to their sites and functions. In general, they are formed of the cell body and cell processes.

A) The cell body (Soma):

The cell body is the enlarged part of the neuron, which contains the nucleus. It controls the metabolic processes and provides nutrition for the whole neuron. The cell bodies inside the CNS are usually collected into groups called nuclei or centers. The cell bodies in the PNS usually collect to form ganglia. The cell body is surrounded by the cell membrane which continues to cover its processes.

The cell body contains the following:

-Nucleus: The nucleus of the neuron contains one and sometimes two nucleoli, but no centrosome. The absence of centrosomes indicates that the neuron has lost its power of division. The nerve cells once destroyed are replaced by neuroglia.

-Neurofibrils: These fibrils (small fibers) are composed of bundles of neurofilaments. They extend into the processes of the cell. They form the main support of the neuron.

-Microtubules and microfilaments: They are distributed throughout the cytoplasm of the cell body and extend into the axon. They form the main support of the neuron cytoskeleton (in addition to neurofibrils) which supports the neuron and maintains its shape. Microtubules and microfilaments also help in transport of materials and organelles down from the cell body to the axon. Microtubules are thought to form tracks along which organelles are transported.

-Nissl bodies: These are granular materials which are present in the cell body and are not present in the dendrites or axon. Nissl bodies are responsible for protein synthesis.

-Endoplasmic reticulum, - Golgi apparatus., -Mitochondria., - Ribosomes.

B) The cell processes:

1. The Dendrites: are multiple short processes which extend from the cell body. They extend to the surrounding area to act as receptive surfaces. So, the dendrites increase the surface area of the cell body. The receptor surfaces of dendrites collect impulses and transmit them to the cell body.

2. The Axon (Axis Cylinder): is a single longer process that conducts impulses away from the cell body. Axons vary in length from only a millimeter to as long as a meter or more (axons extending from the spinal cord to the foot).

At its distal end the axon divides extensively into thousands of thin branches called axon terminals. These terminals makes junction with one of the following:

a) Dendrites or cell body of another neuron forming a neuro-neural junction or synapse.b) Muscle fibers to form a neuro-muscular junction.c) Secretory gland to from a neuro-epithelial junction.

The Axons are covered by two sheaths:

(1) Myelin (Medullary) Sheath:

All axons more than 1 m in diameter are myelinated. Those of smaller diameter are generally unmyelinated. Myelin is a white, lipid rich substance (lipoprotein complex) which acts as an electric insulator. Myelin sheath is made up of compressed layers of the cell membrane of Schwann cells which make successive wrappings around the axon. Myelin sheath envelops the axon except at its terminal ending. It is not a continuous layer, it is interrupted at intervals of about 0.1 to 1.0 mm by nodes of Ranvier. Through these nodes ions and water can undergo exchange with the surrounding tissues.

Myelin is responsible for the white color of the white matter of the brain and spinal cord. In the CNS, myelin sheaths are formed by oligodendrocytes (a type of neuroglial cells) because Schwann cells are not present inside the CNS.

(2) Cellular Sheath (Sheath of Schwann):

The axons in the PNS are surrounded by a living sheath of Schwann cells known as sheath of Schwann. The outer layer of the Schwann cells is called the neurilemma. Each Schwann cell only wraps about 1 mm of the axon, leaving gaps of exposed axon between the adjacent cells (nodes of Ranvier). Sheath of Schwann is essential for regeneration of the damaged nerve fibers which occurs only in the PNS (Schwann cells are absent in the CNS).

SYNAPSES

Synapse is the site of contact between the axon of a neuron called (pre synaptic neuron) and the cell body of another neuron called (post synaptic neuron) pre-synaptic neuron gives rise to large number of pre-synaptic terminals each of them ends by a swelling known as (synaptic knobs). These knobs are separated from the post synaptic neuron by a narrow space known as (synaptic cleft) synaptic knobs contain vesicles of chemical transmitter.

Synaptic transmission:

It is the process by means of which pre synaptic neuron can excite or inhibit post synaptic neuron.

A) Synaptic Excitation:

It results from stimulation of Excitatory pre-synaptic neuron; this neuron secretes excitatory chemical transmitter from synaptic knobs which may be (Acetylcholine, Noradrenalin or Dopamine). Excitatory chemical transmitter increase the permeability of the membrane to Na+ ions which go inside and produce local depolarization in post synaptic neuron a condition known as Excitatory post-synaptic potential (E.P.S.P).

Properties of E.P.S.P:

1- It is of short duration (15ms) then disappear.

2- It is sub-minimal i.e. does not reach firing level.

3- It is associated with increased excitability i.e. sub-minimal stimulus applied at the same time can produce response.

4- It can be summated by:

Spatial summation: It is produced by stimulation of several numbers of pre-synaptic terminals at the same time.

Temporal summation: It is produced by stimulation of a single pre-synaptic terminal by a several stimuli after each other within a very short time (less than 15 ms) i.e. before disappearance of E.P.S.P.

B) Synaptic Inhibition:

It results from stimulation of inhibitory pre-synaptic neuron. This neuron secretes inhibitory chemical transmitter from synaptic knobs which may be (GABA or A.A. Glycine).

Inhibitory chemical Transmitter increase the permeability of the membrane to K+ ions which go outside and produce local hyper polarization in the post synaptic Neuron, a condition known as inhibitory post-synaptic potential (I.P.S.P).

Properties of I.P.S.P:

- It is of short duration.- It is associated with decreased excitability.- It is sub-minimal and can be summated.

Properties of Synaptic Transmission

(1) One way conduction: Impulses pass from pre synaptic neuron to postsynaptic neuron and not in opposite direction because chemical transmit are present only in pre synaptic neuron.

(2) Synaptic delay: It is the time needed by impulse to pass from pre synaptic neuron to post synaptic neuron. This time is consumed for secretion of chemical transmitter, its diffusion through synaptic cleft and its reaction with the membrane. It is about 0.5 m. sec.

(3) Synaptic fatigue: Repeated stimulation of pre synaptic neuron leads to gradual decrease in the response of the post synaptic neuron. It is due to depletion of chemical transmitter present in the vesicles of the pre synaptic knobs.

(4) Effect of Drugs: Drugs stimulate synaptic transmission e.g. caffeine and strychnine. Drugs inhibit synaptic transmission e.g. Hypnotics, Narcotics & Anesthetics.

(5) Effect of pH: Alkalosis stimulates synaptic transmission e.g. in patient with epileptic focus, alkalosis may produce convulsions as a result of spread of excitation from this focus to other brain centers. Acidosis inhibits synaptic transmission e.g. in patient suffering from acidosis (e.g. diabetic acidosis) they may pass into come due to inhibition of higher centers.

(6) Effect of Hypoxia: Severe Hypoxia (Anoxia) produce marked inhibition of synaptic transmission so decreased blood flow to the brain leads to fainting in less than 5 seconds.

SENSORY AND MOTOR SYSTEM PHYSIOLOGY Introduction Sensory function Motor function Autonomic Nervous System Higher Functions of Nervous System

IntroductionThe nervous system performs the following functions:

4- Sensory functions: The sensory system receives sensory information from the skin, deeper tissues (subcutaneous tissues, muscles, joints and bones) viscera and special sense organs (eye, nose, ear and tongue). The sensory stimuli give the brain information about the external and internal environment which help in control of the body functions. When these sensory information reach the central nervous system (CNS), they produce the following:

- Immediate reflex action by sending motor impulses to the muscles or glands.- Perception of the specific sensation.- Stored in the brain in the form of memory (if important) or ignored. The stored

memory helps in the process of thinking, learning and speech. It also determines the future response of the body to these stimuli.

5- Motor functions: The nervous system controls: - Voluntary movements, muscle tone and body posture.- Activity of smooth muscles and cardiac muscle.- Secretion of all exocrine glands as well as most of the endocrine glands.- Arterial blood pressure, respiration and body temperature

6- Higher mental functions: As memory, learning, thinking, emotions, personality character etc.

An overview of the nervous system

Introduction to the Peripheral Nervous System 1 - Somatic - supplies & receives fibers (neurons) to & from the skin, skeletal

muscles, joints, & tendons 2 - Visceral - supplies & receives fibers to & from smooth muscle, cardiac muscle,

and glands. The visceral motor fibers (those supplying smooth muscle, cardiac muscle, & glands) make up the Autonomic Nervous System. The ANS has two divisions:

Parasympathetic division - important for control of 'normal' body functions, e.g., normal operation of digestive system

Sympathetic division - also called the 'fight or flight' division; important in helping us cope with stress

SENSORY SYSTEM PHYSIOLOGY

The sensory system is the part of the nervous system which is concerned with awareness of the external and internal environment. It consists of sensory receptors, neural pathways that conduct information from the receptors to the brain, and the parts of the brain which is responsible for receiving, processing and storing of these sensory information.Reception / Sensation / Perception

Reception – is to get the information;Sensation – is an awareness of sensory stimuli in brain;Perception – is meaningful interpretation or conscious understanding of sensory data.

Reception → Sensation/Perception

Components of Sensory Physiology1. Sensory receptors: structures that can detect changes in external or internal environment.2. Reception: ability of receptor to absorb energy of a stimulus.3. Transduction: conversion of stimulus energy into membrane potential (Receptor Potential).4. Transmission: receptor potentials transmitted via AP's to CNS.5. Integration: processing of frequency of receptor potentials.

Sensory ReceptorsSensory receptors are specialized structures present at the beginning of the sensory nerves. They are very sensitive to any change in the surrounding environment whether inside or outside the body.

Functions of receptors:

1- Receptors respond to the surrounding stimuli then send information to the CNS which play a role in:

i. Perception of all types of sensations, also give information about the site and intensity of the stimuli.

ii. Regulation of all body functions according to the changes detected by the receptors.

iii. Development of mental activity, learning and memory.2- Receptors are the start points of all body reflexes which regulate the different

functions of the body.

Receptors are essential for the proper functions of the nervous system as well as the other systems, without receptors the nervous system becomes nearly useless.

Characteristics of sensory receptors Adequate stimulus: The type of energy to which a particular receptor responds in

normal functioning is known as its adequate stimulus. Transducer: Transducing stimuli into nerve impulses. Coding: Converting stimulus energy into a signal that conveys the relevant sensory

information to the central nervous system.

Adaptation: Many receptors adapt to the presence of a stimulus and no longer send a signal before the stimulus stops.

Slow adapting: muscle stretch, proprioceptors Fast adapting: olfactory receptors, skin vibration receptors

Some concepts in sensory system Sensory unit: A single afferent neuron with all its receptor endings. Receptive field: The area of the body that, when stimulated, leads to activity in a

particular afferent neuron. Lateral Inhibition: a stimulus that strongly excites receptors in one location will

inhibit the response of nearby afferent neurons.

Classification of sensory receptors:There are different types of receptors, each of which is specialized to respond to a particular stimulus. Receptors can be classified according to the type of stimulus into:

1. Mechano-receptors: These receptors are stimulated by mechanical compression or stretch of the receptor or the surrounding tissues e.g.:

Touch receptors in the skin which are stimulated by light mechanical stimuli. Pressure receptors in the subcutaneous tissues which are stimulated by deep

mechanical stimuli. Stretch receptors in the skeletal muscles, lungs, right atrium, urinary bladder,

stomach, intestine and rectum. Tension receptors in the tendons, which are stimulated by severe stretch or strong

contraction. Joint receptors which send information about the position and movement of the of the

joint Baro-receptors in the carotid sinus and aortic arch. Auditory receptors which are stimulated by sound waves. Vestibular receptors which are stimulated by changes in position and movement.

2. Thermal receptors (Thermoreceptors):These receptors are stimulated by change in the surrounding temperature and divided into

Hot receptors which are stimulated by increase temperature. Cold receptors which are stimulated by decrease temperature.

Thermal receptors are mainly present in the skin to detect the external temperature and in the hypothalamus to detect the internal temperature. These receptors are sometimes present in the deeper tissues and in some viscera.

3. Pain receptors: These receptors are stimulated by any stimulus which produces tissue damage (i.e. noxious stimulus) e.g. severe mechanical, thermal or chemical stimuli. Pain receptors (nociceptors) are present in the skin, deeper tissues and viscera.

4. Chemo-receptors:The receptors are stimulated by chemical stimuli and divided into:

External chemo-receptors e.g. taste and smell receptors. Internal chemo-receptors which are present in:

Carotid and aortic bodies which are stimulated by changes in the chemical composition of blood e.g. CO2, O2 and H+.Hypothalamic chemo-receptors e.g. osmo-receptors, gluco-receptors and receptors for amino acids and fatty acids.

Chemo-receptors present in the brain stem centers (respiratory vaso-motor receptors)

N.B: Cell membrane receptors e.g.: adrenergic receptors, cholinergic receptors, dopaminergic receptors, histamine receptors and hormone receptors. These receptors are not sensory receptors because they are not connected with the sensory nerves.

5. Electromagnetic receptors:These receptors are stimulated by electromagnetic waves of light. These receptors are present in the retina of the eye.

Mechanism of action of receptors: When the adequate stimulus is applied to its specific receptor, it causes opening or

closing of ion channels leading to local depolarization of the membrane of the receptor, a condition known as "receptor (generator) potential".

This receptor potential creates a local electric current between the receptor and the adjacent resting membrane of the nerve. If the receptor potential is strong enough, it leads to generation of an action potential in the first node of Ranvier which then propagates through the sensory nerve.

When the first node of Ranvier becomes repolarized another action potential is produced so long as the stimulus is maintained and the receptor potential is above the threshold level.

Receptor potentialReceptor potential is a graded potential which is caused by the initial ion channel changes and the ion flux. Characteristics of receptor potential include:

A change in permeability of a post-synaptic membrane Often graded = proportional to strength of stimulus May be amplified and/or may be summed May be strong enough (reaches threshold) to generate action potentials. Receptor potential → Action potential

Properties of receptor potential1- It is a graded potential, it is proportional with the intensity of the stimulus. So, it does not obey all or none rule.2- It is of short duration (about 5 m. sec.)

3- It is not followed by refractory period.4- It can be summated either by:

a. Spatial summation, where several sub-minimal stimuli are applied near each other at the same time.

b. Temporal summation, where several sub-minimal stimuli are applied rapidly after each other at the same site.

5- The sub-threshold receptor potential propagates locally with decrement (decrease gradually till it disappears).6- Strong receptor potential generates action potential in the first node of Ranvier, so, it is also called generator potential. The frequency of action potentials generated in the sensory nerve is proportional with the intensity of the receptor potential and also with the intensity of the stimulus.

Mechanism of receptor potential:Receptors can be stimulated by different ways e.g.:Mechano-receptors are stimulated by deformation and stretch of the receptor membrane. This causes opening of the Na+ channels and increase Na+ influx. This leads to depolarization of the receptor (receptor potential).Each chemoreceptor is stimulated by combination with its specific chemical substance. This combination opens the Na+ channels, increase Na+ influx and causes its depolarization.Thermo-receptors are stimulated by changes in the surrounding temperature which leads to changes in the permeability of the receptors causing their depolarization.Pain receptors are stimulated by tissue damage which leads to release of certain chemical substances. The later increases the permeability of the pain receptors to Na+ causing their depolarization.Electromagnetic receptors are stimulated by light waves which change the membrane permeability either directly or indirectly after degradation of the photosensitive pigment present in the photoreceptors (rods and comes).

Properties of Receptors: 1- Excitability: It is the ability of the receptors to respond to different types of stimuli

(internal or external). Receptor acts as transducer by which stimulus is changed into nerve impulse (propagated action potential).

2-Specificity: Each receptor is highly sensitive to a certain stimulus called "the adequate stimulus" and gives only one type of sensation. This law is known as "Muller's law of specific nerve energies

3- Ability to detect the intensity of stimuli: 4- Adaptation: It means gradual decrease in the rate of discharge from the receptors

although the stimulus is still applied. Adaptation is important to prevent sensory overload to the higher centers, and to ignore the less important or unchanged stimuli.

Receptor Specificity:For instance, the retinal receptors are highly sensitive to light (electromagnetic stimulus) and give only the sensation of vision. Some receptors can respond to stimuli other than the

adequate stimulus, but the non-adequate stimuli must be of high intensity. The sensations produced are similar to that produced by the adequate stimuli e.g. a blow to the eye (strong mechanical stimulus) can stimulate the visual receptors and give rise to visual sensation.Almost all receptors can be stimulated electrically to produce sensations similar to that produced by the adequate stimuli.

Specificity is helped by the accessory structures related to the sense organs. These structures increase the sensitivity of the receptor to its adequate stimulus and exclude the non-adequate stimuli e.g. the cornea and the lens of the eye help in focusing the light rays (not other stimuli) on the visual receptors; the external and middle ear structures help the sound waves (not other stimuli) to produce their maximal effect on the auditory receptors.

Specificity is determined by the central connection between the receptors and the higher centers in the cerebral cortex. Each sensory axon is connected with the same type of receptors in a separate pathway till the higher centers.

