NERVOUS SYSTEM Handout NRS 25 PDF

NERVOUS SYSTEM NER 202 Page | 0  Index Topics Pg Introduction of nervous system 1. Histological structure of Neurons 2 2. Nerve fibers, th...

NERVOUS SYSTEM NER 202 Page | 0  Index Topics Pg Introduction of nervous system 1. Histological structure of Neurons 2 2. Nerve fibers, their covering. 4 3. Peripheral nerve system 5 4. Degeneration & regeneration of nervous tissue 7 5. Ganglia & Neuroglia. 8 6. Synapse. 9 7. Organization of Neurons in Neuronal pool. 15 8. Skin. 17 9. Nerve endings 23 10. Sensory receptors. 26 11. Somatic sensations. 28 12. Cranial nerves. 33 13. Embryological Preview 43 Central nervous system 14. Anatomy of spinal cord & Lamination. 47 15. Brain stem 51 16. Cerebrum. 55 17. The reflexes. 60 18. Tracts of spinal cord: Cortical ascending tracts 67 71 Short tracts 72 Sub-cortical ascending tracts & Pathways from face & head 19. Lesions of sensory system. 73 20. Pain sensation 75 21. Headache 80 22. RAS. 81 23. Descending tracts (Motor). 84 24. Motor cortex. 86 25. Spinal cord lesions. 88 26. Basal ganglia. 90 27. Cerebellum 93 28. Ataxia. 97 29. Anatomy of meninges & Dural folds, 101 30. Anatomy of Ventricular system & CSF. 103 31. Arterial blood supply of CNS 105 32. Venous drainage of CNS 107 33. Brain barriers 108 Page | 1  Nervous tissue ❖ Structurally, nervous tissue consists of two cell types: nerve cells (neurons) and glial cells. Neurons ❖ Definition: The structural and functional unit of the nervous system, constitute more than 100 million cells. ❖ Histological Structure: Most of neurons consist of 2 parts; A- Cell body (Perikaryon): is a part of the neuron receptive to stimuli and is containing nucleus and surrounding cytoplasm. - Size: varies from 4µm as in granular cells in cerebellar cortex to 100µm as inmotor neurons in spinal cord. - Shape: depends on the number of cells processes; Unipolar has globular shape, Bipolar have fusiform shape Multipolar are stellate, pyramidal or pyriform. a) The nucleus: - It is usually large spherical, euchromatic with a prominent nucleolus reflecting the intense synthetic activity of these cells. b) The cytoplasm: 1- It contains highly developed rough endoplasmic reticulum and numerous polyribosomes suggesting that these cells synthesize both structural proteins and proteins for transport. When stained, rER, free ribosomes and polysomes appear under the light microscope as basophilic granular areas called Nissl bodies. Their number varies according to neuronal type & functional state. 2- The Golgi complex is present around the nucleus. 3- Mitochondria 4- Neurofilaments: intermediate filaments with diameter of 10nm) are abundant in Perikaryon and processes. They bundle together as a result of the action of fixatives to form neurofibrils (2 µm in diameter) that are visible by the light microscope (stained brown by Ag). They provide structural support. 5- Microtubules (20-28 nm in diameter) are arranged in parallel bundles in perikaryon and processes. They are involved in axonal transport of neurotransmitter substances, enzymes and other cellular constituents. 6- Centrioles are not seen as neurons cannot divide. 7- Inclusions in form of: Lipofuscin pigment which is golden brown. It is a residue of undigested materialby lysosomes. Its amount increases with aging. Page | 2  Melanin pigment which is dark brown or black. It is found in neurons of thesubstantia nigra of the mid brain. Lipid droplets in cytoplasm as energy reserve or products of abnormal metabolism. B- The processes: - Dendrites are multiple processes that receive stimuli from the environment or other neurons and carry it to the cell body. - Axon is a single process that conveys information away from the cell body to other neurons or effector cells as the muscle cell. - Both the dendrites and axon have mitochondria, neurofibrils and microtubules Dendrites Axon 1- Usually numerous 1- Single originates from axon Hillock 2- Short. 2- Long. 3- Thick. 3- Thin. 4- Branching like a tree. Branches arise at 4- Not branching except at the end. It may give acute angle. collateral branchesnear the cell body that arise at right angle 5- Become thinner & they are ssubdivide 5- Has a constant diameter into branches. 6- Contain Nissl bodies 6- Does not contain Nissl granules. ❖ Classification of neurons: A. -They are classified according to number of processes into: 1- Unipolar: have a single process that is close to the Perikaryon and divides into 2 branches to form a T shape, with one branch extending to peripheral ending to act functionally as a dendrite but its structure is similar to that of axon and the other towards the central nervous system to represent the axon. The stimuli that are picked by the dendrites travel directly to the axon without passing through the Perikaryon. It is found in the spinal ganglia and mesencephalic nucleus of trigeminal nerve. 2- Bipolar: have one dendrite and one axon. This type is present in cochlear and vestibular ganglia in ear, retina in eye and the olfactory mucosa. Page | 3  3- Multipolar: have one axon and many dendrites. They take different forms: a- Stellate as the anterior horn cells in spinal cord. b- Pyramidal as pyramidal cells in cerebral cortex. c- Pyriform as Purkinje cells in cerebellar cortex. B. According to function: 1- Sensory (Efferent) neurons receive sensory stimuli as cells of dorsal root ganglion. 2- Motor (afferent) neurons control effector organs such as muscles andglands as anterior horn cells in spinal cord. 3- Interneurons connect neurons in retina and spinal cord. C. According to length of axon: 1- Golgi type 1: neurons have long axon that leaves the grey matter and enters white matter as motor neurons in spinal cord, pyramidal cells in cerebral cortex and Purkinje cells in cerebellar cortex. 2- Golgi type 2: neurons have short axon that does not leave the grey matter as in interneurons in cerebral and cerebellar cortex. Nerve fiber and their covering ❖Nerve fibers: consists of an axon covered by axolemma and contains axoplasm cytoplasm). It arises from a conical extension of cell body called axon hillock. ❖Types of nerve fibers: 1- Unmyelinated nerve fibers: have no myelin sheath and is divided into: a- Unmyelinated fibers without sheath of Schwann cells (neurolemma) as in gray matter (Naked). b- Unmyelinated nerve fibers with sheath of Schwann cells as in sympathetic post ganglionic fibers. 2- Myelinated nerve fibers: have myelin sheath and is divided into: a- Myelinated nerve fibers without sheath of Schwann cells as in white matter. b- Myelinated nerve fibers with sheath of Schwann cells as in peripheral nerve fibers. ❖The sheath of Schwann (Neurolemmal sheath) It consists of flattened cells with flattened nuclei called Schwann cells that form thin chain around the myelin of a nerve fiber. Functions: 1) Formation of myelin sheath in the peripheral nerves. 2) Electric insulation. 3) Regeneration where axon grows from the proximal stump formed by Schwann cells. ❖ Myelin Sheath: Formation: It is formed by rotation of Schwann cells (in peripheral nervous system) or Oligodendroglia processes (in central nervous system) around the axon several Page | 4  turns. Each Schwann cell wraps around one segment of a single axon. while each oligodendroglia cell warps around one or more segments of many axons (10-60). Structure: It is made of many layers of modified cell membranes with a higher proportion of lipids than other cell membranes. LM: After routine fixation Lipoprotein dissolves. It can be stained black with osmic acid. E/M: It appears as fused spiral laminae of plasmalemma. It shows gaps called nodes of Ranvier that represent the spaces between adjacent sheath cells. The sheath of myelin is thus divided into segments by the nodes which are called internodal segments. Functions: enhances the speed of nerve impulse. Stages of myelination (Formation of myelin sheath): 1. Axon invaginates into near sheath cell (Schwann cell in peripheral nervous system or oligodendroglia in central nervous system). 2. Further invagination so axon is surrounded by a single turn of cell membrane. 3. The single turn progresses into many turns (up to 50 turns) in a spiral form mostly due to rotation of the sheath cell. 4. The intervening cytoplasm is pushed to the cell body leading to compaction of the turns. 