Ability to detect the intensity of stimuli:Receptors help the higher centers in detecting the intensity of stimuli by:a) Varying the number of stimulated receptors: The strong stimulus stimulates a large number of receptors while the weak stimulus stimulates a few numbers of receptors.b) Varying the rate of discharge from each receptor: The frequency of discharge from each receptor is proportional with the intensity of the stimulus. Strong stimulus increases the magnitude of the receptor potential which increases the frequency of action potentials in the sensory nerve.Weber-Fechner's law states that the frequency of action potential is directly proportional to the logarithm of the intensity of the stimulus applied to the receptors. This enables the receptors to respond to a very wide range of stimulus intensities. So, hundred fold increase in the intensity of the stimulus leads to only two fold increase in the frequency of action potential.

Function of receptors based on Rate of Adaptationa) Rapidly adapting receptors (phasic receptors): These receptors adapt rapidly (within seconds) and completely i.e. stop discharge while the stimulus is still applied e.g. light and deep touch receptors (pacinian corpuscles adapt within a fraction of a second and hair receptors adapt within a second). These receptors are stimulated during the (phasic) changes only (i.e. start, end or change in intensity).One significance of rapid adaptation, for instance, the touch receptors adapt rapidly because their function is to inform the brain about the touch stimuli or about their changes but there is no need to inform the brain continuously about this condition (e.g. touch of clothes) so as not to burden the brain centers.

b) Moderately adapting receptors: These receptors adapt also completely but after a relatively longer time e.g. thermal receptors, taste, smell and visual receptors.Significance of moderately adapting receptors include:

Allowing the thermal receptors to give enough time for the regulatory mechanisms to adjust the body temperature and protect the body from excessive changes in the external temperature. The cold receptors adapt more slowly than the warm receptors.

In the taste and smell receptors, because these receptors play a role in digestion through the conditioned and unconditioned reflexes and also protection of the body against harmful substances (ingested or inhaled).

c) Slowly adapting receptors (tonic receptors): These receptors adapt slowly and incompletely i.e. they continue to discharge (tonic) but at a slower rate. Slowly adapting receptors include pain receptors, proprioceptors, baroreceptors and chemoreceptors.

Significance of slow and incomplete adaptation include: In pain receptors, the continuous sensation of pain prevents the person from using the

injured parts. This prevents more injury and helps the healing process. In proprioceptors, the proprioceptive sensations (sense of position, movement, muscle

stretch etc.) help to maintain the body posture and equilibrium. In baroreceptors and chemo-receptors to maintain ABP, HR, respiratory rate within

normal level.

Coding of sensory informationThe higher centers can discriminate the modality (type) locality (site) and intensity of different sensations by encoding and decoding of their sensory information. This is very important because information are transmitted in the CNS in the form of action potentials which are similar in all conditions.1- Discrimination of modality (type) of sensations: The higher centers can discriminate the modality of sensations by the following:Specificity of the receptors: (Muller's law) Each receptor is highly sensitive to its adequate stimulus and gives only one type (modality) of sensation.Specificity of the sensory pathway: Each sensory neuron is connected peripherally with the same type of receptors and connected centrally with a specific pathway. If this pathway is stimulated (no matter how or where) it will produce the same type of sensation received by the receptors. Termination in a specific area in the cerebral cortex: The nerve fibers from the retina of the eye terminate in the visual areas of the cerebral cortex, and nerve fibers from the ear terminate in the auditory areas and so other fibers.

2- Discrimination of locality (site) of sensation: Each receptor (or group of the same receptor) is connected through a separate pathway to a certain point in the cerebral cortex. Stimulation of this point in the cerebral cortex (or any where in the pathway) projects the sensation to the location of the receptor. This is known as " The law of projection". So, each skin area supplied by a single neuron (receptive field of that neuron) is represented in a certain point in the cerebral cortex. The size of the receptive field varies greatly according to the site (being small in the finger tips and great in the trunk). The higher centers can discriminate the locality of sensation

perfectly if the size of the receptive field is small, but the discrimination of locality is poor if the receptive fields is large.

3- Discrimination of intensity of sensation: The higher centers can discriminate the intensity of sensation by: a) Varying the number of stimulated receptors: Strong stimulus stimulates a large number of receptors and produces a strong sensation, while the weak stimulus stimulates a few receptors and produces a weak sensation. b) Varying the rate of discharge from each receptor: Strong stimulus increases the rate of discharge from each receptor and produces a strong sensation, while the weak stimulus decreases the rate of discharge and produces a weak sensation.

MOTOR SYSTEM PHYSIOLOGY

IntroductionThe motor system is the part of the central nervous system that is involved with movement. It consists of the pyramidal and extrapyramidal system. The term motor system refers to the neural pathways that control the sequence and pattern of muscle contractions. The structures responsible for the neural control of posture and movement are distributed throughout the brain and spinal cord.

The motor neurons are found in the brainstem and spinal cord and their excitability is influenced by neural pathways that may form local circuits or may arise in a variety of brain areas. Thus there is a kind of hierarchical arrangement of so-called motor centres from the spinal cord up to the cerebral cortex.

A vast array of reflexes are controlled by neural circuits within the spinal cord, and these reflex circuits form a system that organizes the basic motor patterns of posture and movement. Superimposed on these local circuits are influences from higher centres in the brain. Postural control is exerted largely at the level of the brainstem, while goal-directed movements require the participation of the cerebral cortex. The basal ganglia and cerebellum both play an important role in motor control though neither is directly connected with the spinal motoneurons. Instead, they influence the motor cortex by way of the thalamic nuclei.

Fig. A diagrammatic representation of the motor systems of the body showing possible interactions between them

Types of motor activities include Voluntary movements, Reflex movements, and Rhythmic motor activity. Motor System include: Tracts, e.g. Corticospinal (skillful Voluntary movement), Corticobulbar and Bulbospinal (Extrapyramidal); The Basal Ganglia (regulator) and The Cerebellum (regulator)Components of the Motor System include the:(I) Upper motor neuron (corticospinal & corticobulbar tracts which starts from motor cortex and ends in (a) Cranial nerve nucleus (corticobulbar). (b) Anterior horn of spinal cord in opposite side (corticospinal tracts).(II) Lower Motor Neuron which starts from anterior horn of spinal cord and ends in appropriate muscle of the same side e.g. all peripheral motor nerves.

a

Fig. a. The Motor System: schematic diagram showing the interactions between the tracts and structures involved in motor activities. b. Relays of the corticospinal tracts (pyramidal tracts) from the cortex and their terminations (synapses)

Higher centres controlling voluntary movements

Cortical Motor Areas include Primary Motor Cortex (M-I), Supplementary Motor Area (M-II), Premotor Cortex (PMC), Frontal Eye Field Area, Broca’s Area for speech

Motor cortex Primary motor cortex ( M1) Premotor area (PMA) Supplementary motor area (SMA)

Note: All the three projects directly to the spinal cord via corticospinal tract. Premotor and supplementary motor cortex also project to primary motor cortex and is involved in coordinating & planning complex sequences of movement (motor learning).

b

Voluntary movements are controlled by the following cortical motor areas:I) Primary motor area (area 4):

It occupies the pre-central gyrus of the frontal lobe. In area 4 the body is represented upside down (inverted) i.e. foot in the upper part and face in the lower part. It supplies mainly the muscles in the opposite side of the body (contra-lateral) through pyramidal tract. The area of representation of any part of the body is related to its motor activity. So, the areas of the fingers, lips and tongue are wider than areas of the trunk and thigh. Functions of area 4:

1- It initiates voluntary, fine, discrete (isolated) movement in the opposite side of the body. So, electrical stimulation of the finger area leads to contraction of a single muscle or a small group of muscles.

2- It facilitates stretch reflex and muscle tone of the opposite side of the body (one of the supra-spinal facilitatory centres).

3- It also facilitates spinal reflexes and spinal centres.

Effects of lesion in area 4:1- Paralysis of the muscles of the opposite side of the body. 2- Decrease muscles tone is the paralyzed muscle (flaccid paralysis).3- Loss of reflexes: Superficial reflexes (e.g. abdominal & cremastric reflexes) and deep

reflexes (e.g. tendon jerks). 4- Babinski's sign; abnormal response of planter reflex, scratching the lateral border of

the sole produces dorsi-flexion of the big toe instead of planter flexion.

II) Pre-motor area (area 6):It lies in front of area 4. In area 6 the body is also represented upside down (inverted). It

affects the muscles of the opposite side of the body through extra-pyramidal tracts. It affects the muscles indirectly through its connection with basal ganglia, reticular formation, red nucleus and vestibular nucleus. Functions of area 6:1- As regards voluntary movements, area 6 produces:

a) Regulation of the complex voluntary movements initiated by area 4 because it contains the memory of the highly skilled movements.

b) Initiation of gross movements produced by proximal muscles.c) Fixation movements which occur in the trunk and proximal parts of the limbs

(shoulder and elbow) to help fine voluntary movements produced by the distal parts (fingers).

d) Associated movements: Some voluntary movements are usually associated with certain involuntary movements e.g.:- Swinging movements of arms during walking.- Facial expression which reflects the emotional state of the person.

2- It inhibits stretch reflex and MT of the opposite side of the body (through its connection with basal ganglia and reticular formation).

3- It inhibits spinal reflexes and spinal centres.4- It inhibits grasp reflex.

Grasp reflex: touching the palmer surface of the hand produces firm closure of the hand over the touched object. The centre of the grasp reflex in the midbrain is normally inhibited by area 6 of the frontal lobe. Grasp reflex is not normally present, but it appears in the followed conditions:

- In monkeys because frontal lobe does not develop in these animals.- In adults with lesion in area 6, because grasp centre is released from inhibition.

5- It has some autonomic functions, its stimulation produces changes in the heart rate and ABP.

6- Pre-motor area contains the following special areas:a- Broca's area of speech (area 44 & 45): It lies anterior to the primary motor area 4

immediately above the lateral sulcus. It is present in the dominant cerebral hemisphere (in the left side in the right-handed persons). It is the motor centre for spoken words. Its lesion leads to motor aphasia.

b- Frontal eye movement area: It lies immediately above Broca's area. It controls voluntary movements of the eyes (and eye lids) towards the different objects.

c- Head rotation area: It lies above the eye movement area and it is closely associated with it. It directs the head towards the seen objects.

d- Hand skills area (Exner's area): It lies anterior to the hand and finger region of the area 4. It controls the skilled movement of the hands. Its lesion leads to motor Apraxia (inability to do skilled movements) and Agraphia (inability to write).

III) Supplemental motor area:It lies immediately anterior and superior to pre-motor area (mainly on the edge and

medial side of the cerebral hemisphere). The body representation lies horizontal with the head anterior and the leg posterior. It is connected with the primary motor area and pre-motor area as well as basal ganglia and cerebellum. It has the following functions:

1- It helps in control of the complex movements which involves large group of muscles and also involves both sides of the body.

2- It adjusts the suitable position and helps fixation of the proximal parts to facilitate the fine movement of the distal parts.

Descending Motor Tracts

(I) Pyramidal Tract :Origin: It arises from the following cortical areas:

a)Motor areas: Primary motor area 4 (mainly), pre-motor area 6 (including Broca's area of speech, frontal eye movement area, head rotation area, and hand skills area), and supplemental area.b)Somatic sensory area: Primary sensory area (area 3, 1, 2) and secondary sensory area (area 5,7).

Course: From C.C to corona radiate then the fibres collect together and pass in the internal capsule (occupy the genu and anterior 2/3 of the posterior limb). Then it passes in the brain stem:

A) Some fibres cross to the opposite side to end at the nuclei of the cranial nerves:- The pyramidal tract fibres which end at the nuclei of the cranial nerves 3, 4, 6 (which supply the eye muscles) are called cortico-nuclear tract.- The pyramidal tract fibres which end at the nuclei of the remaining motor cranial nerves are called cortico-bulber tract.

B) The remaining fibres are called cortico-spinal tract pass as follow:- In the midbrain; occupy the middle 3/5 of cerebral peduncle.- In the pons; the fibres are separated into separate bundles by transverse pontine fibres.- In the medulla oblongata; in the upper medulla the fibres collect again to form the

pyramid, in the lower medulla the fibres divide into 3 parts:1- Most of the fibres (80 – 90%) cross to the opposite side in the lateral column (crosses

cortico-spinal tract) and end at the AHC of the opposite side (directly or through inter-neurons).

2- Most of the remaining fibres (10-20%) pass in the same side in the anterior column forming (Direct cortico-spinal tract) which ends as follow:

- The greater part cross again to end at the AHC of the opposite side. - The other part end at the AHC of the same side.3- The other fibres pass with the crosses cortico-spinal tract coming from the opposite

side to end at the AHC of the same side.NB: Some pyramidal tract fibres (about 2%) do not cross to the opposite side and

terminate at the AHC and cranial nuclei of the same side. These uncrosses fibres innervate the muscles which act together as muscles of mastication, deglutition, speech, respiratory and abdominal muscles. These fibres also allow partial recovery of voluntary movements in hemiplegia.

Functions of pyramidal tract: The same as functions of area 4.Effects of pure pyramidal tract lesion: The same as lesion of area 4.Pyramidal tract lesion at different levels:

1- Lesion of area 4: Mono-plegia in the opposite side because lesion affects only part of area 4 which is a wide area.

2- Lesion in corona radiate: If the lesion is small → mono-plegia in the opposite side. If the lesion is large → hemi-plegia in the opposite side.

3- Lesion in internal capsule → hemi-plegia in the opposite side.4- Lesion in brain stem: crossed hemi-plegia which means hemi-plegia (UNML) in

opposite side and cranial nerve lesion (LMNL) in the same side:oIn midbrain C III & IV.oIn pons C V , VI & VII.oIn medulla C IX, X, XI & XII.

5- Lesion in the spinal cord:a)Above the brachial plexus. Unilateral lesion → spinal hemi-plegia in the same side. Bilateral lesion → Quadriplegia (paralysis of 4 limbs).b)Below the brachial plexus and above lumbo-sacral plexus: Unilateral lesion → Mono-plegia in the same side. Bilateral lesion → Paraplegia (paralysis of both lower limbs).

(II) Extra-pyramidal tracts:These are all descending tracts other than pyramidal tract.

Origin: Extra-pyramidal tracts start nearly from most areas of the CC mainly from area 6, area 4S and also area 4.

They don't reach AHC directly but through their connection with other sub-cortical areas e.g. basal ganglia, reticular formation, vestibular nuclei, red nuclei and olivary nuclei.

Extra-pyramidal tracts:

1-Rubro-spinal tract:Origin: From the red nucleus in the midbrain. This tract crosses to the opposite side and descends in the lateral column of the spinal cord.Functions:

- Inhibitory to MT.- It acts as an additional pathway for transmission of the cortical motor orders to the lower

motor neurons.

2- Tecto-spinal tracts:

Lateral Tecto-spinal tract:Origin: Superior colliculus in the tectum of the midbrain (which receives visual impulses) this tract crosses to the opposite side and descends in the cervical segments of the spinal cord. Some fibres synapse with the L H Cs of thoracic 1, 2 (origin of sympathetic to head & neck).Functions: It is responsible for visual attack and defensive reactions.Defensive reactions:-Closure of the eyes, raising the hands in front of the face and turning the head away to avoid the source of injury.-Rat escape away when it sees the cat.Attack reactions:-Turning the head towards a beautiful sight.-Cat attacks when it sees the rat.

Ventral tecto-spinal tract:Origin: Inferior colliculus in the tectum of the midbrain (which receives auditory impulses). This tract crosses to the opposite side and descends in the cervical segments of the spinal cord.Functions: It is responsible for auditory attack and defensive reactions.Defensive reactions:-Running away when a person hears the sound of a car behind him.-Rat escapes away when it hears the cat.Attack reactions:-Turning the head towards the source of a familiar sound.-Cat attack when it hears the rat.

3- Reticulo-spinal tracts: a) Lateral reticulo – spinal tract:

Origin: Reticular formation in the medulla. This tract crosses to the opposite side.Function: Inhibition of MT.

b) Ventral reticulo-spinal tract:Origin: Reticular formation in the pons. The tract passes in the same side.Function: Facilitation of MT.

4- Vestibulo-spinal tracts:Origin: Vestibular nuclei in the medulla. Both lateral and ventral vestibule- spinal

tracts pass in the same side of the spinal cord.Functions: Facilitation of MT, control of equilibrium, and maintain posture.

5- Olivo-spinal tract:Origin: Inferior Olivary nucleus in the medulla oblongata.This tract descends in the

same side of the spinal cord.Function: Facilitation of MT.

Functions of extra-pyramidal tracts:1) Regulation of equilibrium and maintain posture: These tracts control MT so as to maintain normal posture and to control equilibrium e.g.:-On standing position, the MT ↑ in the antigravity muscles to maintain normal posture.

-Change in the position leads to change in the distribution of the MT so as to maintain equilibrium e.g. if a person is pushed backwards the MT ↑in the abdominal ms. And ↓ in the back ms. If he is pushed forward the reverse occurs.2) Fixation movements: These are involuntary movements which occur in the trunk and proximal parts of the limbs to help the fine voluntary movements of the distal parts e.g. during writing the trunk, shoulders and elbow are involuntary fixed so as the voluntary movements of the fingers can be done easily and accurately.3) Associated movements: The voluntary movements are usually associated with certain involuntary movements e.g.: Swinging movements of the arms during walking. Emotional expression e.g. facial expression which reflects the emotional state of the person.4) Coordination of movements: Coordination occurs by cerebellum through its connection with the extra-pyramidal tracts. By coordination the complex movements can be performed easily.

Reflex action and reflex arcs

Reflexes represent the simplest form of irritability associated with the nervous system. Reflex arcs include at least two neurons, an afferent or sensory neuron and an efferent or motor neuron. The fibre of the afferent neuron carries information about the environment from a receptor towards the CNS while the efferent fibre transmits nerve impulses from the CNS to an effector.

Reflexes may be (and often are) subject to modulation by activity in the CNS.In the simplest reflex arc, there are two neurons and just one synapse. Therefore such reflexes are known as monosynaptic reflexes. Other reflex arcs have one or more neurons interposed between the afferent and efferent neurons. These neurons are called interneurons or internuncial neurons. If there is one interneuron, the reflex arc will have two synaptic relays and the reflex is called a disynaptic reflex. If there are two interneurons, there will be three synaptic relays so that the associated reflex would be trisynaptic. If many interneurons are involved, the reflex would be called a polysynaptic reflex.

Examples are the stretch reflex (monosynaptic), the withdrawal reflex (disynaptic), and the scratch reflex (polysynaptic).

The knee jerk is an example of a dynamic stretch reflexA classic example of a stretch reflex (also known as the myotactic reflex) is the knee-jerk or tendon-tap reflex which is used routinely in clinical neurophysiology as a tool for the diagnosis of certain neurological conditions.

The flexion reflexIn this protective reflex, a limb is rapidly withdrawn from a threatening or damaging stimulus. It is more complex than the stretch reflex and usually involves large numbers of inter-neurons and proprio-spinal connections arising from many segments of the spinal cord. Withdrawal may be elicited by noxious stimuli applied to a large area of skin or deeper tissues (muscles, joints, and viscera) rather than from a single muscle as in the stretch reflex. The receptors responsible are called nociceptors and they give rise to the afferent impulses that are responsible for the flexion reflex.

The crossed extensor reflexStimulation of the flexion reflex, as described above, frequently elicits extension of the contralateral limb about 250 ms later. This crossed extension reflex helps the subject to maintain posture and balance. The long latency between flexion and crossed extension represents the time taken to recruit interneurons.

The Golgi tendon reflexThis reflex, which is the result of activation of Golgi tendon organs, complements the tonic stretch reflex and contributes to the maintenance of posture.

Fig.

(a) The stretch reflex arc. Note that this reflex arc comprises only two neurons and one synapse. Therefore it is a monosynaptic reflex.

(b)The basic flexor (withdrawal) reflex arc. In this case, there are three neurons and two synapses in the basic arc. Therefore the reflex in its simplest form is disynaptic.

AUTONOMIC NERVOUS SYSTEM

Introduction

The peripheral nervous system, can be classified according to its function into Somatic nervous system, supplies the body wall and extremities AND Autonomic (visceral) nervous system (ANS), supplies the internal organs (the viscera)

The ANS supplies the internal organs (the viscera) by a) Autonomic sensory fibres; carry sensory information from the internal organs

(heart, lungs, stomach, intestine, kidney, urinary bladder, rectum etc.) to the central nervous system. Autonomic sensory (afferent) fibres carry the visceral sensations (pain, sense of desire of micturition and defecation etc.), and the afferent impulses of autonomic reflexes (e.g. micturition reflex).

b) Autonomic motor fibres, carry motor orders from the central nervous system to the smooth (involuntary) muscles, cardiac muscle, and glands.

The autonomic (visceral or involuntary) nervous system is that part of the nervous system which controls the activity of the viscera, there are two divisions of the autonomic nervous system; the sympathetic (thoraco - lumbar) and the parasympathetic (cranio - sacral) divisions.

The parasympathetic postganglionic fibres liberate acetylcholine, so they are called cholinergic fibres. Most sympathetic postganglionic fibres liberate noradrenaline, so they are called adrenergic. However, sympathetic postganglionic fibres to the sweat glands and blood vessels of skeletal muscles liberate acetylcholine i.e. cholinergic.

Sympathetic Nervous System

The Sympathetic Nervous System prepares the body for vigorous activity (fight or flight) in response to emergency situations (fear, intense muscular exercise, stress, haemorrhage, cold, etc.)

Origin: The sympathetic nervous system originates from the lateral horn of the spinal gray matter from the first thoracic to the second (sometimes the third) lumbar segments, hence the name thoraco-lumber outflow.

Course and distribution: The sympathetic preganlionic fibres leave the spinal cord with the ventral roots of the spinal nerves. The preganglionic fibres are thin myelinated fibres (type B) and appear whitish in colour. They are called white rami communicants. The preganglionic fibres synapse (relay) in the sympathetic ganglia with a large number of postganglionic neurons. The sympathetic ganglion acts as a distributing centre. The ratio of preganglionic to postganglionic fibres is 1:20 or more, so the sympathetic actions are widespread. The postganglionic fibres (non- myelinated) proceed to supply the visceral structures.

The sympathetic gangliaThe sympathetic ganglia are:1- Lateral (paravertebral) ganglia: These ganglia lie on both sides of the vertebral column forming the sympathetic chains. They extend from the base of the skull to the front of the coccyx where they meet at the coccygeal ganglion. The number of ganglia in the sympathetic

chain is about 22-24 on each side and are named according to the region. In cervical region, there are three ganglia (superior, middle, and inferior cervical ganglia).

They are relatively large and represent the fusion of two or more smaller ganglia. The superior cervical ganglion is the largest of the three ganglia. The middle cervical ganglion lies near the inferior ganglion and it may be absent. The inferior cervical ganglion is usually fused with the first thoracic ganglion and occasionally with the second as well, to form the stellate ganglion.

2- Collateral ( prevertebral ) ganglia: These ganglia lie between the sympathetic chain and the viscera. They are closely related to the aorta and its branches and named according to these branches e.g. celiac, superior mesenteric, inferior mesenteric and aortico-renal ganglia. From these ganglia, postganglionic fibres arise and pass with the blood vessels to supply the viscera.

3- Terminal sympathetic ganglia: A few, relatively small sympathetic ganglia lie closer to the visceral organs and especially close to the rectum, urinary bladder and reproductive organs in the pelvis. These ganglia send out short postganglionic fibres to the viscera.

Functions of the sympathetic nervous system1) Sympathetic to head and neck:Origin: From the lateral horn cells (LHC) of the first and second thoracic segments.Relay: In the superior cervical ganglion.Functions:i) In the eye:

Motor to the dilator pupillae muscle leading to dilatation of the pupil. Motor to the smooth muscles of the eye lids leading to elevation of the upper and

lowering of the lower eye lids i.e. widening of the palpebral fissure. Motor to the smooth muscles of the eye ball (Muller’s muscle) present behind the eye

leading to forward protrusion of the eye i.e. exophthalmos. Vasoconstriction of the blood vessels of the lacrimal glands. Relaxation of the ciliary muscle helping the eye to see far objects.

ii) In the salivary glands: Acini: Salivary secretion which is little in volume, viscid, and rich in organic

substances. Smooth muscles around both the acini and the ducts: Contraction which leads to

squeezing of the duct content outside. Blood vessels: Vasoconstriction.

iii) In the skin: Sweat secretion. Contraction of pilo-erector muscles causing erection of hairs. Vasoconstriction and vasodilatation to the skin blood vessels, but the vasoconstrictive

action is more powerful.iv) In the brain:

No effect or slight vasoconstriction of the cerebral blood vessels.

2) Sympathetic to thorax:Origin: From the L.H.C. of upper four or five thoracic segments.Relay: In the superior, middle, inferior cervical ganglia and the upper four thoracic ganglia.Functions:

i) In the heart: Stimulation of all properties of the cardiac muscle leading to an increase in the heart

rate, force of cardiac contraction, conduction velocity and excitability. Dilatation of the coronary blood vessels leading to an increase in the blood supply to

the cardiac muscle.ii) In the lungs:

Relaxation of the muscles of the bronchi and bronchioles leading to widening of the air passages.

Decreased mucous secretion in the air passages. Slight vasoconstriction of the pulmonary blood vessels.

3) Sympathetic to abdomen:Origin: From the L.H.C. of thoracic segments 6 - 12.Relay: Preganglionic fibres form the splanchnic nerves which relay in collateral ganglia (celiac, superior mesenteric and aortico - renal) and terminal ganglia.Functions:i) In the gastrointestinal tract:

Relaxation of the smooth muscles of the stomach, small intestine and proximal part of the large intestine but motor to the sphincters.

ii) In the liver: Glycogenolysis i.e. conversion of the liver glycogen into blood glucose. This effect is

produced by adrenaline secreted from the supra renal gland. Relaxation of the wall of the gall bladder and motor to its sphincter.

iii) In the spleen: Contraction of the smooth muscles present in the splenic capsule and trabeculae

leading to the addition of blood rich in red and white blood cells into the general circulation.

iv) In the blood vessels: Vasoconstriction to the blood vessels of the stomach, intestine, liver, pancreas and

kidneys.v) In the supra renal medulla:

Secretion of two hormones (adrenaline 80% and noradrenaline 20%) into the general circulation. These hormones have almost the same effects throughout the body as direct sympathetic stimulation except:

Their effects are more prolonged than direct sympathetic stimulation (about 10 times) because these hormones are slowly removed from the blood.

Adrenaline has a powerful metabolic effect. It increases the metabolic rate, blood glucose level (due to stimulation of glycogenolysis), free fatty acids and triglycrides (due to stimulation of lipolysis).

4) Sympathetic to pelvis:Origin: From the L.H.C. of the first, second and sometimes the third lumbar segments.Relay: In the collateral and terminal ganglia.Functions:i) In the urinary bladder:

Relaxation of the smooth muscles of the wall of the urinary bladder and contraction of the internal uretheral sphincter thus leading to retention of urine (help filling of the bladder).

ii) In the rectum:

Relaxation of the smooth muscles of the wall of the rectum and contraction of the internal anal sphincter leading to retention of the faeces (help storage of faeces).

iii) In the sex organs: Contraction of the smooth muscles of the vas deferens, seminal vesicle, ejaculatory

duct and prostate leading to ejaculation of semen. Vasoconstriction of the blood vessels of the pelvic viscera including that of the

external genital organs leading to shrinkage of the penis and clitoris.

5) Sympathetic to upper limbs, lower limbs, thoracic and abdominal walls:Origin:

Upper limbs: From the L.H.C. of thoracic 5 to 9. Lower limbs: From the L.H.C. of thoracic 10 to lumbar 2. Thoracic and abdominal walls: From the LHC of all thoracic and upper 2 lumbar.

Relay: In the sympathetic chain. The postganlionic fibres join the spinal nerves as gray rami to supply the involuntary structures in the skin and skeletal muscles.Functions:In the skin:

Sweat secretion. Contraction of pilo-erector muscles causing erection of hairs. Vasoconstriction and vasodilatation to the skin blood vessels, but the vasoconstrictive

action is more powerful.In the skeletal muscles:

Vasodilatation of the skeletal muscle blood vessels. Orbelli phenomenon: Sympathetic stimulation of the skeletal muscles causes better

contraction, delayed fatigue, and early recovery of the muscle after fatigue. It is due to:

i) An increase in the blood flow to the muscles as a result of vasodilatation. This provides the muscles with more oxygen and glucose and removes waste products from them.ii) An increase in the sensitivity of the motor end plate to the action of acetylcholine.iii) Activation of phosphorylase enzyme which is needed for glycogen breakdown and release of energy in the muscle.

Parasympathetic Nervous System

The Parasympathetic Nervous System control the activity of the viscera during rest and sleep. It deals with anabolic activities leading to restoration and conservation of body energy. In other words; in times of danger, the sympathetic system prepares the body for violent activity, when the danger is over, the parasympathetic system reverses these changes.

A) The cranial part arises from the visceral motor nuclei of the following cranial nerves: III, Oculomotor nerve: arises from Edinger Westphal nucleus in the mid brain. VII, Facial nerve: arises from the superior salivary (salivatory) nucleus in the pons. IX, Glossopharyngeal nerve: arises from the inferior salivary (salivatory) nucleus in

the medulla oblongata. X, Vagus nerve: arises from the dorsal motor nucleus of the vagus in the medulla

oblongata.

B) The sacral part: arises from the second, third and fourth sacral segments. The preganglionic fibres unite to form the pelvic nerve.Course and distribution:

The preganglionic parasympathetic fibres are thin myelinated fibres (type B) like that of the sympathetic but they are relatively longer. They synapse in the parasympathetic ganglia with few postganglionic neurons. The axons of the postganglionic neurons are very short and unmyelinated (type C). The ratio of the preganglionic to the postganglionic neurons in the parasympathetic ganglia is only 1:2. Therefore, the activity of the parasympathetic system is more localized.

The postganglionic fibres of the Oculomotor, Facial and Glossopharyngeal nerves supply the involuntary structures in the head, those of the Vagus nerve supply the thoracic and abdominal viscera, while those the pelvic nerve supply the pelvic viscera.

The parasympathetic gangliaThe parasympathetic ganglia are:

The ciliary ganglion for relay of the Oculomotor nerve. The spheno-palatine and the submandibular ganglia for relay of the Facial nerve. The Otic ganglia for relay of the Glossopharyngeal nerve. The terminal (intrinsic) ganglia for relay of the Vagus and pelvic nerves. These

ganglia lie on the surface or within the effector organs.

Functions of the parasympathetic nervous system:A) Cranial parasympathetic outflow:

III: Oculomotor nerve:Origin: From the Edinger Westphal nucleus in the mid brain.Relay and Functions: In the ciliary ganglion, from which postganglionic fibres run in the short ciliary nerves to causes:

Contraction of the constrictor pupillae muscle leading to narrowing of the pupil i.e. miosis.

Contraction of the ciliary muscle leading to an increase in convexity of the lens which helps accommodation of the eye to near vision.

VII: Facial nerve:Origin: From the superior salivary nucleus in the pons.Relay and functions: In the spheno-palatine ganglion, from which postganglionic fibres pass to the lacrimal glands causing secretion of tears and vasodilatation, and also to the mucous membranes of nose, soft palate and pharynx causing secretion of mucous and vasodilatation.The chorda tympani branch of the Facial nerve relay in the submandibular ganglion from which the postganglionic fibres pass to the submandibular and sublingual salivary glands causing salivary secretion (large in volume, watery and poor in organic substances i.e. true secretion) and vasodilatation. The chorda tympani nerve causes also vasodilatation in the mucous membranes of the anterior two thirds of the tongue and floor of the mouth.

IX: Glossopharyngeal nerve:Origin: From the inferior salivary nucleus in the medulla oblongata.Relay and functions: In the Otic ganglion from which postganglionic fibres pass to the parotid salivary gland causing secretion (true secretion) and vasodilatation. These fibres also cause vasodilatation in the posterior third of the tongue.

X: Vagus nerve:Origin: From the dorsal motor nucleus of the vagus present in the medulla oblongata.Relay: In the terminal ganglia present in the thoracic and abdominal viscera.Functions: About 75% of all parasympathetic nerve fibres are in the vagus nerves, passing to the entire thoracic and abdominal viscera.

Functions of the Vagus Nerve1) In the thorax:i) In the heart: Inhibition of all properties of the cardiac muscle leading to decrease in the heart

rate, force of atrial contraction, conduction velocity and excitability. Vasoconstriction of the coronary blood vessels.ii) In the lungs: Motor to the smooth muscles of the bronchi and bronchioles. Secretory to the mucous glands in the air passages. Vasodilatation to the pulmonary blood vessels.

2) In the abdomen:i) In the gastrointestinal tract: Motor to the smooth muscles of the esophagus, stomach, small intestine and

proximal part of the large intestine but inhibitory to their sphincters. In other words, it helps deglutition, gastric motility and evacuation, and stimulates peristaltic movements in the intestine.

Secretory to the gastric glands, producing gastric juice rich in HCl, and secretory to the duodenal (Brunner’s) glands, producing mucous secretion.

ii) In the liver: Stimulates secretion of hepatic bile. Motor to the wall of the gall bladder and inhibitory to its sphincter (sphincter of

Oddi).iii) In the pancreas: Secretion of the pancreatic juice which is rich in enzymes. Stimulation of insulin secretion from the beta cells of the islets of Langerhans.

B) Sacral parasympathetic outflow:Origin: From the sacral segments 2,3 and 4. The preganglionic fibres unite to form the pelvic nerve.Relay: In the terminal ganglia present in the wall of the pelvic viscera.Functions:i) In the urinary bladder:

Motor to the wall of the urinary bladder and inhibitory to internal uretheral sphincter leading to micturition.

ii) In the distal part of the large intestine and rectum: Motor to the wall and inhibitory to the internal anal sphincter leading to

defecation.iii) In the sex organs:

Vasodilatation of the blood vessels of the pelvic viscera including that of the sex organs leading to erection of penis and clitoris and congestion of the labia. So, the pelvic nerve is sometimes called the “nervous erigens”.

Secretory to the seminal vesicles and prostate.

Control of Autonomic Functions

Most of the autonomic functions are mediated through the autonomic reflexes as in the gastrointestinal, cardiovascular, genitourinary and respiratory functions. The autonomic reflexes begin by afferent fibres from the viscera which synapse at the lateral horn cells in the spinal cord or at the visceral part of the cranial nuclei in the brain stem. The efferent fibres emerge from the central nervous system as preganglionic fibres which relay in the autonomic ganglia before they reach the effector organs.