5. Fusion of cell membranes of the spirally arranged turns to form myelin sheath. Diagram showing steps of myelin sheath formation by Schwann cells Peripheral Nervous System It consists of Nerves, ganglia and nerve endings. Peripheral Nerve ❖Definition: Bundles of nerve fibers held together by connective tissue. The nerve is covered by dense connective tissue called epineurium. Nerve bundles are surrounded by perineurium. It is formed of flattened epithelium- like cells joined by tight junctions. This forms a barrier to protectthe nerve fibers. Page | 5  Inside the bundle the nerve fibers are connected by endoneurium (sheath of Henle). It consists of reticular fibers formed by Schwann cells. Diagram showing structure of peripheral nerve ❖In histological preparations, the appearance of nerve fibers depends on the stain: 1. Preparations stained by H & E., the lipid component of myelin have been dissolved during dehydration, leaving behind central faintly stained axon. 2. Preparations stained by osmic acid, the lipid component is preserved andappears as black ring around the site of the axon. Diagram showing nerve trunk stained Diagram showing nerve trunk stained with H&E with osmic acid Page | 6  Degeneration and regeneration of nerve tissue - In a wounded nerve fiber, there are two distinct types of changes: A- Retrograde degeneration (Traumatic degeneration): In nerve cell and proximal part of nerve fiber Chromatolysis: disappearance of Nissl bodies with decrease in basophilia. Increase in volume of Perikaryon with loss of dendrites so becomes globular. Migration of nucleus to peripheral position. Disappearance of Golgi body and mitochondria. Fragmentation of neurofibrils. Lysosomes increase B- Wallerian degeneration: in distal part of nerve fiber. a. Axon: neurofibrils appear beaded, then segmented, then granular and finally disappear. b. Myelin sheath shows widening of nodes of Ranvier. The internodal segments are termed fermentation chambers as fat split into fatty acids. c. Schwann cells proliferate giving rise to cellular columns that act as guide for the growing axons during regeneration. ❖Stains of degeneration: 1. Silver: to demonstrate changes in Golgi body and Neurofibrils. 2. Osmic acid: to demonstrate changes in myelin sheath. 3. Basic stains: to demonstrate changes in Nissl bodies. ❖Regeneration takes place where; 1. Macrophages remove debris and secrete interleukin 1 (substances secreted by cells of the immune system) which stimulates Schwann cells to secrete substances that promote nerve growth. 2. Growth of axons in proximal part in direction of the columns of Schwann cells. Regeneration is efficient when the fibers and the columns of Schwann cells are directed to the correct place. Diagram showing steps of nerve fibers regeneration Page | 7  Ganglia Definition: collection of nerve cells and glial cells outside CNS supported byconnective tissue. Types: Craniospinal and autonomic (sympathetic or parasympathetic). Spinal ganglion Sympathetic 1. Covered by thick connective tissue 1. Covered by thin connective capsule. tissue capsule. 2. Blood vessels are less. 2. Blood vessels are more. 3. Cells are arranged in groups or 3. Cells are scattered rows. 4. Cells are variable in size. 4. Cells are uniform in size. 5. Cells are larger. 5. Cells are smaller. 6. Cells are unipolar 6. Cells are stellate multipolar. 7. Cells have glomeruli formed by 7. No glomeruli. coiling of the axon around the cell body before splitting in a T form. 8. Cells are surrounded by large 8. Few satellite cells in number of satellite cells in a discontinuous layer (interruptedby continuous layer the dendrites) NEUROGLIA Glial cells are 10 times more abundant in the mammalian brain than neurons.They surround the cell bodies and processes. Central neuroglia: include Astrocytes, Oligodendrocytes, Microglia and Ependymal cells. Peripheral neuroglia: include Schwann cells and Satellite cells. Astrocytes (Macroglia) Oligodendrocytes Microglia (Mesoglia) Origin Ectodermal Ectodermal Mesodermal Site Grey matter and white matter Shape Large star shaped cells with Medium sized cells - Smallest cells with multiple processes which have few many branches. processes. - The cell body and the branches are decorated by spines. Nucleus Large pale Medium dark Small dark Cytoplasm Intermediate filaments highly dense Many lysosomes (GFAP) Centrioles Present so can divide and form tumors Absent Page | 8 Subtypes 1- Cytoplasmic astrocytes: 1- Satellite cells: ▪ In grey matter ▪ In grey matter. ▪ Granular cytoplasm ▪ closely associated ▪ Many short processes with the cell body 2- Fibrous astrocytes of neurons. ▪ In white matter 2- Interfascicular ▪ Fibrous cytoplasm ▪ In white matter ▪ Many long processes ▪ Between bundles of axons. Function 1. They have processes with 1- Support nerve Phagocytic cells so expanded end feet linked to cells. can be stained by endothelium of blood 2- Formation of trypan blue. capillaries so can control Myelin sheath. metabolic exchanges 3- Electric insulation. between nerve cell and blood. 2. Blood brain barrier. 3. Structural support. 4. Repair process by formation of scar tissue. Peripheral neuroglia a- Ependymal cells Line central canal of spinal cord and ventricles of brain. They form simple cuboidal or columnar epithelium that may beciliated in places. Cilia may be involved in propulsion of CSF. Ectodermal in origin. b- Schwann cells In peripheral nervous system. Responsible for myelin production, electric insulation and regeneration. Ectodermal in origin. c- Satellite cells Low cuboidal cells In peripheral nervous system. Around nerve cells in ganglia Synapse - Site of functional contact between neurons or neurons and other effector cells (as muscle & gland cell). Its main function is to transmit impulse from the presynaptic cell to postsynaptic cell. ❖Classification: a) According to method of transmission of nerve impulse: 1. Chemical: most common, in which conduction of impulses takes place by release of neurotransmitters. Page | 9  2. Electrical: contain gap junctions that allow movement of ions between cells and so permit the spread of electric current. They have been demonstrated in cerebellum. b) According to the site of contact of the axon: 1- Axosomatic: axon forms synapse with cell body. ▪ Most excitable because: a- large number of Na+ channels b-Lower threshold (11 mv depolarization) ▪ Least numerous 2- Axodendritic: axon forms synapse with a dendrite. 3- Axoaxonic: axon forms synapse with an axon ▪ Least excitable (15 mv depolarization). ▪ Most numerous ❖By electron microscope: Synaptic knobs: o Has protein on its membrane called t-snare o It contains Vesicles: Contain protein called v-snare - Types : 1. Clear vesicles: Containing rapidly acting transmitter e.g. Acetyl choline 2. Granular vesicles: Containing slowly acting chemical transmitter o It contains also Mitochondria Synaptic cleft: - 30- 50nm width - It contains extracellular fluid (ECF): Na+, Cl- Post-synaptic membrane: Contain receptors formed of: o Binding protein (to unite with the transmitter). o Ligand channels: )1 Na+ channels: Allow Na+ entry (influx) (2 Cl- channels: Allow Cl- entry (influx (3 K+ channels: Allows K+ exit (efflux) Synaptic transmission It is Chemical transmission Is transmission of impulse (action potential) from one neuron to another It is chemical by release of chemical Transmitter. ❖Mechanism Synaptic Transmission: 1- Release of Chemical Transmitter: - The action potential in the presynaptic nerve reaches the terminal knob - Opens the voltage gated Ca++ channels present on membrane thickening called active zone. - Ca++ enters the knob according to concentration & electric gradient - The vesicles move to the active zone - v-snare fuses with t- snare leading to rupture of vesicles - Release of chemical transmitter in synaptic cleft - The amount of transmitter released is directly proportionate to amount of Ca++ entered 2- Union of chemical transmitter with its receptors 3- Synaptic potential: Changes in ion fluxes through membrane lead to change in resting membrane potential (RMP) of postsynaptic membrane to become: a. Less negative: Causing Excitatory Postsynaptic Potential (EPSP) b. More negative: Causing Inhibitory Postsynaptic Potential (IPSP) Page | 10  4- Removal of neurotransmitters and termination of response :By one of the following a. Inactivation of transmitter→By specific enzymes at post synaptic membrane b. Passive diffusion away from