The autonomic reflexes are controlled by centres present at the following sites:1-Spinal cord: For primitive autonomic reflexes.

2-Brain stem a- The medulla oblongata contains centres that control heart rate, arterial blood

pressure, respiration, gastrointestinal motility and secretion, adrenaline secretion and vomiting.

b- The pons contains centres that control respiration and salivary secretion. c-The mid brain contains centres that controls micturition and pupillary response

to light and near vision. etc.

3-Hypothalamus: The hypothalamus plays an important role in maintaining the internal environment constant by affecting the autonomic nervous system and the hormonal secretion. The hypothalamus can affect the activity of almost all the brain stem autonomic centres. In general stimulation of the anterior nuclei of the hypothalamus increases the parasympathetic functions (decrease heart rate, decrease blood pressure. pupillary constriction, increase motility of the gastrointestinal tract and bladder contraction). Stimulation of the posterior nuclei increases the sympathetic functions (increase heart rate, increase blood pressure, pupillary dilatation and erection of hairs). 4-Cerebral cortex: Certain areas in the cerebral cortex (visceral or limbic cortex) can modify the autonomic functions through its connection with the hypothalamus and reticular formation This occurs as in the following conditions:

Certain cardiovascular and gastrointestinal functions are influenced by psychological factors. If these factors are strong enough they may cause autonomic induced diseases as peptic ulcer, constipation, and heart palpitation.

Voluntary control of micturition and defecation. Increase blood flow in the skeletal muscles in anticipation of voluntary muscular

and sexual activities. Some conscious control can be produced by yoga players on a number of

autonomic functions including heart rate, respiratory rate, gastrointestinal motility

Differences between somatic and autonomic nervous Systems

Somatic nervous system Autonomic nervous systemConnection: With the body wall and extremities i.e.

skin and skeletal system (muscles, joints and bones)

With the smooth muscles, cardiac muscle and glands

Sensory (afferent)Fibers:

Carry cutaneous sensation and deep sensationsCarry afferent impulses of somatic reflexes which control activity of skeletal muscles (e.g. withdrawal ref.)

1. Carry visceral sensation.2. Carry afferent impulses of autonomic reflexes which control the activity of the viscera (e.g. autonomic reflex)

Motor (efferent)Fibers:

1.Innervate skeletal (voluntary) muscles

1. Innervate smooth (involuntary) muscles, cardiac muscles, and glands.

2. Voluntary. 2. Involuntary.3. Arise from the anterior horn cells (AHC) in the spinal cord and the somatic motor nuclei in the brain stem.

3. Arise from the lateral horn cells (LHC) in the spinal cord and the visceral motor nuclei in the brain stem.

4. Only one neuron arises from the AHC to the skeletal muscles i.e. motor fibers do not synapse outside CNS.

4. Two neurons (a) preganglionic neuron arises from LHC and synapses in autonomic ganglia and (b) postganglionic neuron passes from the ganglia to the viscera

5. Thick myelinated fibers (type A) 5. Preganglionic fibers are thin myelinated (type B) and post- ganglionic fibers are unmyelinated (type C)

6. Stimulation of somatic motor fibers always leads to excitation (contraction) of skeletal muscles.

6. Stimulation of autonomic motor fibers may lead to either excitation or inhibition of effector organs

7. Cutting of somatic motor nerves leads to paralysis

7. Cutting of autonomic motor nerves does not lead to paralysis

8.Chemical transmitter is acetylcholine 8.Chemical transmitter at preganglionic nerve endings is acetylcholine and at postganglionic nerve endings are acetylcholine and noradrelaline.

HIGHER MENTAL FUNCTIONS

I. Learning:Learning is a modification of behaviour which results from training, observation and experience.

II. Memory: It is the process of storage of information. It has the following types:

1- Short term memory: It is the ability to retain few facts (words or numbers) for few minutes to few hours. It depends upon the continued activity of the nervous system because inactivation of the brain (e.g. by anaesthesia, hypoxia or ischemia) results in loss of short term memory. Short term memory may be due to reverberating circuits.2- Long term memory: It is the storage of information which can be recalled after several hours or years. It results from structural changes in the form of protein synthesis or formation of new synaptic contacts.

III. Speech:It is the highest mental function in man through which he can express his thoughts either by written or spoken words.Speech centres:These centres are necessary for proper speech, they are present in the dominant hemisphere; commonly (90%) in the left side in the right handed persons, and in the right side in the left handed persons.A) Sensory speech centres:1- Visual speech centre (visual association area or area 18, 19); in the occipital lobe to understand the meaning of the object seen and written words.2- Auditory speech centre (auditory association area or area 22); in the temporal lobe to understand the meaning of the spoken words.B) General interpretative area (ideational centre or area 39, 40); in the posterior tip of the lateral sulcus occupying the angular gyrus and supra-marginal gyrus. Ideational centre is a connection between sensory and motor speech centres; in which ideas and thoughts originate. It receives impulses from the visual association area (18, 19), auditory association area (22) and sensory association area (5, 7), then send impulses to the motor speech centres either Broca's area of speech or Exner's area.C) Motor speech centres:1- Broca's area (speech centre or area 44, 45) in the frontal lobe. It receives impulses from ideational centre and send impulses to motor area of the face (area 4c) which send impulses (through cortico-bulbar tract) to cranial nuclei to the muscles of speech in the tongue, lips and larynx.2- Exner's centre (writing centre or area 46) in the frontal lobe. It receives impulses from ideational centre and send impulses to motor area of the arm (area 4b) which send impulses (through pyramidal tract) to AHC to hand muscles.

Aphasia: It means inability to express thoughts either by spoken or written words.It may be:I. Sensory aphasia:a) Visual aphasia: It is due to lesion of the visual speech centre (area 18, 19). The patient can see, but he can't understand the written words.b) Auditory aphasia: It is due to lesion of the auditory speech centre (area 22). The patient can hear, but he can't understand the spoken words.c) General sensory aphasia (ideational aphasia): It is due to lesion in the ideational centre (area 39, 40). The patient fails to understand the meaning of the written or spoken words and fails to use the proper words to express his thoughts.II. Motor aphasia:a) Broca's aphasia: It is due to damage of the Broca's area (area 44 & 45). The patient can't express himself by spoken words. The muscle of speech are not paralyzed i.e. can use these muscles in other purposes.b) Agraphia: It is due to damage of the Exner's centre (area 46). The patient can't write or draw, in the same time, the muscles of the hand are not paralyzed i.e. can use these muscles in other purposes.

MUSCLE AND NERVE AS A FUNCTIONAL UNIT

Outline

Nerve FibreNeuro-Muscular JunctionMuscle

NERVE FIBRE

The nerve (or nerve trunk) is composed of a larger number of nerve fibres. Each nerve fibre is an axon covered by a myelin sheath and a Schwann sheath. The nerve is surrounded by a loose connective tissue covering and the bundles of individual nerve fibres within the nerve trunk are enclosed in a sheath of connective tissue.

Function: Conduction of nerve impulses; sensory nerve fibres conduct sensory information from the sensory receptors

to the CNS, while motor nerve fibres conduct motor information from the CNS to the

effector organs

Properties of nerve fibres The nerve fibres are highly specialized to respond to stimuli and to conduct nerve impulses to and from the CNS. Therefore the nerve fibres have the properties of excitability and conductivity.

EXCITABILITYIt is a bioelectric phenomenon by which the nerve fibres can respond to stimuli, and convert these stimuli into nerve impulses. Only nerves, muscles and some glands have plasma membranes capable of responding to stimuli i.e. excitable.

The stimulus is a change in the surrounding environment. According to the type of changes around the nerve fibres, stimuli can be divided into:

1- Electrical stimuli: two types of electric currents used for stimulation of nerve fibres: e.g. a) Galvanic current; It is low in intensity and long in duration, and b) Faradic current; which is high in intensity and short in duration.

2- Chemical stimuli: e.g. Chemical transmitters (acetylcholine, noradrenaline and adrenaline), hormones, drugs, ions (Na+, K+, Ca2+ etc.), gases (O2 and CO2).

3- Physical stimuli: Thermal e.g. cooling or warming. Mechanical e.g. stretch, touch, pressure and injury. Electromagnetic e.g. light rays affecting the retina of the eye.

Factors determining response to Stimulus1 the Effectiveness of the stimulus and 2 the Excitability of the nerve fibres.

The effectiveness of stimulus is determined by: 1) Strength (intensity) of the stimulus: 2) Duration 3) Rate of rise of intensity:

Effectiveness of the stimulus1. Strength (intensity) of the stimulus:

Sub minimal (sub threshold) stimuli: are all stimuli of low intensity which produce no response (even if applied for a very long time).

Minimal (threshold) stimulus: is the weakest stimulus which produces a response. Superminimal (superthreshold) stimuli: Increasing the intensity of the stimulus

gradually above the threshold value leads to gradual increase in the response till it becomes maximum.

Maximal stimulus: is the stimulus which produces a maximal response. When the stimulus reaches a certain value, the response becomes maximum and fixed i.e. there is no further increase in the response with greater intensities.

Supermaximal stimuli: are all stimuli of greater intensities than the maximal stimulus. These stimuli produce the same response as that of the maximal stimulus.

2) Duration: The stimulus to be effective, must act for a certain length of time known as the

excitation time. Within limit, the stronger the stimulus, the shorter is excitation time. The relation between the strength and duration of a stimulus are shown in strength and duration curve (excitability curve). This curve can be obtained by stimulating the nerve with electrical stimuli of different intensities and recording the time needed by each stimulus to start the response.

The chronaxia (time factor): is the time required to stimulate the nerve fibres by a stimulus, which is double the rheobase. It is used to compare the excitability of different tissues. The shorter the chronaxia, the greater the excitability and vice versa.

3) Rate of rise of intensity: The stimulus becomes effective only if the rate of rise exceeds a certain limit. When

the current rise too slowly, the nerve accommodate itself to the presence of the current.

Accommodation means a rise in the threshold of stimulation of the tissues, with the slowly increasing stimuli. To minimize accommodation, the stimulus must rise extremely rapidly.

Nature of excitabilityExcitability is a bioelectric phenomenon in which the nerve fibres respond to stimuli by rapid changes in their resting membrane potential and conduct action potentials along the nerve fibres to their terminals.

Resting membrane potential (RMB):During rest, the nerve fibre spends energy to maintain its state of polarization in which the inner surface of the nerve fibre is negatively charged compared with outer surface which is positively charged. The difference in potential between the inside and outside of the nerve fibres is known as the resting membrane potential. It is about 70mV. and expressed as –70 mV because the inner surface of the plasma membrane is negatively charged relative to the interstitial fluid.

Causes of the resting membrane potential:1) Distribution of ions inside and outside the nerve fibre:2) Selective permeability of the cell membrane:

3) Sodium and potassium pump: (Na+ - k+ pump)

Action Potential

Action potential consists of the electrical changes which occur in the resting membrane potential as a result of stimulation by an effective stimulus. These electrical changes propagate along the nerve fibres to the effector organ producing the response or action (hence the name action potential). The electrical changes of the action potential are: Depolarization and Repolarization

As an action potential travels down the axon, there is a change in polarity across the membrane. The Na+ and K+ gated ion channels open and close as the membrane reaches the threshold potential, in response to a signal from another neuron. At the beginning of the action potential, the Na+ channels open and Na+ moves into the axon, causing depolarization. Repolarization occurs when the K+ channels open and K+ moves out of the axon. This creates a change in polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the axon terminal where it signals other neurons. After passage of an action potential (depolarization and repolarization), the ionic composition inside and outside the cell membrane is slightly disturbed (some Na+ ions go inside during depolarization and some K+ ions go outside during repolarization). Redistribution of Na+ and K+ ions to the normal resting condition is established by the Na–K pump which actively transports sodium out and potassium into the cell.

ACTION POTENTIAL

1. A stimulus is received by the dendrites of a nerve cell. This causes the Na+ channels to open. If the opening is sufficient to drive the interior potential from -70 mV up to -55 mV, the process continues.

2. Having reached the action threshold, more Na+ channels (sometimes called voltage-gated channels) open. The Na+ influx drives the interior of the cell membrane up to about +30 mV. The process to this point is called depolarization.

3. The Na+ channels close and the K+ channels open. Since the K+ channels are much slower to open, the depolarization has time to be completed. Having both Na+ and K+ channels open at the same time would drive the system toward neutrality and prevent the creation of the action potential.

4. With the K+ channels open, the membrane begins to repolarize back toward its rest potential.

5. The repolarization typically overshoots the rest potential to about -90 mV. This is called hyperpolarization and would seem to be counterproductive, but it is actually important in the transmission of information. Hyperpolarization prevents the neuron from receiving another stimulus during this time, or at least raises the threshold for any new stimulus. Part of the importance of hyperpolarization is in preventing any stimulus already sent up an axon from triggering another action potential in the opposite direction. In other words, hyperpolarization assures that the signal is proceeding in one direction.

6. After hyperpolarization, the Na+/K+ pump eventually brings the membrane back to its resting state of -70 mV.

CONDUCTIVITY

Conductivity: Propagation of the action potentialAfter action potential is initiated, it propagates along the axon from the region of the initial segment down to the terminal ending. The action potential must be propagated in order to transfer information from one place in the nervous system to the other.

Propagation is possible because the action potential generated at one site on the axon, acts as a stimulus for the production of another action potential in the adjacent sites of the axon.

A) Propagation in unmyelinated nerve fibres: (Continuous conduction)Stimulation of the nerve fibre by an effective stimulus leads to generation of an action potential at the site of stimulation. During the action potential the stimulated membrane becomes depolarized (membrane potential becomes +35m.v), this creates a potential difference between the depolarized (active) area and the adjacent polarized (resting) area (- 70 m.v). Because of this potential difference local current flows between the two areas causing the polarized (resting) area to become depolarized to the threshold level. This generates an action potential at the resting area, which by turn becomes the stimulus for generating another action potential in the next area along the nerve fibre. This type of conduction (continuous conduction) is relatively slow 0.5-2.0 meter/sec.

B) Propagation in myelinated fibres: (Saltatory conduction):In myelinated nerve fibres, the myelin acts as an electric insulator around the axon except at the nodes of Ranvier, where the membrane of the axon is exposed and contains large number of Na+ and K+ channels. Stimulation of a myelinated nerve

fibre leads to generation of an action potential at the nearest node of Ranvier. During action potential, the first node of Ranvier becomes depolarized, this creates a potential difference between the depolarized (active) and the next polarized (resting) node of Ranvier. Because of this potential difference charges jump from one node to another leading to depolarization of the next polarized node. When this depolarization reaches a threshold level, it leads to generation of an action potential at the resting node and by turn creates a potential difference between it and the adjacent node causing its depolarization and so on. Thus depolarization jumps along the nerve fibre, from one node to another. The greater the distance between nodes of Ranvier, the greater the velocity of conduction of the action potential. This type of conduction is known as saltatory conduction (saltus means jump in Latin). It is faster (may reach up to 120 met/sec) than the step-by-step continuous conduction in unmyelinated fibres.

Effects of stimulation of the nerve fibres

A) Stimulation by an ineffective (sub-minimal) stimuli:This will produce a localized area of depolarization which does not reach the threshold potential or the firing level (-55 mV). So, it is not strong enough to spread along the nerve fibres. The localized area of depolarization is known as “the local excitatory state” which is a type of graded potential. Local excitatory state is characterized by:1. It is localized to the site of stimulation and nearby area.2. During conduction, it decreases gradually with distance till it disappears (conducted with

decrement).3. The magnitude of the local excitatory state is proportional with the strength of the sub-

minimal stimulus i.e. it does not obey the all or none law. Also, it has no threshold.4. Its duration is very short (less than 1 m. sec).5. It can be summated to the local excitatory state of another sub-minimal stimuli. Two

types of summation can occur:a) Spatial summation: By applying several sub-minimal stimuli at the same time at different sites near each other.b) Temporal summation: By applying several sub-minimal stimuli at the same site within a very short time (less than the duration of the local excitatory state) .

6. It is associated with increased excitability because the nerve fibres can respond to sub-minimal stimuli applied at the same time.

7. It has no refractory period.

B) Stimulation by an effective stimulus:This will produce a propagated action potential or a nerve impulse. Nerve impulse is a wave of depolarization which passes along the whole length of the nerve fibre after its stimulation by an effective stimulus (minimal, super-minimal, maximal or super-maximal stimuli).

Properties of the nerve impulse

I. The nerve impulse is a wave:Like any wave, the nerve impulse has a magnitude (strength), duration and velocity of conduction. The magnitude (mV) of the nerve impulse is the magnitude of the spike potential, the duration (m. sec) of the nerve impulse is the duration of the spike potential, and the velocity of the nerve impulse is the velocity of conduction of the nerve fibres.

The wave properties (magnitude, duration and velocity) of the nerve impulse differ according to the type of the nerve fibres.

The nerve fibres are classified into the following type:

Type A fibres: These fibres are thick myelinated fibres. They have the greatest diameter (2-20 m). They conduct impulses with the greatest velocity (10-120met/sec). Type A fibres are subdivided into alpha, beta, gamma and delta fibres. These fibres include somatic sensory fibres (carrying cutaneous and proprioceptive sensation to the CNS) and somatic motor fibres (carrying motor fibres from the CNS to the skeletal muscles). Thus, both sensory (afferent) and motor (efferent) nerves that regulate the activity of the skeletal muscles consist of rapidly conducting type A fibres. The high conduction velocity allows us to avoid dangerous stimuli by withdrawal reflexes.The nerve impulse in type A fibres is high in magnitude and short in duration (0.5-1m.sec). Type A fibres are very sensitive to pressure. Prolonged deep pressure can cause loss of conduction in A fibres, while pain sensation (carried by C fibres) remains intact. This is the cause of sensation of numbness in leg when the edge of the chair compresses the sciatic nerve.

Type B fibres:These fibres are thin myelinated fibres with moderate diameter (1-3 m). These fibres conduct impulses much more slowly than type A fibres (3-15 met/sec). Type B fibres are found in the autonomic nervous system (in pre-ganglionic sympathetic and parasympathetic fibres) which conduct impulses to the smooth muscles of the viscera and to glands.The nerve impulse in type B fibres is moderate in magnitude and moderate in duration (1.2 m. sec). Type B fibres are sensitive to O2 lack.

Type C fibres:These fibres are the smallest and the slowest nerve fibres. They are thin unmyelinated fibres (0.5-1m). They conduct impulses very slowly (0.5-2 meter/sec). Types C fibres are found in the autonomic nervous system (postganglionic fibres) which mediate slow visceral responses and also present in somatic sensory fibres carrying pain sensation (delayed pain). The nerve impulse in type C fibres is low in magnitude and prolonged in duration (2.0 m. sec).Type C fibres are very sensitive to local anesthetics. These drugs cause loss of conduction in C fibres before they affect the A fibres.

Mixed nerve fibres:The mixed nerve is formed of bundles of nerve fibres of different types. The action potentials produced in these fibres are formed of multiple peaks and differ also in velocities of conduction. The action potential in the mixed nerve is called the compound action potential.When all fibres in the mixed nerve are stimulated the action potential in the fast conducting fibres reaches the recording electrodes sooner than the action potential of the slower fibres. Also, the distance between the stimulating and recording electrodes affect the shape of the compound action potential. The longer the distance, the greater is the separation between peaks of the action potential of the fast and slow fibres. The number and size of the peaks of the compound action potential vary with the type of the fibres present in the mixed nerve. It is important to note that the mixed nerve contains more than one types of the nerve fibres, but none of the peripheral nerves contain all types of nerve fibres.

II. The nerve impulse obeys all or none law:The nerve impulse (action potential) either occurs maximally or it does not occur at all, provided that all other conditions remain constant.If a nerve fibre is stimulated by an electrode and the action potential is recorded by other electrode, we observe the following:- All subminimal stimuli do not produce response i.e. no action potentials are generated

and propagated to the recording electrodes.- Minimal (threshold) stimulus produces a maximal response.- Further increase in the intensity of the stimuli (super-minimal, maximal, super-maximal)

do not produce any further increase in the response i.e. the nerve impulses produced in all conditions always maximum and have exactly the same magnitude, duration and velocity of conduction as the nerve impulse produced by the threshold stimulus.

All or none law is applied in the single nerve fibre and not applied in the nerve trunk. As discussed before the nerve trunk (mixed nerve) is formed of many bundles, each bundle is formed of individual nerve fibres. The nerve impulse recorded from the mixed nerve represents the algebraic summation of the action potentials of the individual nerve fibres. These fibres vary in their types (A, B or C) their threshold of stimulation and their distance from the stimulating electrodes (some are superficial i.e. near and others are deep i.e. away from the electrodes).With sub-minimal stimuli, none of the fibres are stimulated and no response occurs. When the stimuli are of threshold intensity, the most excitable fibres are stimulated and a small action potential is recorded. As the intensity of the stimulus increases the magnitude of the action potential shows a proportional increase until the stimulus is strong enough to stimulate all nerve fibres present in the mixed nerve. The stimulus that produces excitation of all fibres is the maximal stimulus, and further increases in the stimuli (super maximal), produce no further increase in the magnitude of the action potential.

Difference between the local excitatory state (graded potential) and the nerve impulse (action potential):

Local excitatory state (Graded potential) Nerve impulse (Action potential)Proportional with the intensity of the stimulus. Obey all or none law.Can be summated. Can’t be summatedHas no threshold. Has a threshold.Not followed by a refractory period. It is followed by a refractory period.Conducted with decrement. Conducted without decrement.May be a depolarization or hyperpolarization Is a depolarization with overshoot.

Changes occurring in the nerve as results of conduction of a nerve impulse:I. Electrical changes:In the form of a spike potential and after potentials (discussed before).

II. Excitability changes: During conduction of a nerve impulse, the excitability of the nerve fibres varies, and it passes in the following phases:a) Temporal rise of excitability is associated with the local response (local depolarization)

in the nerve fibre before firing level.b) Absolute refractory period (ARP): During this period the excitability of the nerve fibre is

completely lost i.e. no other stimulus, no matter how strong, will excite the nerve. It

means that the nerve is absolutely resistant (refractory) to further stimulation. It corresponds to the ascending limb of the spike potential (after the firing level) and the early part of the descending limb (until repolarization is about one-third complete).

Mechanism: During the ascending limb of the spike, the gates of the voltage sensitive Na+ channels are opened. If a second stimulus is applied while the Na+ gates are opened (by the first stimulus), it can not have any effect (the gates are already opened). During the early part of the descending limb, the gates of Na+ channels are closed and cannot be reopened until the membrane is sufficiently repolarized.Significance: The absolute refractory period limits the number of impulses that can be produced and conducted by the nerve fibres.c) Relative refractory period (RRP): During this period the excitability of the nerve is

partially recovered (but still below normal). Stronger stimuli (more than threshold) are needed to excite the nerve. It corresponds to the late part of the descending limb of the spike potential till the start of the negative after potential.

During this period, the gates of K+ channels are opened and the membrane is in the process of repolarization. Strong stimuli can reopen many (not all) of the gates of the Na+ channels which leads to depolarization of the membrane and production of a second action potential. The magnitude of the second action potential is less than normal (not all Na+ gates are opened).d) Supernormal phase of excitability: During this phase, the excitability is above normal

i.e. weaker stimuli (subminimal) can excite the nerve fibres. It corresponds to the negative after potential where the membrane is still partially depolarized.

e) Subnormal phase of excitability: During this phase, the excitability is below normal i.e. stronger stimuli are needed to excite the nerve fibres. It corresponds to the positive after potential where the membrane is hyperpolarized.

III. Metabolic changes:The nerve contains the enzymes responsible for glycolysis, citric acid (Kreb’s) cycle and electron transport (cytochrome oxidase). Thus the nerve can generate and store energy in the form of ATP.During rest the nerve fibre spends energy to maintain its state of polarization. The energy utilized is derived from ATP which is formed from the metabolic reactions inside the nerve fibre.During passage of a nerve impulse, the metabolic reactions are increased to about double the resting state. The increased metabolic reactions is manifested by increase in CO2 production, increase in glucose utilization and increase in heat production.

IV. Thermal changes:The nerve impulse is accompanied by an increase in heat production which appears in two phases:1- Initial heat: A single nerve impulse causes an initial increase in temperature of 0.000001

C. It is due to the generation and propagation of the nerve impulse.2- Delayed heat: It is about 30 times the initial heat and remains for about 30 minutes. The

delayed heat is due to the metabolic reactions needed to reform the ATP utilized during the action potential.

Factors affecting the excitability and conductivity of the nerve fibres

1) Physical factors:Thermal: Warming increases while cooling decreases the excitability by decreasing the metabolic reactions needed for the Na-K pump. Inhibition of Na-K pump leads to accumulation of the Na+ ions inside the nerve fibres which decreases the membrane potential and lastly leads to loss of the resting membrane potential i.e. loss of excitability and conductivity.Mechanical: Deep pressure on the nerve fibres decreases the excitability and conductivity of these fibres.

2) Chemical factors: Local anesthetic drugs as cocaine, novocaine and xylocaine decrease the membrane

permeability to Na+ ions (by blocking the Na+ channels). Thus, depolarization is inhibited and consequently the nerve impulses fail to be generated and conducted.

Ca++ ions: Increased Ca++ ions decreases excitability of the nerve fibres by decreasing the membrane permeability to Na+ ions and increasing the threshold of stimulation. Decreased Ca++ ions increases excitability by increasing Na+ permeability and decreasing the threshold of stimulation.

Na+ ions: Increased Na+ ions increases excitability by facilitating the process of depolarization. Decreased Na+ ions decreases excitability by delaying the process of depolarization.

K+ ions: Increased K+ ions in the extracellular fluid increases excitability because K+ ions diffuse inside the nerve fibre producing depolarization (like Na+ ions). Decreased K+ ions in the extracellular fluid decreases excitability because K+ ions diffuse from inside to outside the nerve fibres producing hyperpolarization.

O2 lack and CO2 excess decreases excitability. H+ ion concentration: Alkalinity increases, while acidity decreases excitability.

3) Electrical factors: In electrotonus (electrotonic potential) the an-electrotonus decreases while the cat-electrotonous increases the excitability. Electrotonus means the excitability changes which occur in the nerve membrane as a result of passage of a constant galvanic current of sub-threshold intensity in the nerve fibres. These changes are:Electrotonus.a) An-electrotonus; means the changes which occur at the region of the anode. The resting

membrane potential increases by addition of more positive charges on the outer surface of the membrane i.e. localized area of hyperpolarization. An-electrotonus is associated with decreased excitability. So, stronger stimuli (more than threshold) are needed to excite the nerve fibres. Strong an-electrotonus can abolish completely the excitability and can cause nerve block.

Cat-electrotonus; means the changes which occur at the region of the cathode. The resting membrane potential decreases by addition of negative charges to the outer surface of the membrane i.e. localized area of depolarization. Cat-electrotonus is associated with increased excitability. So, weaker stimuli (sub-threshold) can excite the nerve fibres.

NEUROMUSCULAR JUNCTION

The skeletal muscle fibres are innervated by large myelinated nerve fibres (A alpha) that originate from the motor neurons located in either the spinal cord or the brain stem. Since the number of fibres in the muscle greatly exceeds the number of fibres in the motor nerve, each nerve fibres branches many times and stimulates a variable number of muscle fibres. Thus, a single motor neuron innervates many muscle fibres. A motor neuron, plus the muscle fibres supplied by it is called a motor unit.

In the muscles which perform fine and delicate movements (e.g. eye muscles) only a few (less than 10) muscle fibres are supplied by one motor neuron, while in muscles used for coarse movements (e.g. gastrocnemius muscle) many muscle fibres (1000-2000) are supplied by a single neuron.

The nerve ending makes a junction called the neuromuscular junction nearly at the middle of the muscle fibre. Normally, each muscle fibre receives innervation from only a single axon terminal, although some muscle fibres (about 2%) have multiple innervations.

Functional anatomy of the neuro-muscular junction Near the surface of the muscle, the motor nerve fibre loses its myelin sheath and

divides into many branches, each branch forms a junction with a single muscle fibre. The terminal branches of the axon are covered only by the cytoplasm and the cell

membrane of the Schwann cells (the neurilemma) which fuses with the muscle membrane (the sarcolemma). The terminal part of the axon lies in a shallow groove on the surface of the muscle fibre.

The axon terminal (presynaptic terminal) contains small vesicles that carry acetylcholine which is the chemical transmitter at the neuromuscular junctions. The presynaptic terminals contain also a large number of mitochondria. These provide the metabolic energy for the synthesis of acetylcholine and also for the Na - K pumping mechanism that are necessary for the recovery process that follow the action potential.

The terminal part of the axon is separated from the muscle plasma membrane by a space known as the synaptic cleft.

The post-synaptic membrane is the plasma membrane of the muscle fibre under the terminal part of the axon; it is called the motor end plate. The surface area of this membrane is greatly increased by the presence of numerous folds of this membrane called the junctional folds.

The post-synaptic membrane contains the receptors for the chemical transmitter acetylcholine (cholinergic receptors). These receptors are complex protein molecules that have a double functions.

Each receptor has a binding site for acetylcholine and also acts as an ion channel. Normally, the receptor is not permeable to ions, but when acetylcholine is attached to the binding sites, Na+ and K+ ions can pass through the chemically activated channels according to their electrochemical gradients.

The membrane of the motor end plate contains also an enzyme called cholinestrase. This enzyme is essential for breaking down the acetylcholine to an inactive form once it has done its action.

Mechanism of neuro-muscular transmission

When a nerve impulse in a motor neuron reaches the axon terminal, it opens the voltage sensitive Ca++ channels, and thus allowing the Ca++ ions to diffuse into the axon terminal. The increase in the intracellular Ca++ ion causes the synaptic vesicles that contain acetylcholine to move towards the membrane, fuse with it, and lastly to rupture and release their content into the synaptic cleft.

Acetylcholine diffuses across the cleft to the postsynaptic membrane (motor end plate) where it combines with the specific binding sites on the receptor. When the binding occurs, the membrane channels becomes permeable to both Na+ and K+ ions at the same time. Because of the differences in electrochemical gradients across the membrane, more Na+ move in, than K+ moves out, producing a local depolarization of motor end plate known as the motor end plate potential.

The end plate potential causes small local currents which depolarize the adjacent muscle plasma membrane to the threshold level for generation of an action potential. This action potential propagates on both sides of the motor end plate to the whole length of the muscle fibre leading to its contraction. After passage of the action potential, the muscle membrane repolarizes and returns to its resting potential

Events of Neuromuscular Junction

1. Propagation of an action potential to a terminal button of motor neuron.2. Opening of voltage-gated Ca2+ channels.3. Entry of Calcium into the terminal button.4. Release of acetylcholine (by exocytosis).5. Diffusion of Ach across the space.6. Binding of Ach to a receptor on motor end plate.

Properties of neuro-muscular transmission

1) One way (unidirectional) conduction: Neuromuscular transmission occurs only from the nerve to the muscle and not in the

opposite direction because the chemical transmitter acetylcholine is present only in the terminal parts of the nerve fibre ( presynaptic terminals) and not in the muscle (postsynaptic membrane) and there is a synaptic cleft in between them.

2) There is a delay in conduction: Electrical recording shows that, there is a delay of about 0.5 m.sec between the nerve

impulse reaching the neuromuscular junction and the action potential generated in muscle.

This delay is due to the time needed for the release of acetylcholine from the presynaptic terminals, its diffusion across the synaptic cleft and its combination with the receptors which open the channels leading to diffusion of ions and depolarization of the motor end plate.

3)Neuro-muscular transmission readily shows fatigue: Fatigue is caused by rapid repeated stimulation of the motor nerve which leads to

depletion of the acetylcholine vesicles. O2 lack facilitates the onset of fatigue because it decreases the metabolic reactions needed to reform acetylcholine.

4) Effect of drugs:A. Drugs which stimulate neuro-muscular transmission

1. By direct action: Acetylcholine (exogenous): It is not used clinically because it is rapidly destroyed by cholinestrase enzyme.

Methacholine, carbacol and nicotine, have the same effect of acetylcholine but they are not destroyed by cholinestrase enzyme or are destroyed very slowly. These drugs produce contraction of the muscles which may persist for many minutes to several hours i.e. produce spasm.2. By indirect action; anti-cholinestrases:

These drugs increase neuro-muscular transmission by inhibiting the action of cholinestrase enzyme which normally destroys acetylcholine after producing its action. Inhibition of cholinestrase enzyme leads to accumulation of acetylcholine at the motor end plate which causes strong and prolonged contraction of the muscle. Anti-cholinestrases are of two types:a) Reversible:

These drugs combine temporarily with cholinestrase enzyme e.g. eserine (physostigmine) and prostigmine (neostigmine). These drugs are used in treatment of a disease known as myasthenia gravis.B) Irreversible:

These chemical substances combine strongly and for a long time with cholinestrase enzyme e.g. di-isoprophyl flurophosphate (DFP). It is a dangerous substance used in war (nerve gas) which kills by producing massive inhibition of the cholinestrase enzyme. This leads to accumulation of acetylcholine causing persistent contraction (spasm) of all muscles including the respiratory muscles. This causes asphyxia and death.

B) Drugs which block neuro-muscular transmission Pre-synaptic block: by inhibiting the release of acetylcholine from the pre-synaptic

terminals. It is produced by: Hemicholiniums, this drug interferes with uptake of choline and therefore

acetylcholine becomes depleted. Botulinum toxin: It is an extremely deadly poison produced by bacteria (clostridium

botutinum) present in spoiled food. The toxin interferes with synthesis or release of acetylcholine. Poisoning with this toxin results in muscle paralysis and death.

Post-synaptic block: by preventing the action of acetylcholine on the motor end plate. It is produced by:

Competitive neuro-muscular blockers (e.g. curare) which combines with the cholinergic receptors in the motor end plate preventing the action of acetylcholine. Anticholinestrases (e.g. prostigmine) can overcome the blocking action of curare.

Depolarizing neuro-muscular blockers(e.g. succinylcholine) which produces initial stimulation of the motor end plate due to depolarization, then blocking by maintaining this state of depolarization. So, it produces initial muscular twitches followed by muscle relaxation.

Neuro-muscular blockers are used clinically to produce muscular relaxation during surgical operation and to reduce movements during electroconvulsion treatment of psychotic patients.