synaptic cleft c. Active re-uptake of transmitter by axon terminal to be stored or destroyed) d. Removal by glial cell Synaptic Potentials 1) Presynaptic Potentials (PSP) : - Types: A- Pre-synaptic inhibition By 3rd inhibitory neuron: Its axon terminal anastomoses with the axon terminal of an excitatory presynaptic neuron (before it reaches the synapse) Releases an inhibitory chemical transmitter which either: 1. Closes voltage gated Ca++ or 2. Closes Na+ channel or 3. Opens K+ or Cl- channels The end result is reduced Ca++ entry to synaptic knob which in turn decrease release of chemical transmitter. B- Pre-synaptic facilitation: Sensitization By 3rd excitatory neuron: - Secretes excitatory chemical transmitter (serotonin) - Serotonin increase cAMP in pre-synaptic terminals → activate kinase which phosphorylate K+ channels → closure of K+ channels → prevent repolarization & prolong the action potential. - The action potential → opens Ca++ channels → increase Ca entrance → increase release of chemical transmitter (may continue for 3 weeks). - It is the base of sensitization involved in learning & memory. C- Postsynaptic Potentials (PSP) : Types: 1- Excitatory Post-Synaptic Potential [EPSP] 2- Inhibitory Post-Synaptic Potential [IPSP] 3- Grand Post-Synaptic Potential [GPSP] 1-Excitatory Post-Synaptic Potential 2-Inhibitory Post-Synaptic Potential [IPSP] [EPSP] 1.Post-synaptic membrane is in a state of: Local partial depolarization Local partial hyperpolarization (excitatory state) (inhibitory state) 2.Produced by: Combination of excitatory chemical Combination of inhibitory chemical transmitter transmitter (e.g. acetyl choline) with its (e.g. GABA) with its specific receptor. specific receptor 3.Occurs after: 0.msec from pre-synaptic nerve stimulation 5msec from pre-synaptic nerve stimulation 4.Reaches max after: 1.5 msec 1.5msec 5.Lasts for: 5 msec 3msec Page | 11  6.During this period: The membrane is facilitate (ie needs weaker The membrane is inhibited (ie needs higher stimulus to be excited) "high excitability" stimulus to be excited) "low excitability" because the potential is away from firing level 7.It is caused by: 1. Opening of ligand gated Na+ 1. Opening of ligand gated Cl - channels which allow: Na+ entry 2. Opening of ligand gated K+ channels (according to concentration& 3. Closure of ligand gated Na+ electric gradients) 4. Closure of ligand gated Ca++ channels 2. Opening of ligand gated Ca++ channels. 8.It can be summated To reach the threshold value, it must be summated Summation could be: Summation could be: Temporal (time) Spatial (space) Temporal (time) Spatial (space) One pre- synaptic Several pre- knob is stimulated synaptic knobs are repetitively stimulated simultaneously)40( When excitation reaches firing level, action potential starts. Up to 50 EPSPs have to summate to reach the threshold value Excitatory postsynaptic potentials, showing that simultaneous firing of only a few synapses will not cause sufficient summated potential to elicit an action potential, but that simultaneous firing of many synapses will raise the summated potential to threshold for excitation and cause a superimposed action potential 3-Grand Post-Synaptic Potential [GPSP] It is the sum of all EPSPs and IPSPs occurring at the same time in one post synaptic neuron. If EPSP equal to IPSP input: GPSP is zero If EPSP is slightly greater than IPSP input: GPSP will be depolarization but do not reach firing level If EPSP is much greater than IPSP input: GPSP is depolarization reach firing level If IPSP is greater than EPSP: GPSP is hyperpolarization Page | 12  Post-synaptic Potential Action Potential 1. Not obey all or law 1. Obey all or non law 2. Graded 2. Can not be graded 3. No absolute refractory period 3. there Is absolute refractory period 4. Summated 4. Can not be summated 5. Not propagated 5. Propagated 6. 20msec 6. 1msec 7. Make the membrane more or less negative 7. Always make the membrane less negative Three states of a neuron. A. Resting neuron, with a normal intraneuronal potential of (-65 millivolts). B. Neuron in an excited state, with a less negative intraneuronal potential (-45 millivolts) caused by sodium influx. C. Neuron in an inhibited state, with a more negative intraneuronal membrane potential (-70 millivolts) caused by potassium ion efflux, chloride ion influx, or both. Characters of synaptic transmission 1. Forward direction→Impulses are conducted from pre-synaptic to post-synaptic neuron (as neurotransmitter is released from pre- synaptic neuron) 2. Synaptic delay: - Is the time taken by an impulse to be conducted through synapse - It equals 0.5 msec “Millisecond ” - It is taken by: 1-Release of chemical transmitter 2 - Union with receptors 3-Opening ionic gates 4-Building post-synaptic potential 3- Central delay→Time of conduction of impulse along the synapses →Equals: Number of synapses in reflex arc multiplied by 0.5 msec 4-Fatigue→It is decreasing rate of discharge of impulse from post-synaptic neuron after long period of high frequency stimulation of pre-synaptic neuron - Cause: a) Exhausted pre-synaptic vesicles b) Inactivated post-synaptic receptors Page | 13  - Benefit: Stops CNS over excitation, as in epileptic fits where fatigue stops convulsions 5- Synaptic Plasticity→Change in functions according to demand placed on synapse. So, synaptic transmission can be strengthened or weakened for short or long duration Factors affecting synaptic transmission 1. Changes in composition of internal environment: a- PH of blood: 1) Alkalosis→ Increases excitability →increases synaptic transmission → convulsions eg Hyperventilation - Mechanism: In alkalosis, protein carry more negative charge → combine with ionized Ca → decrease ionized Ca → open Na+ channels → depolarization 2) Acidosis→ Decreases excitability → decreases synaptic transmission → coma eg diabetes → acids (as β-hydroxy butyric acid) b- Hypoxia: -Decrease synaptic transmission - Because decrease O2 supply→ Pyruvate & lactic acids accumulate - Interrupted cerebral circulation for 3-5 sec→ unconsciousness c- Hypoglycemia: - Decrease synaptic transmission - Because glucose is the only fuel for brain for energy production - Energy is needed for formation of transmitter & active re-uptak d- Hypocalcemia: Low Ca++ facilitate synaptic transmission As it increases the excitability of postsynaptic membrane e- Hormones: -May inhibit or facilitate synaptic transmission - e.g. thyroid hormones facilitate synaptic transmission 2. Drugs: a. Theophylline & caffeine→Facilitate synaptic transmission (as they lower the threshold of excitability & depolarize post-synaptic membrane) b. Hypnotics, Analgesics & Anaesthetics→ Decrease synaptic transmission by: i. Stabilizing cell membrane → hyperpolarization Or ii. Interfere with transmitter synthesis c. Strychnine→ Competes with glycine (Inhibitory chemical transmitter) leaving excitatory pathway unaffected→ convulsions & spasm. 3. Diseases: I. Parkinsonism→ A disease of basal ganglia - Causing decrease release of Dopamine (inhibitory chemical transmitter) leaving acetyl choline (excitatory chemical transmitter) → Hypertonia (rigidity) II. Tetanus→Decrease release of GABA (inhibitory chemical transmitter) leaving excitatory chemical transmitter → spastic paralysis muscle spasm → locked jaw & asphyxia III. Myasthenia Gravis “MG”→ Autoimmune disease: Antibody against acetyl choline receptors in neuromuscular junction → severe muscle weakness. Page | 14 IV. Botulism toxin→ Block the release of acetylcholine (excitatory chemical transmitter) at neuromuscular junction leading to flaccid paralysis. Clinical Application - Improperly prepared salted fish may contain Botulinum toxin causing botulism, which may end in respiratory failure - We inject Botulinum toxin (Botox) into muscle for therapeutic purposes as: - a-Anti-wrinkle treatment (Cosmetology) b-Achalasia of the cardia c-Anal fissure Organization of Neurons in Neuronal Pool ❖Definition: Neuronal pool is a collection of neurons having the same function in CNS ❖Similarities of organization: 1- Divergence: Def.: One neuron stimulates many neurons Function: 1-Amplification: e.g. one pyramidal cell in motor cortex stimulates 100- 1000 AHCs in spinal cord 2- Distribution of signals: e.g. painful stimulus stimulate AHCs of muscles on same & opposite side (flexor withdrawal reflex) "Divergence" in neuronal pathways. A. Divergence within a pathway to cause "amplification" of the signal. B. Divergence into multiple tracts to transmit the signal to separate areas. Page | 15  2- Convergence: Def.: Many neurons stimulate one neuron Function: 1-Intensification of stimulus due to spatial summation - Interpretation of information carried from different sites & received by one neuron "Convergence" of multiple input fibers onto a single neuron. A. Multiple input fibers from a single source. B. Input fibers from multiple separate sources 3- Excitation Field: - Def.: It is number of neurons with which one afferent neuron synapse Central neurons in excitation field Peripheral neurons in excitation field - Discharge zone - Facilitation zone (subliminal - When afferent neuron is fringe) stimulated, these cells are - Which cannot reach threshold stimulated & reach threshold value and so, they are only facilitated value and discharge - The stronger the stimulus → the - If overlap occurs in the wider the discharge zone center - The weak the stimulus → the small excitation field formed mainly of subliminal fringe - Overlap between excitation field may lead to: 4- Occlusion 5- Facilitation Due to: Decrease the number of discharge Due to: Increase the number of discharge zone zone are Discharge" and "facilitated" zones of a neuronal pool. Page | 16  6- Inhibitory Circuits: a. Lateral inhibition: A central neuron is stimulated while the neurons at the periphery are inhibited by one excitatory input through inhibitory interneuron Importance: Sharpen the sensation b. Negative feedback inhibition: Input fiber stimulate output fiber which in turn inhibit the input by inhibitory inter neuron c. Reciprocal innervation: It is stimulation of one muscle and inhibition of its antagonist by excitation of one nerve. This is carried through inhibitory interneuron Inhibitory circuit. Neuron 2 is an inhibitory neuron 7- Activating Circuits: “After discharge” Def.: The output continues to discharge after stoppage of stimulation of the input Mechanism: a- Parallel circuits: -The input is connected to the output by many parallel circuits, each contains different number of synapses - This leads to arrival of successive impulses to output neuron to prolong the discharge b. Reverberating circuits “Oscillatory circuits” (closed circuits): - The output neuron sends collateral to restimulate itself. - It can be stopped by fatigue of the synapses or inhibitory impulses from outside. Skin ❖Structure: 1- Epidermis: - Outer epithelial layer (keratinized stratified squamous epithelium). - Derived from ectoderm. 2- Dermis: - Thicker deep CT layer. - Derived from mesoderm. N.B. Hypodermis: is not a part of the skin (Greek; hypo = under, dermis = skin). ❖Types of skin According to thickness of epidermis, skin is classified into thick and thin Thick (Non-Hairy) Skin It has a thick epidermis (400-1400 µm) and a thick horny layer Present in palms and soles. It is formed of epidermis and dermis. Page | 17  The Epidermis It is a keratinized stratified squamous epithelium. Thicker over soles than palms. Avascular layer receiving its nutrition by diffusion. Rich in free nerve endings. The epidermis is formed of keratinocytes and non-keratinocytes. a- Keratinocytes 85% of the cells in epidermis. Deeper layers are continuously dividing, differentiating, and accumulating keratin filaments (keratin formation) while progressing upwards. Superficial layers are continuously shed off. According to keratinocytes maturation, epidermis consists of 5 layers: Diagram showing layers of skin - Stratum Basale or (Basal Cell Layer): LM: Single layer of low columnar or cuboidal cells, resting on a clear wavy basement membrane. Basophilic cytoplasm with large basal oval nucleus. Intense mitotic figures (responsible for renewal). Melanocytes and Merkel’s cells are found in this layer EM: Attached to each other and to the following layer by desmosomes and to basement membrane by hemi-desmosomes. Rich in free ribosomes and polysomes with few other organelles (G.A, mitochondria and rER). Keratin intermediate filaments ending in desmosomes. Page | 18  - Stratum Spinosum (Prickle Cell Layer): LM: 4-8 layers of polyhedral cells are present above the basal cell layer. Less basophilic cytoplasm than cells of stratum Basale. Cells have central rounded nuclei. Borders of cells appear to be separated from one another by small spaces that are traversed by fine spine-like processes (desmosomes), giving prickly appearance. Langerhans cells are present in this layer. ❖ Malpighian layer: Consists of both stratum Basale and stratum spinosum. EM: bundles of intermediate filaments (Tono-filaments) that end into the dense plaques of numerous desmosomes along highly inter- digitating cell boundaries. - Stratum Granulosum (Granular Cell Layer): LM: layers of spindle-shaped cells above the spinous cell layer. Deep basophilic and granular cytoplasm with flat pale nuclei. EM: The cytoplasm shows 2 types of granules. A. Keratohyalin granules: - Non membranous. - Aggregate to form keratin filaments (tonofilaments) B. Membrane-coated lamellar granules: - Membranous granules. - Release a lipid-rich secretion that fills spaces between cells. 4- Stratum Lucidum (Clear Layer): LM: Thin, lightly stained, clear, homogeneous layer. Formed of much flattened cells. Nuclei are on their way to disappear by karyolysis. EM: Thickened cell membranes. Few remnants of desmosomes. Organelles disappear (by lysosomal activity). Nuclei appear as ghosts or completely absent Densely packed keratin filaments (Tono- fibrils) embedded in an electron-dense matrix formed by keratohyalin granules. 5- Stratum Corneum (Horny Layer): LM: Thick eosinophilic layers formed of heavily keratinized dead cells, called scales. EM: Thickened cell membranes attached together by remnants of desmosomes. Filled with mature keratin filaments (Tono-fibrils) embedded in amorphous matrix. No nuclei nor organelles. Page | 19  Non-Keratinocytes 1- Langerhans Cells: Origin: Bone marrow precursors migrate via blood to the dermis then epidermis. LM: ▪ Represent 3-8% of epidermal cells. ▪ They are stellate-shaped cells found mainly between cells of the stratum spinosum of epidermis. ▪ In H.&E. skin sections; cell appears with a dark-staining nucleus and a pale clear cytoplasm. ▪ They can be identified using vital stains. EM: ▪ A prominent Golgi complex and numerous lysosomes ▪ Special tennis-racquet-shaped granules (Birbeck’s granules). Some may contain hydrolytic enzymes. ▪ The nucleus is dark and highly irregular. ▪ Absence of keratin filaments and desmosomes. ▪ Absence of melanin granules. ▪ Absence of cell junctions between them and keratinocytes. Function: Acts as antigen presenting cell; capable of binding antigen that contacts skin and then presenting it to T-lymphocytes. So, they have a significant role in skin immunological reactions (allergic dermatitis). 2- Merkel’s Cells: Origin: Ectodermal in origin. They are modified epithelial cells. LM: ▪ They resemble epidermal cells. ▪ Present in-between cells of the basal layer. Abundant in highly sensitive skin like that of fingertips and at the bases of some hair follicles. ▪ Free nerve fiber (sensory) traverses basal lamina to terminate as disc-shaped expansions beneath Merkel’s cell forming Merkel cell-neurite complex. EM: ▪ Cells are attached to neighboring keratinocytes by desmosomes. ▪ Cytoplasm contains electron-dense granules resembling those of neuroendocrine cells elsewhere (APUD). ▪ Deeply invaginated nucleus. Function: - Mechanoreceptors for light touch sensation. - Neurosecretory function (granules). 3- Melanocytes: Origin: Precursors arise from neural crest (ectoderm) and migrate to the skin early in development and differentiate to melanocytes. LM: ▪ Cell bodies of melanocytes are present in-between and just below the cells of stratum Basale. ▪ They have rounded cell bodies from which long irregular cytoplasmic processes extend between keratinocytes. Tips of these extensions terminate in invaginations of the cells present in stratum Basale and stratum spinosum. Page | 20  ▪ Cells have rounded pale-stained nuclei. ▪ The H.