5) Effect of ions: - Ca++ ions help neuro- muscular transmission by causing rupture of the acetylcholine

vesicles. Decrease Ca++ ions near the axon terminal will prevent the release of acetylcholine and therefore decreases transmission.

N.B.: Increased Ca++ ions decreases excitability of the skeletal muscles while decreased Ca++ ions increases the excitability of the skeletal muscles.

- Mg++ ions inhibit neuro-muscular transmission by stabilizing the acetylcholine vesicles. Excess Mg++ ions will prevent the release of acetylcholine and therefore decreases transmission.

- K+ ions have anticurare action on the motor end plate.  

Myasthenia gravis (Severe muscle weakness): It is a disease associated with muscular weakness and extreme fatigue following

moderate exercise. It is due to a failure of neuromuscular transmission. Myasthenia gravis is one of the autoimmune diseases. For unknown reasons, some

people produce antibodies that react with the acetylcholine receptors in the postsynaptic plasma membrane (motor end plate). This immune reaction destroys many of the acetylcholine receptors, and the end plate potential becomes very weak. This means that a muscle action potential will not result from a nerve impulse, and the muscle fails to contract. In this disease extreme effort may be required for even ordinary movements. In extreme cases, even breathing becomes very difficult.

Several kinds of treatment can give patients some symptomatic relief. Anticholinestrase enzyme allow acetylcholine to act for a longer period of time on the remaining receptors and adequate end plate potential can be produced. Unfortunately, the effect is only temporary and the drug must be repeated.

 

MUSCLE PHYSIOLOGY

Introduction

Muscles are machines for converting stored chemical energy into mechanical energy (work) and heat. Muscles constitutes 50% of the body weight (40% skeletal muscles and 10% smooth muscles and cardiac muscle).

There are three types of muscles; skeletal muscles, smooth muscles and cardiac muscle. They differ in structure (histologically) in location (anatomically), in functions (physiologically) and in innervations (neurologically).

Muscle System

The muscular system is the biological system of humans that produces movement. The muscular system, in vertebrates, is controlled through the nervous system, although some muscles, like cardiac muscle, can be completely autonomous. Muscle is contractile tissue and is derived from the mesodermal layer of embryonic germ cells. Its function is to produce force and cause motion, either locomotion or movement within internal organs. Much of muscle contraction occurs without conscious thought and is necessary for survival, like the contraction of the heart or peristalsis, which pushes food through the digestive system. Voluntary muscle contraction is used to move the body and can be finely controlled, such as movements of the finger or gross movements that of the biceps and triceps.

Muscle structure

Muscle is composed of muscle cells (sometimes known as "muscle fibres"). Within the cells are myofibrils; myofibrils contain sarcomeres which are composed of actin and myosin. Individual muscle cells are lined with endomysium. Muscle cells are bound together by perimysium into bundles called fascicles. These bundles are then grouped together to form muscle, and is lined by epimysium. Muscle spindles are distributed throughout the muscles, and provide sensory feedback information to the central nervous system. Skeletal muscle, which involves muscles from the skeletal tissue, is arranged in discrete groups. An example is the biceps brachii. It is connected by tendons to processes of the skeleton. In contrast, smooth muscle occurs at various scales in almost every organ, from the skin (in which it controls erection of body hair) to the blood vessels and digestive tract (in which it controls the calibre of a lumen and peristalsis, respectively).

There are approximately 640 skeletal muscles in the human body. Contrary to popular belief, the number of muscle fibres cannot be increased through exercise; instead the muscle cells

simply get bigger. It is however believed that myofibrils have a limited capacity for growth through hypertrophy and will split if subject to increased demand. There are three basic types of muscles in the body (smooth, cardiac, and skeletal). While they differ in many regards, they all use actin sliding against myosin to create muscle contraction and relaxation. In skeletal muscle, contraction is stimulated at each cell by nervous impulses that release acetylcholine at the neuromuscular junction, creating action potentials along the cell membrane. All skeletal muscle and many smooth muscle contractions are stimulated by the binding of the neurotransmitter acetylcholine. Muscular activity accounts for most of the body's energy consumption. Muscles store energy for their own use in the form of glycogen, which represents about 1% of their mass. Glycogen can be rapidly converted to glucose when more energy is necessary.

Types of Muscles

There are three types of muscles:

Smooth muscle or "involuntary muscle" consists of spindle shaped muscle cells found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels. Smooth muscle cells contain only one nucleus and no striations.

Cardiac muscle is also an "involuntary muscle" but it is striated in structure and appearance. Like smooth muscle, cardiac muscle cells contain only one nucleus. Cardiac muscle is found only within the heart.

Skeletal muscle or "voluntary muscle" is anchored by tendons to the bone and is used to effect skeletal movement such as locomotion. Skeletal muscle cells are multinucleated with the nuclei peripherally located. Skeletal muscle is called 'striated' because of the longitudinally striped appearance under light microscopy. Functions of the skeletal muscle include:

o Support of the bodyo Aids in bone movemento Helps maintain a constant temperature throughout the bodyo Assists with the movement of cardiovascular and lymphatic vessels through

contractionso Protection of internal organs and contributing to joint stability

Cardiac and skeletal muscle are striated in that they contain sarcomere and are packed into highly-regular arrangements of bundles; smooth muscle has neither. Striated muscle is often

used in short, intense bursts, whereas smooth muscle sustains longer or even near-permanent contractions.

Skeletal muscle is further divided into several subtypes:

Type I, slow oxidative, slow twitch, or "red" muscle is dense with capillaries and is rich in mitochondria and myoglobin, giving the muscle tissue its characteristic red color. It can carry more oxygen and sustain aerobic activity.

Type II, fast twitch, muscle has three major kinds that are, in order of increasing contractile speed:

o a) Type IIa, which, like slow muscle, is aerobic, rich in mitochondria and capillaries and appears red.

o b) Type IIx (also known as type IId), which is less dense in mitochondria and myoglobin. This is the fastest muscle type in humans. It can contract more quickly and with a greater amount of force than oxidative muscle, but can sustain only short, anaerobic bursts of activity before muscle contraction becomes painful (often attributed to a build-up of lactic acid). N.B. in some books and articles this muscle in humans was, confusingly, called type IIB

o c) Type IIb, which is anaerobic, glycolytic, "white" muscle that is even less dense in mitochondria and myoglobin. In small animals like rodents or rabbits this is the major fast muscle type, explaining the pale color of their meat.

For most muscles, contraction occurs as a result of conscious effort originating in the brain. The brain sends signals, in the form of action potentials, through the nervous system to the motor neuron that innervates the muscle fibre. However, some muscles (such as the heart) do not contract as a result of conscious effort. These are said to be autonomic. Also, it is not always necessary for the signals to originate from the brain. Reflexes are fast, unconscious muscular reactions that occur due to unexpected physical stimuli. The action potentials for reflexes originate in the spinal cord instead of the brain.

There are three general types of muscle contractions, skeletal muscle contractions, heart muscle contractions, and smooth muscle contractions.

Muscular System Working With Other Body Systems

1. Homeostasis 2. Protection 3. Calcium Metabolism 4. Maintaining Body Temperature

Skeletal Muscle Contractions

Steps of a skeletal muscle contraction:

An action potential reaches the axon of the motor neuron. The action potential activates voltage gated calcium ion channels on the axon, and

calcium rushes in. The calcium causes acetylcholine vesicles in the axon to fuse with the membrane,

releasing the acetylcholine into the cleft between the axon and the motor end plate of the muscle fibre.

The skeletal muscle fibre is excited by large myelinated nerve fibres which attach to the neuromuscular junction. There is one neuromuscular junction for each fibre.

The acetylcholine diffuses across the cleft and binds to nicotinic receptors on the motor end plate, opening channels in the membrane for sodium and potassium. Sodium rushes in, and potassium rushes out. However, because sodium is more permeable, the muscle fibre membrane becomes more positively charged, triggering an action potential.

The action potential on the muscle fibre causes the sarcoplasmic reticulum to release calcium ions(Ca++).

The calcium binds to the troponin present on the thin filaments of the myofibrils. The troponin then allosterically modulates the tropomyosin. Normally the tropomyosin physically obstructs binding sites for cross-bridge; once calcium binds to the troponin, the troponin forces the tropomyosin to move out of the way, unblocking the binding sites.

The cross-bridge (which is already in a ready-state) binds to the newly uncovered binding sites. It then delivers a power stroke.

ATP binds the cross-bridge, forcing it to conform in such a way as to break the actin-myosin bond. Another ATP is split to energize the cross bridge again.

Steps 7 and 8 repeat as long as calcium is present on thin filament. Throughout this process, the calcium is actively pumped back into the sarcoplasmic

reticulum. When no longer present on the thin filament, the tropomyosin changes back to its previous state, so as to block the binding sites again. The cross-bridge then ceases binding to the thin filament, and the contractions cease as well.

Muscle contraction remains as long as Ca++ is abundant in sarcoplasm.

Types of Contractions:

Isometric contraction--muscle does not shorten during contraction and does not require the sliding of myofibrils but muscles are stiff.

Isotonic contraction--inertia is used to move or work. More energy is used by the muscle and contraction lasts longer than isometric contraction. Isotonic muscle contraction is divided into two categories: concentric, where the muscle fibres shorten as the muscle contracts (ie. biceps brachialis on the up phase of a biceps curl); and eccentric, where the muscle fibres lengthen as they contract (ie. biceps brachialis on the down phase of a biceps curl).

Twitch--exciting the nerve to a muscle or by passing electrical stimulus through muscle itself. Some fibres contract quickly while others contract slowly.

Tonic -maintaining postural tone against the force of gravity.

The Efficiency of Muscle Contraction:

Only about 20% of input energy converts into muscular work. The rest of the energy is heat.

50% of energy from food is used in ATP formation. If a muscle contraction is slow or without movement, energy is lost as maintenance

heat. If muscle contraction is rapid, energy is used to overcome friction.

Summation of Muscle Contraction: It is the adding together of individual muscle twitches to make strong muscle movements.

Multiple motor unit summation--increasing number of motor units contracting simultaneously.

Wave summation--increasing rapidity of contraction of individual motor units. Tetanization--higher frequency successive contractions fuse together and cannot be

distinguished from one another.

Sliding Filament theory

When a muscle contracts, the actin is pulled along myosin toward the centre of the sarcomere until the actin and myosin filaments are completely overlapped. The H zone becomes smaller and smaller due to the increasing overlap of actin and myosin filaments, and the muscle shortens. Thus when the muscle is fully contracted, the H zone is no longer visible. Note that the actin and myosin filaments themselves do not change length, but instead slide past each other.

Cellular Action of Skeletal Muscles

During cellular respiration the mitochondria, within skeletal muscle cells, convert glucose from the blood to carbon dioxide and water in the process of producing ATP. ATP is needed for all muscular movement. When the need of ATP in the muscle is higher than the cells can produce with aerobic respiration, the cells will produce extra ATP in a process called anaerobic respiration. The first step of aerobic respiration (glycolysis) produces two ATP per glucose molecule. When the rest of the aerobic respiration pathway is occupied the pyruvate molecule can be converted to lactic acid. This method produces much less ATP than the aerobic method, but it does it faster and allows the muscles to do a bit more than if they relied solely on ATP production from aerobic respiration. The drawback to this method is that lactic acid accumulates and causes the muscles to fatigue. They will eventually stop contracting until the breakdown of lactic acid is sufficient to allow for movement once again. People experience this most noticeably when they repeatedly lift heavy things such as weights or sprint for a long distance. Muscle soreness sometimes occurs after vigorous activity, and is often misunderstood by the general public to be the result of lactic acid build-up. This is a misconception because the muscle does fatigue from lactic acid build-up, but it does not stay in the muscle tissue long enough to cause tissue breakdown or soreness. During heavy breathing, following exercise, the cells are converting the lactic acid either back into glucose or converting it to pyruvate and sending it through the additional steps of aerobic respiration. By the time a person is breathing normally again the lactic acid has been removed. The soreness is actually from small tears in the fibres themselves. After the fibres heal they will increase in size. The number of mitochondria will also increase if there is continued demand for additional ATP. Hence, through exercise the muscles can increase in both strength and endurance.

Another misconception is that as the muscle increases in size it also gains more fibres. This is not true. The fibres themselves increase in size rather than in quantity. The same holds true for adipose tissue--fat cells do not increase in number, but rather the amount of lipids (oil) in the cells increase.

Muscle fibres are also genetically programmed to reach a certain size and stop growing from there, so after a while even the hardest working weightlifter will only reach a certain level of strength and endurance. Some people will get around this by taking steroids. The artificial steroids cause all sorts of trouble for the person. They can cause the adrenal glands to stop producing corticosteroids and glucosteroids. This leads to the atrophy of the gland's medulla and causes permanent loss of the production of these hormones. The testicles may also atrophy in response to steroids. Eventually the testes will stop making testosterone and sperm, rendering the male infertile.

One of the more serious problems associated with abnormal gain of muscle mass is heart failure. While for most people gaining muscle and losing fat is desirable, a body builder is at risk of producing more muscle mass than the heart can handle. One pound of fat contains about 3.5 miles of blood vessels, but one pound of muscle has about 6.5 miles. Hence, additional muscle causes the heart to pump more blood. Some people that have too much muscle will be very strong but will not have a healthy aerobic endurance, in part because of the difficulty of providing oxygenated blood to so much tissue.

Involuntary Muscle Movement

Spasms: When Smooth and skeletal muscles go through multiple spasms it is referred either as seizure or convulsion.

Cramps: Strenuous activities can cause painful spasms that are long, this is referred to as cramps.

Injury

Sprain: An injury to a joint that involves a stretched or torn ligament.

Muscle Strain: A strain occurs when a muscle or the tendon that attaches it to the bone is overstretched or torn. Muscle strains are also called pulled muscles. Muscle strains usually occur during activities that require the muscle to tighten forcefully. The muscle is strained either because it is not properly stretched, or warmed up, before the activity; it is too weak; or because the muscle is already injured and not allowed time to recover. So, many muscle strains occur during exercise or sports activities. They can also occur when lifting heavy objects. What are the symptoms?

When a muscle is strained, it hurts and is difficult to move. You may also feel a burning sensation in the area of the injured muscle, or feel as though something has "popped." Sometimes the area of the strained muscle looks bruised or swells. A strained muscle might spasm, which means it contracts suddenly and involuntarily, causing severe pain. How is it diagnosed?

To diagnose a muscle strain, your doctor will examine the painful area, and ask how and when the injury happened. He or she may order other diagnostic tests, such as x-rays, to rule out any injury to the bone.

Treatment

Muscle strains are treated with rest, ice, compression, and elevation, or RICE. You will be told to rest the injured area to reduce pain and swelling. If the strain is in the leg or foot area, you may need to use crutches. Ice packs are recommended at regular intervals (as recommended by your doctor) over the first few days after the injury. Ice causes the blood vessels to constrict, which reduces inflammation and pain. Anti-inflammatory medications might also be used to relieve pain. Compression and elevation help to reduce swelling. Your doctor may also recommend physical therapy to speed your recovery. You should avoid the type of activity that caused the injury until the muscle is completely healed. Self-care tips

You can prevent muscle strains by warming up for at least 10 minutes before participating in any strenuous exercise or heavy lifting. When you warm up, you increase the blood circulation to the muscle and prepare it for exercise. When starting any new exercise program or sport, it's important to begin gradually so your muscles are conditioned for the activity.

Smooth Muscle Contraction

Contractions are initiated by an influx of calcium which binds to calmodulin. The calcium-calmodulin complex binds to and activates myosin light-chain kinase. Myosin light-chain kinase phosphorylates myosin light-chains using ATP, causing

them to interact with actin filaments. Powerstroke. Calcium is actively pumped out of the cell by receptor regulated channels. A second

messanger, IP3, causes the release. As calcium is removed the calcium-calmodulin complex breaks away from the

myosin light-chain kinase, stopping phosphorylation. Myosin phophatase dephosphorylates the myosin. If the myosin was bound to an actin

molecule, the release is slow, this is called a latch state. In this manner, smooth muscle is able to stay contracted for some time without the use of much ATP. If the myosin was not bound to an actin chain it loses its affinity for actin.

It should be noted that ATP is still needed for crossbridge cycling, and that there is no reserve, such as creatine phosphate, available. Most ATP is created from aerobic metabolism, however anaerobic production may take place in times of low oxygen concentrations.

Cardiac Muscle: Cardiac muscle is found in the heart and lungs of humans

ATP in the Human Body

Muscles cells, like all cells, use ATP as an energy source. The total quantity of ATP in the human body at any one time is about 0.1 Mole. The energy used by human cells requires the hydrolysis of 200 to 300 moles of ATP daily. This means that each ATP molecule is recycled 2000 to 3000 times during a single day. ATP cannot be stored, hence its consumption must closely follow its synthesis. On a per-hour basis, 1 kilogram of ATP is created, processed and then recycled in the body. Looking at it another way, a single cell uses about 10 million ATP molecules per second to meet its metabolic needs, and recycles all of its ATP molecules about every 20-30 seconds.

Lactic Acid

Catabolized carbohydrates is known as glycolysis. The end product of glycolysis, pyruvate can go into different directions depending on aerobic or anaerobic conditions. In aerobic it goes through the Krebs cycle and in anaerobic it goes through the Cori cycle. In the Cori cycle pyruvate is converted to lactate, this forms lactic acid, lactic acid causes muscle fatigue. In the aerobic conditions pyruvate goes through the Krebs cycle. For more about Krebs cycle refer to chapter 2 Cell Physiology.