&E-stained skin sections do not demonstrate melanocytes EM: ▪ Cell shows all characters of active protein synthesizing cells: abundant rough endoplasmic reticulum, prominent Golgi apparatus and mitochondria. ▪ Granules are known as melanosomes. ▪ Nucleus shows euchromatin and a prominent nucleolus. ▪ No desmosomes between melanocytes and keratinocytes. ▪ Hemidesmosomes are present to bind melanocytes to basal lamina. Function of melanocytes: ▪ Melanin pigment is formed by the epidermal melanocytes (as they can synthesize tyrosinase enzyme which is essential for melanin synthesis). ▪ Ultraviolet light speeds melanin synthesis. The Dermis o Connective tissue under epidermis. - Thicker than epidermis. o Irregular surface having projections (dermal papillae) which fit into concavities in the epidermis (epidermal ridges). o Formed of 2 layers: Papillary layer and Reticular layer 1. Papillary layer 2. Reticular layer Thinner superficial layer Thicker deep layer Forms dermal papillae. Formed of loose C.T. Formed of dense C.T. More cellular (fibrocyte, lymphocyte, Less cellular (fibrocyte, macrophage, macrophage, mast cell, adipocyte). lymphocyte, mast cell, adipocyte). Fine C.T. fibers (type III collagen & elastic fibers). C.T. fibers type I (bundles) & elastic fibers. More vascular (to nourish epidermis) Less vascular Receptors: Meissner’s corpuscles. Receptors: Pacinian corpuscles, Ruffini’s end organ & Krause’s end bulb Dermal-epidermal junction: - Zigzag-like interdigitations between dermal papillae and epidermal ridges forming the fingerprints which are of medico legal importance. - Its importance: ▪ Provide attachment of epidermis to dermis. ▪ Surface area for nutrition of epidermis. ❖ Factors fixing epidermis to dermis: 1- The basement membrane of epidermis. 2- Hemidesmosomes: between basal epidermal cells & basement membrane. 3- Dermal papillae interdigitating with epidermal ridges Page | 21  Thin (Hairy) Skin It covers all the body except palms, soles, tips and sides of fingers and toes. Eyelid has got the thinnest skin in the body. Thin skin has the basic skin structure as thick skin but with some differences. Differences between thick and thin skin. Thick skin Thin skin Palms & soles Sites Tips, sides fingers & toes Rest of the body Epidermis: Thicker Thinner 1- Malpighian layer Thicker Thinner 2- Granular layer Thicker (3-5) Thinner(single) 3- Clear layer Present Less apparent 4- Horny layer Very thick Very thin Dermal papillae More, large, regular Fewer, small, irregular Appendages: Absent Present Hair follicles Sebaceous glands Absent Present Arrector pili muscles Sweat glands More numerous Less numerous Sweat gland Type: Simple tubular coiled glands. Site: Deep in the dermis, all over the body except: glans penis & nail beds. Eccrine sweat glands Apocrine sweat glands Site All over the body except glans penis Thin skin of axillary, pubic & nail beds & perineal regions More numerous Less numerous More in thick skin Not present in thick skin Mode of Merocrine (by exocytosis) secretion Small & Narrow lumen Large in size & Wide lumen Formed of three types of cells: Formed of two types 1. Large (Clear) cells: of cells: ▪ More numerous 1. Simple cubical cells: ▪ Broad base, narrow apex. ▪ Eosinophilic cytoplasm ▪ Pale cytoplasm (glycogen). ▪ The apical cytoplasm ▪ Intercellular canaliculi contains numerous small between clear cells. granules that discharge Secretory part 2. Small (dark) cells: their content by Page | 22  ▪ Less numerous exocytosis. ▪ Narrow base, wide apex 2.Myoepithelial cells ▪ Dark cytoplasm (dark granules containing glycoprotein). N.B.: Watery secretion of clear cells passes through canaliculi to lumen where it mixes with protein product of dark cells. 3. Myoepithelial cells Spiral course in dermis& epidermis Spiral course in dermis Opens into epidermis Opens into a hair follicle Lined by 2 layers of cubical cells Lined by 2 layers of cubical Excretory duct Appears darker than secretory part cells Sweat is a clear watery fluid (water, Start function at puberty. NaCl, urea & ammonia) with low They secrete viscous protein content. odorless secretion that Function becomes offensive by Its main function is body temperature bacterial action. regulation. Sebaceous Glands Development: develop as outgrowths of the external sheath of the hair follicle. Type: Simple alveolar (acinar) or branched alveolar exocrine gland. Sites: In the dermis of thin skin: - Usually associated with hairs. - Rarely without hairs: eyelids. Structure: a) Secretory part: each alveolus is lined by: Basal flattened germinal cells: large polyhedral cells are produced by mitosis of these basal cells. Large polyhedral vacuolated cells: The cells gradually become filled with lipids. b) Excretory duct: Short & wide and opens in upper 1/3 of hair follicle. Lined by stratified squamous epithelium continuous with hair follicle. ❖ Mode of secretion: by holocrine secretion The cell undergoes programmed cell death (apoptosis) and both the secretory product and cell debris are discharged from the gland through their short ducts. N.B. : Hypodermis: is not a part of the skin (Greek; hypo = under, dermis = skin). Nerve Endings A. Receptors: Receive external or internal stimuli and convert them to nerve impulses: Exteroceptors: receive external stimuli. Proprioceptors: receive stimuli from the muscle. Interceptors: receive internal stimuli. B. Effectors that bring efferent nerve impulses to effectors (muscle or gland). Page | 23  Nerve Endings in Epithelium A-Receptors are exteroceptors a) Free nerve endings: In epidermis of skin and cornea of eye. They are mechanoreceptors for pain, temperature and touch Nonencapsulated. Myelinated nerve loses its myelin below the basement membrane and passes in between the epithelial cells. b) Merkel endings: Epidermis of hairless skin. Mechanoreceptors for touch. Nonencapsulated. The nerve loses its myelin sheath and forms a disc like expansion under Merkel cell near the base of the epidermis. c) Peritracheal nerve endings: Present in hairy skin around hair follicle Mechanoreceptors for touch and movement of hair. Nonencapsulated. d) Neuroepithelium endings: Taste buds in tongue for taste. Organ of Corti in ear for hearing. Macula utriculi, macula sacculi and cristae ampullaris for equilibrium. B) Effectors: These are autonomic nerve endings supplying glandular epithelium as lacrimal and salivary glands. The unmyelinated nerve fibers form networks just outside the basal lamina of the epithelium. From there, branches penetrate the lamina and end between the bases of the glandular cells. Nerve Endings in Connective Tissue - All are receptors; 1- Free nerve endings: Similar to those in epithelium. Present in dermis of skin and stroma of cornea. 2- Meissner's corpuscle: Dermal papillae of skin especially in palm of hands and sole of feet. It is a mechanoreceptor for touch. Encapsulated, oval in shape. Axon loses its myelin to enter the corpuscle and spirals up between modified flattened Schwann cells, arranged transversely until it ends at upper pole of corpuscle. 2- Krause's end bulb: Deep in dermis It is a mechanoreceptor for touch. Page | 24  Encapsulated, ovoid bodies. Axon enters the corpuscle after losing its myelin and branches repeatedly inside. 3- Ruffini corpuscles: Deep in dermis of skin especially in sole. It is a mechanoreceptor for stretching and twisting of skin. Encapsulated, fusiform bodies. The axon enters the capsule after losing myelin sheath and branches between parallel collagen fibers inside. 4- Pacinian corpuscle: Dermis & hypodermis of skin, periosteum of bone, joint capsule and C.T. of some organs as pancreas, wall of the rectum & urinary bladder. It is a mechanoreceptor for vibration and pressure that responds to displacement of the capsule lamellae. The Pacinian corpuscle in joint capsule is one of the proprioceptors. Encapsulated large ovoid up to 1mm in length It has a thin C.T. capsule enclosing 20-60 concentric lamellae consisting of very thin flat cells (probably modified Schwann cells) separated by narrow spaces filled with gel like material. Towards the center, the lamellae become closely packed. Myelinated nerve fiber enters the corpuscle at one pole. Its Schwann cell sheath becomes continuous with the capsule while myelin sheath ends inside the corpuscle. Naked nerve fiber runs parallel to the longitudinal axis and ends in a small expansion. Nerve Endings in Muscular Tissue A- Receptors: Muscle spindles: Site: in skeletal muscles. More numerous in muscle involved in fine movements as intrinsic muscle of hand and in antigravity muscles. It is a mechanoreceptor for stretch-muscle length. It is one of the Proprioceptors within is responsible for regulation of the muscle tone through stretch reflex. It also keeps the CNS informed about the length of the muscle thereby indirectly influencing the control of voluntary muscle. Shape: fusiform. They lie parallel to muscle fibers. Size: up to 6 mm long but less than 1 mm in diameter. Structure: Capsule surrounding lymph filled space that contains intrafusal muscle fibers and nerve fibers. - Intrafusal fibers: much smaller than skeletal muscle fibers and they have central non striated area containing the nuclei. They are of 2 types: Page | 25  o Nuclear bag type: the central nuclear area is dilated. o Nuclear chain type: no dilatation and the nuclei are in the form of chain. - Afferent nerves: unmyelinated sensory nerve fibers that envelope the intrafusal muscle fibers. Effectors: Motor end plate (Neuromuscular junction) Sensory Receptors Definition: They are modified nerve endings of afferent fibers which receive (detect) different stimuli & convert (transform) them into action potentials Functions: - Detectors: Detect changes in the surrounding environment -Transducers: Transform any form of energy in the stimulus into action potentials Classification: According to 1. Its site: - Superficial “Cutaneous” -Deep -Visceral -Special sense 2. Physiological: i. Mechanoreceptors: Detect mechanical deformity in the receptors as: Touch - Pressure - Sound (cochlear receptors) Acceleration (vestibular receptors) Blood pressure (baroreceptors) They are found in: -Skin -Mucous membrane -Muscle -Tendons -Joints (Proprioceptors) - Blood vessels -Lungs -Inner ear ii. Thermoreceptors: - In hypothalamus for body temperature regulation - In skin, mucous membrane: Detect cold & warm energy B. Chemoreceptors: - Taste - Smell - Osmoreceptors - Glucoreceptors - CO2 - O2 - H+ C. Nociceptors: Detect pain D. Electromagnetic: Detect light Properties: 1. Specificity: (Muller's law): Each receptor is sensitive to one type of sensation called adequate stimulus eg light for photo receptors Other forms of energy can stimulate the receptor, but it needs stronger stimulus than the adequate one 2. Excitability: Generator potential “Receptor potential” [RP]: Def.: It is a state of partial depolarization in the receptor membrane which occurs when the receptor is stimulated Receptor potential spreads passively with decreasing its magnitude to : Adjacent part of sensory nerve (unmyelinated) or 1st node of Ranvier (myelinated nerves) If depolarization reaches the firing level → it leads to action potential which is propagated by salutatory conduction As long as there is receptor potential with enough magnitude to generate action potential → there is train of nerve impulses Page | 26  Ionic basis of RP: The energy of the stimulus causes nonspecific opening of Na+ channels → Na+ entry leading to partial depolarization Number of opened channels: Is directly proportional to intensity of stimulus. In some receptors (as photoreceptors) → the electromagnetic waves cause closure of Na+ channels → hyperpolarization NB: Receptor potential is studied in Pacinian corpuscle (mechanoreceptor): It is stimulated by mechanical pressure which leads to deformity & generates receptor potential Receptor Potential Action Potential 1. A local state of partial depolarization 1. It is complete depolarization which spreads passively followed by overshoot, reversal of 2. Due to non-specific increase in polarity permeability to Na+ 2. It Is due to increase in Na+ & K+ 3. Not obey all or non-law. permeability. - It has a variable magnitude. 3. Obey all or non-law. 4. Can be graded & its amplitude is - It has a fixed magnitude. increased by increasing intensity of 4. Can not graded stimulus. 5. Followed by absolute refractory 5. No absolute refractory period period 6. Can be summated 6. Can not be summated 7. Its duration is 5- 10 msec (longer than 7. Its duration of spike: 2 msec AP) → allow repetition of AP 8. Blocked by local anesthesia 8. Not blocked by local anesthesia 3. Adaptation of receptors: - Definition: Adaptation is decline in the receptor potentia1 and frequency of impulses inspite of constant maintained application of the stimulus - Classification: According to rate of adaptation, receptors are classified into: Rapidly adapting receptors (phasic) eg touch receptors - They adapt rapidly to continuously applied stimuli but respond rapidly if change take place Moderately adapting receptors As: Temperature, Smell & Taste Slowly adapting receptors (tonic) eg:- Pain receptors - Muscle spindle - Alveolar stretch receptors - Pain receptors are slowly adapting or they do not adapt at all - Their function is: To keep the brain continuously informed about dangerous changes in environment. - Mechanism: Each receptor has its own property of adaptation ▪ eg: 1- Rods & cones: Adapt by changing the concentration of their pigment 2- Mechanoreceptors: Adapt by: 1. Remodeling (readjustment) of the receptor structure: Where maintained pressure → steady displacement in outer lamellae but inner lamellae of nerve fiber slip back to original. Position ending distortion → decline in generator potential 2. Inactivation of Na+ channels in terminal nerve fiber 3. Inactivation of Na+ channels in 1st node of Ranvier. Page | 27  Sensory Code - Definition: It is the ability of CNS to recognize type “Modality”, site “Locality” & strength “Intensity” of sensation i. Code For Type of Sensation: Each receptor is most sensitive & specialized to one type of stimuli The sensation perceived to brain will be the same whatever the method of stimulation This known as MULLER LAW. ii. Code For Site of Sensation: Each part of body send sensory signal to particular area of the brain & the brain project the sensation to the same part of the body This known as LAW OF PROJECTION iii. Code For Strength of Sensation: Brain depends on frequency of action potential to determine the strength of sensation Increase frequency mean increase in strength Somatic Sensations - Definition: Feeling produced by application of stimulus - Classification: Classified into: General Sensations: - Somatic sensations - Organic Sensation (Thirst, hunger, sexual desire) Special sensation: - Hearing - Vision - Taste - Smell - Emotional: As fear Somatic sensations Mechanoceptive Sensation a- Tactile sensation: 1- Touch: Types: 1- Crude touch: Receptors: Free nerve ending& Hair end organs Afferent: Aδ fibers Pathway: Ventral spino-thalamic tract Poorly localized e.g. feeling of clothes & hair comb Tested by: A piece of cotton passed on skin while eyes are closed 2- Fine touch: Receptors: Merkel’s & Meisner's Afferent: Aβ fibers Pathway: Dorsal column - Well localized a- Tactile localization: It is the ability to localize the point touched while eyes are closed b- Tactile discrimination: It is the ability to feel two points touched simultaneously as two separate points while eyes are closed The distance between the two touched points should be above the threshold distance. Threshold distance is shorter if: A. Number of receptors is: More B. Number of afferent fibers is: More C.Area of cortical representation is: Greater D.Central convergence of afferent is: Less c- Texture of materials: It is the ability to know the texture of materials eg silk or wool by touching them while eyes are closed 2- Tickling & itching: - Receptors: Free nerve endings Page | 28  Afferent: C fibers (different from pain fibers) Pathway: Ventral spino-thalamic tract Tickling is ability to feel light moving things on the skin as insects which cause local repeated mechanical stimulation Itching is the sensation caused by chemical substance secreted near the receptors as histamine, Kinins & proteolytic enzymes 3- Stereognosis: - Receptors: Mixture of receptors of different sensations Afferent: Aβ fibers - Pathway: Dorsal column It is the ability to recognize the nature of familiar objects put in hand with both eyes closed It depends on:- All cutaneous & deep sensation - Previous knowledge about the object 4- Pressure: - Receptors: Pacinian corpuscle - Afferent: - Crude: Aδ fibers Fine: Aβ fibers - Pathway: Dorsal column - It enables the person to know the weights of objects & discriminates between different weights 5- Vibration: - Receptors: -Meissner's corpuscle: Responds to vibration up to 80 cycles/sec - Pacinian corpuscle: Responds to vibration up to 500 cycles/sec - These