Muscle Disorders

Dermatomyositis and Polymyositis

Dermatomyositis and polymyositis cause inflammation of the muscles. They are rare disorders, affecting only about one in 100,000 people per year. More women than men are affected. Although the peak age of onset is in the 50s, the disorders can occur at any age.

Signs and symptoms — Patients complain of muscle weakness that usually worsens over several months, though in some cases symptoms come on suddenly. The affected muscles are close to the trunk (as opposed to in the wrists or feet), involving for example the hip, shoulder, or neck muscles. Muscles on both sides of the body are equally affected. In some cases, muscles are sore or tender. Some patients have involvement of the muscles of the pharynx (throat) or the esophagus (the tube leading from the throat to the stomach), causing problems with swallowing. In some cases, this leads to food being misdirected from the esophagus to the lungs, causing severe pneumonia.

In dermatomyositis, there is a rash, though sometimes the rash resolves before muscle problems occur. A number of different types of rash can occur, including rashes on the fingers, the chest and shoulders, or on the upper eyelids (show picture 1-3). In rare cases, the rash of dermatomyositis appears but myopathy never develops.

Other problems sometimes associated with these diseases include fever, weight loss, arthritis, cold-induced color changes in the fingers or toes (Raynaud phenomenon), and heart or lung problems.

Muscle Atrophy

Alternative names : Atrophy of the muscles, Muscle wasting, Wasting

The majority of muscle atrophy in the general population results from disuse. People with sedentary jobs and senior citizens with decreased activity can lose muscle tone and develop significant atrophy. This type of atrophy is reversible with vigorous exercise. Bed-ridden people can undergo significant muscle wasting. Astronauts, free of the gravitational pull of Earth, can develop decreased muscle tone and loss of calcium from their bones following just a few days of weightlessness.

Muscle atrophy resulting from disease rather than disuse is generally one of two types, that resulting from damage to the nerves that supply the muscles, and disease of the muscle itself. Examples of diseases affecting the nerves that control muscles would be poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain-Barre syndrome.

Examples of diseases affecting primarily the muscles would include muscular dystrophy, myotonia congenita, and myotonic dystrophy as well as other congenital, inflammatory or metabolic myopathies.

Even minor muscle atrophy usually results in some loss of mobility or power.

Common Causes

some atrophy that occurs normally with ageing cerebrovascular accident (stroke) spinal cord injury peripheral nerve injury (peripheral neuropathy) other injury prolonged immobilization osteoarthritis rheumatoid arthritis prolonged corticosteroid therapy diabetes (diabetic neuropathy) burns poliomyelitis amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) Guillain-Barre syndrome muscular dystrophy myotonia congenita myotonic dystrophy myopathy

Muscular Dystrophy

Muscular dystrophy (MD) is a group of rare inherited muscle diseases in which muscle fibres are unusually susceptible to damage. Muscles, primarily voluntary muscles, become progressively weaker. In the late stages of muscular dystrophy, muscle fibres are often replaced by fat and connective tissue. In some types of muscular dystrophy, heart muscles, other involuntary muscles and other organs are affected.

The most common types of muscular dystrophy appear to be due to a genetic deficiency of the muscle protein dystrophin. There's no cure for muscular dystrophy, but medications and therapy can slow the course of the disease.

Glossary

ActinA protein that forms a long polymer rods called microfilaments; Interacts with myosin to cause movement in muscles.

ATP"Adenosine Triphosphate" is a nucleotide that comes from adenosine that takes place in muscle tissue: This provides a large source of energy for cellular reactions.

Cardiac muscleis also an "involuntary muscle" but it's a specialized kind of muscle found only within the heart.

Clostridium botulinumA pathogen that causes botulism, gram stain positive, morphology is rod shaped, grows in anaerobic conditions, and produces spores.

Clostridium tetaniA pathogen that causes lock jaw, gram stain positive, morphology is tennis racket shaped rod, grows in anaerobic conditions, and produces spores.

Cori cycleIn anaerobic conditions produces lactic acid.

CrampA localized muscle spasm that happens after strenuous activity.

GlycogenGlucose that has been converted for energy storage. Muscles store energy for their own use in this form.

Lactic acidCauses muscle fatigue.

MuscleContractile tissue that is derived from the mesodermal layer of embryonic germ cells.

Muscular DystrophyA hereditary disease characterized by progressive atrophy of muscle fibres

MyosinThe fibrous motor protein that uses ATP to drive movements along actin filaments.

Sarcoplasmic ReticulumSmooth-surfaced tubules forming a plexus around each myofibril that function as a storage and release area for calcium ions.

Skeletal musclethis "voluntary muscle" is anchored by tendons to the bone and is used to affect skeletal movement such as locomotion.

Smooth musclethis "involuntary muscle" is found within the walls of organs and structures such as the oesophagus, stomach, intestines, bronchi, uterus, ureters, bladder, and blood vessels.

SprainInjuries that involves a stretched or torn ligament.

StrainA injury to the muscle or tendon attachment

charitin; a form of drug use to ensure muscle growth.

HORMONAL AND NEUROENDOCRINE REGULATION

Outline

Introduction to the Endocrine System Hormones The Hypothalamus - Neuro-Endocrine Regulations

Introduction

In order to coordinate the functions of the trillions of cells of the human body, two control systems exist. One, the endocrine system, is a collection of blood-borne messengers that works slowly, while the other, the nervous system, is a rapid control system.

Chemical regulation is by hormones, vitamins, enzymes, ions, gases and chemical transmitters. Chemical regulation is characterized by having a slow onset and prolonged duration of action; chemical regulation controls mainly the metabolic functions of the body. Nervous regulation; by the nervous system: It is characterized by having a rapid onset and a short duration. So, nervous regulation controls the rapid activities of the body.

The endocrine and nervous systems often work toward the same goal. Both influence other cells with chemicals (hormones and neurotransmitters). However, they attain their goals differently. Neurotransmitters act immediately (within milliseconds) on adjacent muscle, gland, or other nervous cells, and their effect is short-lived. In contrast, hormones take longer to produce their intended effect (seconds to days), may affect any cell, nearby or distant, and produce effects that last as long as they remain in the blood, which could be up to several hours.

The two mechanisms are complementary; together they regulate most internal functions and organize and control the activities we know collectively as human behavior. These activities include not only such easily observed acts as smiling and walking but also experiences such as feeling angry, being motivated, having an idea, or remembering a long-past event. Such experiences, which we attribute to the “mind,” are related to the integrated activities of nerve cells in as yet unidentified ways.

INTRODUCTION TO THE ENDOCRINE SYSTEM

Endocrine system is the body’s second great controlling system which influences metabolic activities of cells by means of hormones Endocrine glands includes the pituitary, thyroid, parathyroid, adrenal, pineal, and thymus glands. The pancreas and gonads produce both hormones and exocrine products. Endocrine system are based largely on feedback mechanism; afferent signals are sensed by receptors linked to or on endocrine cells which then release neurotransmitters or hormones which act on the end-organs to restore homeostasis. The immune system and other factors contribute as control factors also, altogether maintaining constant levels of hormones.

The hypothalamus has both neural functions and releases hormones (neuro-endocrine system). Other tissues and organs that produce hormones – adipose cells, pockets of cells in the walls of the small intestine, stomach, kidneys, and heart

The endocrine system provides an electrochemical connection from the hypothalamus of the brain to all the organs that control the body metabolism, growth and development, and reproduction. The endocrine system regulates its hormones through negative feedback (increases in hormone activity decrease the production of that hormone), except in very specific cases like childbirth.

Endocrine Glands

Endocrine Glands are those glands which have no duct and release their secretions directly into the intercellular fluid or into the blood. The collection of endocrine glands make up the endocrine system. The main endocrine glands are the pituitary (anterior and posterior lobes), thyroid, parathyroids, adrenal (cortex and medulla), pancreas and gonads.

The pituitary gland is attached to the hypothalamus of the lower forebrain.

The thyroid gland consists of two lateral masses, connected by a crossbridge, that are attached to the trachea. They are slightly inferior to the larynx.

The parathyroids are four masses of tissue, two embedded posteriorly in each lateral mass of the thyroid gland.

One adrenal gland is located on top of each kidney. The cortex is the outer layer of the adrenal gland. The medulla is the inner core.

The pancreas is along the lower curvature of the stomach, close to where it meets the first region of the small intestine, the duodenum.

The gonads are found in the pelvic cavity.

HORMONES

Hormones, are chemical messengers that enter the blood which carries them from endocrine glands to the cells upon which they act. The cells influenced by a particular hormone are the target cells for that hormone. Hence, a hormone is a chemical messenger produced by a cell that effects specific change in the cellular activity of other cells (target cells).

Endocrine glands secrete their hormones directly into the surrounding extracellular space. The hormones then diffuse into nearby capillaries and are transported throughout the body in the blood. There are two types of hormones secreted in the endocrine system: (1) steroidal and (2) nonsteroidal, or protein based hormones.

Major hormones, their target and their function

Classification of Hormones; Hormones can be chemically classified into four groups:

1. Amino acid-derived: Hormones that are modified amino acids.

2. Polypeptide and proteins: Hormones that are chains of amino acids of less than or more than about 100 amino acids, respectively. Some protein hormones are actually glycoproteins, containing glucose or other carbohydrate groups.

3. Steroids: Hormones that are lipids that are synthesized from cholesterol. Steroids are characterized by four interlocking carbohydrate rings.

4. Eicosanoids: Are lipids that are synthesized from the fatty acid chains of phospholipids found in plasma membrane.

The Endocrine System and Hormonal Functions

Endocrine Gland

Hormone Released Chemical Class

Target Tissue/Organ

Major Function of Hormone

Hypothalamus Hypothalamic releasing and inhibiting hormones

Peptide Anterior pituitary

Regulate anterior pituitary hormone

Posterior Pituitary

Antidiuretic (ADH) Peptide Kidneys Stimulates water reabsorption by kidneys

Posterior Pituitary

Oxytocin Peptide Uterus, mammary glands

Stimulates uterine muscle contractions and release of milk by mammary glands

Anterior Pituitary

Thyroid stimulating (TSH)

Glycoprotein Thyroid Stimulates thyroid

Adrenocorticotropic (ACTH)

Peptide Adrenal cortex Stimulates adrenal cortex

Gonadotropic (FSH, LH)

Glycoprotein Gonads Egg and sperm production, sex hormone production

Prolactin (PRL) Protein Mammary glands

Milk production

Growth (GH) Protein Soft tissue, bones

Cell division, protein synthesis and bone growth

Thyroid Thyroxine (T4) and Triiodothyronie (T3)

Iodinated amino acid

All tissue Increase metabolic rate, regulates growth and development

Calcitonin Peptide Bones, kidneys and intestine

Lowers blood calcium level

Parathyroids Parathyroid (PTH) Peptide Bones, kidneys and intestine

Raises blood calcium level

Adrenal Cortex

Glucocorticoids (cortisol)

Steroid All tissue Raise blood gluclose level, stimulates breakdown of protein

Mineralocoticoids (aldosterone)

Steroid Kidneys Reabsorb sodium and excrete potassium

Sex Hormones Steroid Gonads, skin, muscles and bones

Stimulates reproductive organs and brings on sex characteristics

Adrenal Medulla

Epinephrine and norepinephrine

Modified amino acid

Cardiac and other muscles

Released in emergency situations, raises blood glucose level, “fight or

flight” response

Pancreas Insulin Protein Liver, muscles, adipose tissue

Lowers blood glucose levels, promotes formation of glycogen

Glucagon Protein Liver, muscles, adipose tissue

Raises blood glucose levels

Testes Androgens (testosterone)

Steroid Gonads, skin, muscles and bone

Stimulates male sex characteristics

Ovaries Estrogen and progesterone

Steroid Gonads, skin, muscles and bones

Stimulates female sex characteristics

Thymus Thymosins Peptide T lymphocytes Stimulates production and maturation of T lymphocytes

Pineal Gland Melatonin Modified amino acid

Brain Controls circadian and circannual rhythms, possibly involved in maturation of sexual organs

Mechanism of action of hormone

Hormone produces its action by one of the following mechanisms:

It increases permeability of cell membrane towards a certain substance e.g.:

Insulin increase permeability of the tissue cells to glucose.

ADH increase permeability of the distal tubules and collecting ducts to H2O.

Growth hormone increase transport of AA into cells.

It stimulates the genes of the cells which increase protein synthesis. This leads to increase synthesis of enzymes which in turn increase metabolic reactions inside the cell.

It affects the intra cellular hormone mediators: Some hormones stimulate the formation of cyclic AMP which stimulate most of the intra cellular enzymes, which in turn increase the rate of metabolic reactions.

Types of Hormones

1. General hormones: They act on the whole body e.g. thyroxin, glucocorticoids etc.

2. Local hormones: They act on the same site of their secretion e.g.

Gastro-intestinal hormones which are secreted from the G.I.T and act on the GIT. e.g. gastrin, secretin etc..

Serotonin is formed in the GIT and in brain tissues. It causes local V.C of the injured vessels, increase motility of GIT. It acts as a chemical transmitter in C.N.S and plays a role in producing sleep.

Histamine: is released by all tissues of the body on its damage, also released in cases of allergy from basophils and mast cells.

Histamine produces V.D of arterioles and capillaries, motor to smooth muscles of the bronchioles (as in bronchial asthma) and that of the G.I.T. It also causes secretion of the gastric juice.

Bradykinine: is released from the active tissues. It causes V.D of the B.V of the secretory glands e.g. sweet glands, salivary glands & pancreas.

Hormones essential for life

Essential for life means that in absence of these hormones death will occur e.g.:

Insulin: In absence of insulin body can't utilize glucose but instead utilize fat which leads to the formation of ketone bodies which results in Diabetic acidosis possibly leading Diabetic coma and eventually death.

Parathormone (Parathyroid Hormone): In absence of parathormone serum Ca++ level decreases leading to tetany which affect respiratory muscles which might lead to Asphyxia and eventually Death.

Aldosterone: In absence of aldosterone there is marked Na+ and H2O loss from the body and marked K+ retention. This leads to acidosis, dehydration and muscle weakness which could lead to Death.

NEURO-ENDOCRINE SYSTEM; ROLE OF THE HYPOTHALAMUS

Neuroendocrinology is the study of the interaction between the nervous system and the endocrine system, including the biological features of the cells involved, and how they communicate. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.

The neuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulating reproduction, metabolism, eating and drinking behaviour, energy utilization, osmolarity and blood pressure.

The Hypothalamus

Many of the complex autonomic mechanisms that maintain the chemical constancy and temperature of the internal environment are integrated in the hypothalamus. The hypothalamus also functions with the limbic system as a unit that regulates emotional and instinctual behaviour.

The hypothalamus is the portion of the anterior end of the diencephalon that lies below the hypothalamic sulcus and in front of the interpeduncular nuclei. It is divided into a variety of nuclei and nuclear areas.

Human hypothalamus, with a superimposed diagrammatic representation of the portal hypophysial vessels

Secretion of hypothalamic hormones

Pituitary Gland

Physiologically, it is divided into:

A) Anterior pituitary:

It is the master gland which control the activity of most of the endocrine glands through secretion of the following hormones:

1. T.S.H, which stimulates thyroid gland.

2. ACTH, which stimulates adrenal cortex.

3. Gonadotrophic hormones; F.S.H, L.H, and Prolactin:, which act on male and female gonads (tests and ovary)

4. Growth hormone (GH): It is secreted from alpha cells and has the following actions:

Action of Growth Hormone

On protein Metabolism: It stimulates growth of the whole body by increasing the number & size of cells. It increase protein synthesis and thus it decrease amino acid level in the blood because they are used for protein synthesis.

On carbohydrate Metabolism: It increases Blood glucose level due to decreased glucose uptake and decreased glucose utilization by tissues.

On fat Metabolism: It increases fat mobilization from its stores which increases fatty acids in blood. It also increase fat utilization to produce energy.

On bone growth: It stimulates bone growth through stimulation of osteoblastic activity. GH produces this action indirectly; it stimulates formation of a substance called "Somatomedine" in the liver and kidney. Somatomedine acts on the bones and stimulate its growth.

B) Posterior pituitary:

It contains no secretory cells but contains only terminal nerve ending coming from the Supra-optic and Para-ventricular nuclei of the hypothalamus. Hypothalamic neurons secret two hormones (ADH & Oxytocin). These hormones are carried by hypothalamo-hypophysial tract to be stored in the posterior pituitary.

(I) Anti Diuretic Hormone (ADH):

In case of dehydration the osmotic pressure increases, this stimulates the osmo-receptors present in the hypothalamus. This in turn stimulates secretion of ADH which causes increase permeability of the distal tubules and collecting ducts of the kidney to water. So, it decreases urine volume and preserve water.

(II) Oxytocin Hormone: It has the following actions:

In female:

1. On the mammary glands: It helps milk ejection from the milk acini because it produce contraction of the myo-epthelial cells around these acini. It helps milk secretion (indirectly) through stimulation of secretion of prolactin from the anterior pituitary.

2. On uterus: It stimulates uterine contraction which produce the following:

- Delivery at end of pregnancy and helps in prevention of post-partum haemorrhage. Also it helps the uterus to return to its original size after delivery.

- It helps female to reach orgasm (maximum sexual feeling).

- It helps sucking of sperms at end of coitus which increase fertilization.

In male: It moves sperms from seminiferous tubules and epididymis to vas deferens.

Summary of principal hypothalamic regulatory mechanisms

INHERITANCE, GENES AND DISEASES(INTRODUCTION TO GENETICS AND HEREDITY)

Outline

DNA Genes Inheritance Genetic Disorders

Introduction

Genetics is the science of the way traits are passed from parent to offspring. For all forms of life, continuity of the species depends upon the genetic code being passed from parent to offspring. Genetics is very important in human physiology because all attributes of the human body are affected by a person’s genetic code. It can be as simple as eye colour, height, or hair colour. Or it can be as complex as how well your liver processes toxins, whether you will be prone to heart disease or breast cancer, and whether you will be colour blind. Defects in the genetic code can be tragic. For example: Down Syndrome, Turner Syndrome, and Klinefelter's Syndrome are diseases caused by chromosomal abnormalities. Cystic fibrosis is caused by a single change in the genetic sequence.

Genetic inheritance begins at the time of conception. Offspring inherit 23 chromosomes from the mother and 23 from the father. Together they form 22 pairs of autosomal chromosomes and a pair of sex chromosomes (either XX for female, or XY for male).

Homologous chromosomes have the same genes in the same positions, but may have different alleles (varieties) of those genes. There can be many alleles of a gene within a population, but an individual within that population only has two copies, and can be homozygous (both copies the same) or heterozygous (the two copies are different) for any given gene.

Genetics is important to medicine; as more is understood about how genetics affects certain defects and diseases, cures and treatments can be more readily developed for these disorders.

Karyotype of a Normal Human Male

The DNA (Deoxyribonucleic Acid)

Deoxyribonucleic acid (DNA) is the macromolecule that stores the information necessary to build structural and functional cellular components. It also provides the basis for inheritance when DNA is passed from parent to offspring. The union of these concepts about DNA allows us to devise a working definition of a gene. A gene is a segment of DNA that codes for the synthesis of a protein and acts as a unit of inheritance that can be transmitted from generation to generation.

The external appearance (phenotype) of an organism is determined to a large extent by the genes it inherits (genotype). Thus, one can begin to see how variation at the DNA level can cause variation at the level of the entire organism. These concepts form the basis of genetics and evolutionary theory.

DNA Structure.

(a) The “twisted ladder” structure. The two sugar-phosphate backbones twine around each other while complementary bases (coloured bars) face each other on the inside of the double helix.

(b) A small segment of DNA showing the composition of the backbone and complementary pairing of the nitrogenous bases.

(c) A molecular space-filling model of DNA giving some impression of its actual geometry

Gene

A gene is made up of short sections of DNA which are contained on a chromosome within the nucleus of a cell. Genes control the development and function of all organs and all working systems in the body. A gene has a certain influence on how the cell works; the same gene in many different cells determines a certain physical or biochemical feature of the whole body (e.g. eye colour or reproductive functions). All human cells hold approximately 30,000 different genes.

Genotype is the actual pair of genes that a person has for a trait of interest. For example, a woman could be a carrier for haemophilia by having one normal copy of the gene for a particular clotting protein and one defective copy.

A Phenotype is the organism’s physical appearance as it relates to a certain trait. In the case of the woman carrier, her phenotype is normal (because the normal copy of the gene is dominant to the defective copy). The phenotype can be for any measurable trait, such as eye colour, finger length, height, physiological traits like the ability to pump calcium ions from mucosal cells, behavioural traits like smiles, and biochemical traits like blood types and cholesterol levels.

Genes encode the information necessary for synthesizing the amino-acid sequences in proteins, which in turn play a large role in determining the final phenotype, or physical appearance of the organism.In diploid organisms, a dominant allele on one chromosome will mask the expression of a recessive allele on the other. While most genes are dominant/recessive, others may be codominant or show different patterns of expression.

The phrase "to code for" is often used to mean a gene contains the instructions about a particular protein, (as in the gene codes for the protein). The "one gene, one protein" concept is now known to be the simplistic. For example, a single gene may produce multiple products, depending on how its transcription is regulated. Genes code for the nucleotide sequence in mRNA and rRNA, required for protein synthesis.

Transcription and Translation

Transcription is the process of making RNA. In response to an enzyme RNA polymerase breaks the hydrogen bonds of the gene. A gene is a segment of DNA which contains the information for making a protein. As it breaks the hydrogen bonds it begins to move down the gene. Next the RNA polymerase will line up the nucleotides so they are complementary. Some types of RNA will leave the nucleus and perform a specific function.

Translation is the synthesis of the protein on the ribosome as the mRNA moves across the ribosome. There are eleven basic steps to translation:

1. The mRNA base sequence determines the order of assembling of the amino acids to form specific proteins.

2. Transcription occurs in the nucleus, and once you have completed transcription the mRNA will leave the nucleus, and go into the cytoplasm where the mRNA will bind to a free floating ribosome, where it will attach to a small ribosomal subunit.

3. Methionine-tRNA binds to the nucleotides AUG. AUG is known as the start codon and is found at the beginning of each mRNA.

4. The complex then binds to a large ribosomal subunit. Methionine-tRNA is bound to the P site of the ribosome.

5. Another tRNA containing a second amino acid (lysine) binds to the second amino acid. Binding to the second condon of mRNA (on the A-site of the ribosome).

6. Peptidyl transferase, forms a peptide3 bond between the two amino acids (methionine and lysine)

In summary, the process of protein synthesis as DNA→mRNA→protein, with each arrow reading as “codes for the production of.” The step from DNA to mRNA is called transcription, and the step from mRNA to protein is called translation. Transcription occurs in the nucleus, where the DNA is, and most translation occurs in the cytoplasm. Recent research has shown,

7. The first amino tRNA is released and mRNA is translocated one codon carrying the second tRNA (still carrying the two amino acids) to the P site.

8. Another tRNA with attached amino acid (glutamine) moves into the A site and binds to that codon.

9. It will now form a peptide bond with lysine and glutamine

10. Now the tRNA in the P site will be let go, and mRNA is translocated one codon, (the tRNA with three amino acids) to the P site.

11. This will continue going until it reaches the stop codon (UAG) on the mRNA. Then this codon will tell it to release the polypeptide chain.

Introduction to Heredity

Gregor Mendel researched principals of heredity in plants. He soon realized that these principals also apply to people and animals and are the same for all living animals. He experimented with common pea plants. Over generations of the pea plants, he noticed that certain traits can show up in offspring without blending any of the parent's characteristics. This is a very important observation because at this point the theory was that inherited traits blend from one generation to another.

Mendelian Inheritance

Law Definition

Law of segregation During gamete formation, the alleles for each gene segregate from each other so that each gamete carries one allele for each gene

Law of independent assortment

Genes from different traits can segregate independently during the formation of genes

Law of dominance Some alleles are dominant while others are recessive; an organism with at least one dominant allele will display the effect of the dominant allele

Inheritance

Children inherit traits, disorders, and characteristics from their parents. Children tend to resemble their parents especially in physical appearance. However they may also have the

same mannerisms, personality, and a lot of the time the same mental abilities or disabilities. Many negatives and positives tend to "run in the family".

Children may have the same habits (good or bad) as their parents, like biting their nails or enjoying reading books. These things aren't inherited they are happening because children imitate their parents, they want to be like mom or dad. Good examples are just as important as good genes.

Patterns of Inheritance

Inheritance Pattern Description Examples

Autosomal dominant

Only one mutated copy of the gene is needed for a person to be affected by an autosomal

dominant disorder. Each affected person usually has one affected parent. There is a

50% chance that a child will inherit the mutated gene. Many disease conditions that

are autosomal dominant have low penetrance, which means that although only one mutated copy is needed, a relatively small proportion of those who inherit that mutation go on to

develop the disease, often later in life.

Huntington's disease, Neurofibromatosis 1,

HBOC syndrome, Hereditary

nonpolyposis colorectal cancer

Autosomal recessive

Two copies of the gene must be mutated for a person to be affected by an autosomal

recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are

referred to as carriers). Two unaffected people who each carry one copy of the mutated gene have a 25% chance with each pregnancy of

having a child affected by the disorder.

Cystic fibrosis, Sickle cell anaemia, Tay-

Sachs disease, Spinal muscular atrophy,

Muscular dystrophy

X-linked dominant

X-linked dominant disorders are caused by mutations in genes on the X chromosome. Only a few disorders have this inheritance

pattern. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. The sons of a man with an

X-linked dominant disorder will not be affected, and his daughters will all inherit the

condition. A woman with an X-linked dominant disorder has a 50% chance of

having an affected daughter or son with each pregnancy. Some X-linked dominant

conditions, such as Aicardi Syndrome, are fatal to boys, therefore only girls have them

(and boys with Klinefelter Syndrome).

Hypophosphatemia, Aicardi Syndrome

X-linked X-linked recessive disorders are also caused Haemophilia A,

recessive

by mutations in genes on the X chromosome. Males are more frequently affected than

females, and the chance of passing on the disorder differs between men and women.

The sons of a man with an X-linked recessive disorder will not be affected, and his

daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50% chance of having daughters who

carry one copy of the mutated gene.

Duchenne muscular dystrophy, Colour blindness, Turner

Syndrome

Y-linked

Y-linked disorders are caused by mutations on the Y chromosome. Only males can get them,

and all of the sons of an affected father are affected. Since the Y chromosome is very

small, Y-linked disorders only cause infertility, and may be circumvented with the

help of some fertility treatments.

Male Infertility

Mitochondrial

This type of inheritance, also known as maternal inheritance, applies to genes in

mitochondrial DNA. Because only egg cells contribute mitochondria to the developing

embryo, only females can pass on mitochondrial conditions to their children.

Leber's Hereditary Optic Neuropathy

(LHON)

Mechanisms of Inheritance

A person's cells hold the exact genes that originated from the sperm and egg of his parents at the time of conception. The genes of a cell are formed into long strands of DNA. Most of the genes that control characteristic are in pairs, one gene from mother and one gene from father.

Humans have 22 pairs of chromosomes (autosomes) and two more genes called sex-linked chromosomes. Females have two X (XX) chromosomes and males have an X and a Y (XY) chromosome. Inherited traits and disorders can be divided into three categories:

1. unifactorial inheritance, 2. sex-linked inheritance, and 3. multifactor inheritance

Unifactorial Inheritance

Traits such as blood type, eye colour, hair colour, and taste are each thought to be controlled by a single pair of genes. The genes deciding a single trait may have several forms (alleles). For example, the gene responsible for hair colour has two main alleles: red and brown. The four possibilities are thus:

i. Brown/red, which would result in brown hair, ii. Red/red, resulting in red hair,

iii. Brown/brown, resulting in brown hair, or iv. Red/brown, resulting in red hair.

The genetic codes for red and brown can be either dominant or recessive. In any case, the dominant gene overrides the recessive.For example, if dad has brown/red he has a 50% chance of passing brown hair to his child and a 50% of passing red hair. When combined with a mom who has brown/brown (who would supply 100% brown), the child has a 75% chance of having brown hair and a 25% chance of having red hair. Similar rules apply to different traits and characteristics, though they are usually far more complex.

Unifactorial inheritance

Multifactorial inheritance

Some traits are found to be determined by genes and environmental effects. Height for example seems to be controlled by multiple genes, some are "tall" genes and some are "short" genes. A child may inherit all the "tall" genes from both parents and will end up taller than both parents. Or the child my inherit all the "short" genes and be the shortest in the family. More often than not the child inherits both "tall" and "short" genes and ends up about the same height as the rest of the family. Good diet and exercise can help a person with "short" genes end up attaining an average height.

Babies born with drug addiction or alcohol addiction are a sad example of environmental inheritance. When mom is doing drugs or drinking, everything that she takes the baby takes. These babies often have developmental problems and learning disabilities. A baby born with

Foetal alcohol syndrome is usually abnormally short, has small eyes and a small jaw, may have heart defects, a cleft lip and palate, may suck poorly, sleep poorly, and be irritable. About one fifth of the babies born with foetal alcohol syndrome die within the first weeks of life, those that live are often mentally and physically handicapped.

Sex-linked Inheritance

Sex-linked inheritance is quite obvious, it determines gender. Male gender is caused by the Y chromosome which is only found in males and is inherited from their fathers. The genes on the Y chromosomes direct the development of the male sex organs. The X chromosome is not as closely related to the female sex because it is contained in both males and females. Males have a single X and females have double XX. The X chromosome is to regulate regular development and it seems that the Y is added just for the male genitalia. When there is a default with the X chromosomes in males it is almost always persistent because there is not the extra X chromosome that females have to counteract the problem. Certain traits like colour-blindness and haemophilia are on alleles carried on the X chromosome. For example if a woman is colour-blind all of her sons will be colour-blind. Whereas all of her daughters will be carriers for colour-blindness.

GENETIC DISORDERS

Any disorder caused totally or in part by a fault (or faults) of the genetic material passed from parent to child is considered a genetic disorder. The genes for many of these disorders are passed from one generation to the next, and children born with a heritable genetic disorder often have one or more extended family members with the same disorder.

Inherited Genetic Disease

Some of the most common inherited diseases are hemochromatosis, cystic fibrosis, sickle cell anaemia and haemophilia. They are all passed along from the parents and even if the parents don't show signs of the disease they may be carriers which mean that all of the children they have may be born with the disease.

Non-heritable Genetic Disorders

These are genetic disorders that appear due to spontaneous faults in the genetic material, in which case a child is born with a disorder with no apparent family history.

Down Syndrome, also known as Trisomy 21, is a chromosome abnormality that effects one out of every 800-1000 newborn babies. During anaphase II of meiosis the sister chromatids of chromosome 21 fail to separate, resulting in an egg with an extra chromosome, and a foetus with three copies (trisomy) of this chromosome.

Mutant Genes

Mutation is a permanent change in a segment of DNA. Mutations are changes in the genetic material of the cell. Substances that can cause genetic mutations are called mutagen agents. Mutagen agents can be anything from radiation from x-rays, the sun, toxins in the earth, air, and water viruses. Many gene mutations are completely harmless since they do not change the amino acid sequence of the protein the gene codes for.

Mutations can be good, bad, or indifferent. They can be good for you because their mutation can be better and stronger than the original. They can be bad because it might take away the survival of the organism. However, most of the time, they are indifferent because the mutation is no different than the original.

The not so harmless ones can lead to cancer, birth defects, and inherited diseases. Mutations usually happen at the time of cell division. When the cell divides, one cell contracts a defect, which is then passed down to each cell as they continue to divide.

Teratogens

Teratogens refer to any environmental agent that causes damage during the prenatal period. Examples of Common Teratogens:

drugs: prescription, non-prescription, and illegal drugs

tobacco, alcohol, radiation, environmental pollution, infectious disease, STD's, AIDS, Parasites,

Sensitive period to teratogen exposure, in the embryonic period is most vital. Fetal damage is minor.

Glossary

chromosome

Autosome: chromosome that is not a sex chromosome

Chromosome: threadlike strand of DNA and associated proteins in the nucleus of cells that carries the genes and functions in the transmission of heredity information

Cystic Fibrosis: recessive genetic disorder affecting the mucus lining of the lungs, leading to breathing problems and other difficulties

Fetal Alcohol Syndrome: combination of birth defects resulting form high (sometimes low) alcohol consumption by the mother during pregnancy

Gene: is a segment of nucleic acid that contains the information necessary to produce a functional product, usually a protein.

Genetics: is the science of genes, heredity, and the variation of organisms.

Genome: complete set of genetic information of an organism including DNA and RNA

Genotype: actual set of genes an organism has. It is the blue print of gentic material.

Hemochromatosis: metabolic disorder that causes increased absorption of iron, which is deposited in the body tissues and organs; the iron accumulates in the body where it may become toxic and causes damage

Hemoglobin: component of red blood cells that carries oxygen

Hemophilia: group of heredity disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots

Inheritance: characteristics given to a child by a parent

Modifying Gene: alters how other genes are expressed in the phenotype

Multifactorial Inheritance: trait or disorder determined by multiple genes and/or environmental effects

Phenotype: organisms physical appearance

Polygenic: trait whose expression is influenced by more than one gene

Regulator Genes: initiate or block the expression of other genes.

Sex-linked: pertaining to a trait of a disorder determined by the sex chromosome in a persons cells or by the genes carried on those chromosomes

Sickle Cell Anemia: recessive disorder in which red blood cells take on an unusual shape, leading to other problems with the blood

Synthesize: to make using biochemical processes

Unifactorial Inheritance: trait or disorder determined by a single pair of genes

Zygote: cell formed by the union of male and female gametes. A Zygote is a cell that is the result of fertilization.

REFERENCES

1. Human Physiology: The Basis of Medicine, by Pocock and Richards, (2006)2. Human Physiology by Wikibook Contributors 20073. Medical Physiology Notes (Neurophysiology and Endocrine Systems) by Gad El -

Mawla A. Gad. King Saud University4. Arthur C. Guyton, John E. Hall: Textbook of Medical Physiology 11 th Edition

(2006) 5. Barret et al.: Ganong’s Review of Medical Physiology 23rd Edition (2010)