receptors contribute to sense of roughness when hand is passed over rough Afferent: Aβ fibers Pathway: Dorsal column o Vibration is rhythmic repetitive pressure sensation o It is felt when tuning fork put on bony prominences (as leg malleoli) to allow magnification of stimulus and avoid its damping by soft tissues o Impaired vibration sense: is an early diagnostic sign in degeneration of posterior column of spinal cord o e.g. : 1- Uncontrolled Diabetes mellitus “DM ” 2- Pernicious anemia “PA” b- Kinesthetic sensation: Proprioceptive sensation: Receptors: Types: -Rapidly adapting: Pacinian corpuscle (for rate of movement) - Slowly adapting: Muscle spindle & Golgi organ Sites: A) In: - Small joints as fingers - Large joints as knee B) In ligaments & tendons Pathway: Dorsal column They inform the CNS about: 1- Static: Sense of position of different parts of body 2- Kinetic (dynamic): Sense of movements & Rate of movements of different parts of body NB: - Joints→ For each degree of angulations, there is specific receptors in joints which discharge to specific area in cortex. In thalamus, there is specific neuron for slow rate of movement and other for high rate of movement Page | 29  Proprioceptive impulses go to: o Cerebellum: Via spino-cerebellar tract to keep equilibrium o Cerebral cortex: Via dorsal & ventro-lateral tract. Thermal Sensation Definition: Sense of: - Warm -Cold Thermoreceptors : Types: Cold receptors: Free nerve ending attached to: C & Aδ fibers Warm receptors: Free nerve endings attached to: C fibers Two subtypes of pain receptors (high threshold receptors): - Cold pain receptors: For freezing cold - Heat pain receptors: For burning hot sensation Characters: - Are located immediately under the skin o Number: Cold receptors: Are more numerous than warm receptors o Distribution: Greatest in: Lips Moderate in: Fingers tips Least in: Trunk o Mechanism of stimulation: Stimulated chemically by: ✓ Accumulated metabolites due to change in metabolic rate ✓ Each 10° Change increase the concentration of metabolites two folds o Adaptation: Warm receptors→ Adapt more rapidly than cold receptors (but both are moderately adapting receptors) Discharge frequencies at different skin temperatures of a cold-pain fiber, a cold fiber, a warmth fiber, and a heat-pain fiber Detection of thermal sensation: - According to range of temperature they detect: o Cold receptors: - Stimulated from 10-43° - Maximum rate of discharge at 25°C o Warm receptors: - Stimulated from 30-50°C -Maximum rate of discharge at 45°C o Cold pain receptors: - Stimulated from 5-10°C - Maximum rate of discharge at 5°C o Warm pain receptors: Stimulated above 45°C NB: - At 0°C : Degree Centigrade “Celsius” there is no action potentials ie anesthesia - At 35°C: - Comfort zone exist where awareness of temperature disappears - Due to equal discharge of warm & cold receptors Temperature sensation perceived depends on: The original skin temperature The rate of temperature change The surface of the skin exposed to temperature change Page | 30 THIS PAGE INTENTIONALLY LEFT BLANK Page | 31  Ophthalmic nerve Maxillary nerve TRIGEMINAL NERVE Page | 32  Cranial nerves ❖ It is attached to pons. ❖ It contains sensory & motor fibers. ❖ It divides into 3 branches (ophthalmic, maxillary & mandibular). OPHTHALMIC NERVE ❖ It contains sensory fibers. ❖ Divides into 3 branches (lacrimal, frontal & nasociliary). They all pass through sup orbital fissure. Branches and Distribution: Branch Course, branches & distribution Lacrimal To lacrimal gland. Palpebral branch → upper lid Frontal Supratrochlear N → skin of forehead Supraorbital N → supraorbital foramen → skin of forehead Nasociliary Supply skin over bony & cartilaginous nose, cornea & ethmoidal & sphenoid air sinuses MAXILLARY NERVE ❖ It contains sensory fibers. ❖ Passes through foramen rotundum to inf orbital fissure. Branches and distribution: Branch Course, branches & distribution Meningeal Supply meninges Zygomatic Passes through inf orbital fissure Zygomaticofacial → skin of the cheek (upper part) Zygomaticotemporal → non hairy temporal region Sphenopalatine Supply the nose Pharyngeal Supply the pharynx Greater & lesser palatine Supply the palate Sup alveolar (post, middle & ant) Supply upper jaw & maxillary sinus Infraorbital Palpebral Lower lid Nasal Ala of nose Labial Upper lip Page | 33  Whitaker & Borley Mandibular nerve Page | 34  MANDIBULAR NERVE ❖ It contains sensory & motor fibers. ❖ Passes through foramen ovale. ❖ Divides into ant and post divisions. Branches and Distribution: Branch Course, branches & distribution Trunk Meningeal Reenter skull through foramen spinosum & supply meninges (nervus spinosus) N to med pterygoid Supply med pterygoid, tensor palati & tensor tympani Ant Ns to lat pterygoid Lat pterygoid division N to masseter Masseter Deep temporal Ns Temporalis Buccal Skin over buccinators Post Auriculotemporal Passes deep to neck of mandible division Supply outer surface of auricle & hairy temporal region Lingual Passes near the lower 3rd molar Supply ant 2/3 of the tongue with general sensations Joined by chorda tympani N (of facial) which supply the same area with taste Inf alveolar Gives mylohyoid N: runs in mylohyoid groove → supply mylohyoid and ant belly of digastric muscle Passes through mandibular foramen & supply lower teeth Emerges from mental foramen as mental N & supply chin & lower lip Page | 35  Whitaker & Borley Facial nerve Page | 36  FACIAL NERVE ❖ It is attached to pons. ❖ It contains motor, sensory, taste & parasympathetic fibers. ❖ It passes through internal auditory meatus → facial canal (in the petrous bone) → stylomastoid foramen → parotid gland. Branches and Distribution: Branch Course, branches & distribution Greater Arises in middle ear → passes through its foramen petrosal N Supply lacrimal gland, nose, pharynx & palate with parasympathetic fibers Supply palate with taste Chorda Arises in middle ear → passes to infratemporal fossa → join the lingual Tympani N (of mandibular) It supplies submandibular & sublingual salivary glands with parasympathetic fibers It supplies ant 2/3 of tongue with taste N to stapedius Arises in middle ear & supply stapedius Sensory branch Sensory to external ear Post auricular Occipital belly of occipitofrontalis Digastric Post belly of digastric Stylohyoid Stylohyoid muscle Temporal Frontal belly of occipitofrontalis & orbicularis oculi Zygomatic Muscles near zygomatic arch & orbicularis oculi Buccal Buccinators Mandibular Muscles of lower lip Cervical Platysma Control of facial motor nucleus: The cerebrum (through corticonuclear fibers) controls the whole facial motor nucleus of the opposite side. But it only controls the upper part of the nucleus of the same side. So, the upper part of the facial motor nucleus (supplying muscles of upper part of face) receives bilateral corticonuclear fibers, while the lower part (supplying muscles of lower part of face) receives only contralateral fibers. Accordingly: ⎯ Lesion above the facial motor nucleus will lead to paralysis of the muscles of lower part of opposite side only. ⎯ Lesion of the nucleus or the facial nerve will lead to paralysis of all the muscles of the same side. Page | 37 Glossopharyngeal nerve Vagus nerve Whitaker & Borley Page | 38  GLOSSOPHARYNGEAL NERVE ❖ It is attached to medulla. ❖ It contains motor, sensory, taste & parasympathetic fibers. ❖ It passes through jugular foramen. Branches and Distribution: Branch Course, branches & distribution Meningeal Reenter skull through jugular foramen & supply meninges Tympanic N Enters the middle ear → sensory innervation Continue as lesser petrosal N → foramen ovale → Parasympathetic to parotid gland N to stylopharyngeus Stylopharyngeus Pharyngeal branches Sensory to pharynx & tonsils Lingual branches Sensory & taste to post 1/3 of tongue VAGUS NERVE ❖ It is attached to medulla. ❖ It contains motor, sensory, taste & parasympathetic fibers. ❖ It passes through jugular foramen. Branches and Distribution (In the head & neck): Branches Course, branches & distribution Meningeal Reenter skull through jugular foramen & supply meninges Pharyngeal Its fibers are mainly from cranial accessory (through vagus) Supply all Ms of Pharynx except stylopharyngeus & all Ms of Palate except tensor palati Sup laryngeal N a) Internal laryngeal N: supply root of tongue & epiglottis (general & taste sensations) & larynx (general sensation) b) External laryngeal N: supply cricothyroid Recurrent The sensory fibers from vagus (supply the larynx) laryngeal N (Rt) The motor fibers from cranial accessory (through vagus) →supply all muscles of larynx except cricothyroid N.B.: The italic branches are branches of cranial accessory N (through vagus). External & recurrent laryngeal nerves are closely related to the arteries of thyroid gland & could be injured during thyroid operations. Injury of recurrent laryngeal N leads to hoarseness of voice, while injury of external laryngeal N leads to loss of high pitched voice. The vagus N gives other branches in thorax & abdomen (parasympathetic to viscera). Page | 39 Accessory nerve Whitaker & Borley Hypoglosssal nerve Page | 40  ACCESSORY NERVE CRANIAL ACCESSORY NERVE ❖ It is attached to medulla. ❖ It contains motor fibers only. ❖ It is joined by spinal accessory intracranial. ❖ It passes through jugular foramen, where spinal accessory separates from it. ❖ It joins the vagus N & distributes its fibers through branches of vagus. ❖ It supplies all muscles of pharynx except stylopharyngeus and all muscles of palate except tensor palati (through the pharyngeal branch of vagus). And supplies all muscles of Larynx except cricothyroid (through the recurrent laryngeal branch of vagus). SPINAL ACCESSORY NERVE ❖ It is not a cranial nerve, it is formed of fibers from C1-5 (ant rami). ❖ It enters the skull through foramen magnum → join the cranial accessory N → passes through jugular foramen → leaves the cranial accessory N. ❖ It supplies sternomastoid & trapezius. HYPOGLOSSAL NERVE ❖ It is attached to medulla. ❖ It contains motor fibers only. ❖ It passes through hypoglossal (ant condylar) foramen. Branches & distribution: It supplies all muscles of the tongue except (palatoglossus). N.B.: hypoglossal N is joined by fibers from C1. These fibers give the following branches: 1) Meningeal branch: supply meninges. 2) N to geniohyoid. 3) N to thyrohyoid. 4) Descendens hypoglossi: it joins descendens cervicalis (C2-3) to form ansa cervicalis, which supply all infrahyoid muscles except thyrohyoid. Control of hypoglossal nucleus: The cerebrum (through corticonuclear fibers) controls the hypoglossal nucleus of the opposite side, But not of the same side. Accordingly: ⎯ Lesion above the hypoglossal nucleus will lead to paralysis of the opposite hypoglossal nerve. ⎯ Lesion of the nucleus or the hypoglossal nerve will lead to paralysis of the nerve at the same side. Applied Anatomy: injury to hypoglossal N will lead to paralysis of genioglossus (responsible for deviation of tongue to opposite side), leading to a deviation of tongue to the same side. Page | 41  Neural tube Pinterest Development of brain Page | 42  Embryological Preview Neural tube ❖Formation of the neural tube: The central part of the ectoderm between primitive node and prechordal plate thickens to form neural plate. The neural plate invaginates to form neural groove, which has two neural folds on its sides. The junction between the ectoderm and the neural groove on each side shows a longitudinal strip called neural crest. The neural folds fuse with each other to form the neural tube. The neural tube separates from the surface ectoderm and sinks down below it but above the notochord. The neural crest becomes dorsolateral to the neural tube. The neural tube has two openings at its ends called the cranial and caudal neuropores, which close by the end of the 4th week. ❖Differentiation of the neural tube The lateral wall of the neural tube is thickened forming 2 lateral walls, each is further divided into: Basal lamina: ventral, develops into motor cells Alar lamina: dorsal, develops into sensory cells The cranial part of the neural tube enlarges and develops into the brain. While the caudal part develops into the spinal cord The enlarged cranial part shows 3 dilatations (brain vesicles): 1] Prosencephalon (forebrain): further develops into: a) Telencephalon: develops into cerebral hemispheres and its lumen becomes lateral ventricles b) Diencephalon: develops into (thalamus, hypothalamus and epithalamus). and its lumen becomes third ventricle 2] Mesencephalon: develops into the midbrain and its lumen becomes cerebral aqueduct. 3] Rhombencephalon: further divided into a) Metencephalon: develops into the pons b) Myelencephalon: develops into the medulla c) Cerebellum The alar laminae in the Rhombencephalon shifts laterally so that the lumen becomes posterior and widens forming the fourth ventricle. Accordingly, the alar laminae become lateral and the basal laminae become medial. Page | 43  Brain stem columns Pocketdentistry/ Basicmedicalkey Derivatives of neural crest Page | 44  In the brain stem, the alar lamina divides into 4 longitudinal sensory columns while the basal lamina divides into 3 longitudinal motor columns. These columns will further divide into cranial nerves nuclei and They are (from lat to med): 1] Special somatic afferent (GVA): develops into nuclei receiving auditory and equilibrium sensations. 2] General somatic afferent (GVA): develops into nuclei receiving somatic sensations. 3] Special visceral afferent (SVA): develops into a nucleus receiving taste sensation. 4] General visceral afferent (GVA): develops into nucleus receiving visceral sensations. 5] General visceral efferent (GVE): develops into nuclei supplying viscera with parasympathetic fibers. 6] Special visceral efferent (SVE): develops into nuclei supplying somatic muscles derived from pharyngeal arches. 7] Special efferent (SE): develops into nuclei supplying somatic muscles derived from somites. In the spinal cord, the lateral wall also divides into: Basal lamina: ventral, develops into the motor cells (ventral horns). Alar lamina: dorsal, develops into the sensory cells (dorsal horn). The caudal part of the spinal cord is stretched and transmitted into filum terninale. ❖Congenital anomalies: Hydrocephalus: enlarged ventricles (and skull) due to obstruction in the lumen of the neural tube (usually cerebral aqueduct). Anencephaly: failure of closure of the cranial neuropore. The cerebral hemisphere (as well as the covering skull vault) is not developed. Spina bifida: failure of fusion of the laminae of the vertebrae. It may be occult or accompanied by protrusion of meninges, spinal cord, or both. Meningocele: a meningeal sac protrudes through a vertebral defect, The neural tube develops normally. Meningomyelocele: part of spinal cord and meninges protrude through a vertebral defect. The neural tube is usually fused normally. Myelocele: the spinal cord is exposed through a vertebral defect. This is due to failure of fusion of the neural folds into neural tube. N.B.: the development of the neural tube is the inducer of the development of the surrounding skull and vertebral column. This is why combined congenital anomalies are common. ❖Derivatives of the neural crest Spinal dorsal root ganglia Sensory ganglia of cranial nerves Autonomic ganglia Suprarenal medulla (considered as a modified autonomic ganglion) Schwann cells (responsible for myelination of peripheral nerves Arachnoid and pia (the dura is derived from the sclerotomes) Melanoblasts of the skin Page | 45  levels of spinal segments Spinal cord and spinal nerve Page | 46  Central nervous system SPINAL CORD Length: 45 cm. Extent: Sup: at the lower border of foramen magnum. Inf: the lower end is called conus medullaris & at the following levels: 3rd month of intrauterine life: same length of vertebral column. At birth: L3 vertebra. After 3rd month: lower border of L1 vertebra (45 cm in adults). Segments & its levels 31 segments (8 C, 12 T, 5 L, 5 S & 1 Cc). From each segment arises a pair of spinal nerves. Levels: ⎯ Cervical segments = number of vertebra +1 (e.g.: C5 segment is at the level of C4 vertebra). ⎯ T1-T6 segments = number of vertebra +2. ⎯ T7-T12 segments = number of vertebra +3. ⎯ Lumbar segments: level of T10 & T11 vertebrae. ⎯ Sacral & coccygeal segments: level of T12 & L1 vertebrae. Spinal nerves 31 pairs (8 C, 12 T, 5 L, 5 S & 1 Cc). It has 2 roots: Post (dorsal) root (sensory) & ant (ventral) root (motor). The 2 roots unite to form the spinal nerve (mixed). The spinal nerve divides into 2 rami: Ant (ventral) ramus: ⎯ Mixed. ⎯ Form plexuses (except in thoracic region). ⎯ Supplies muscles & skin of anterolateral sides of trunk & limbs. Post (dorsal) ramus: ⎯ Mixed. ⎯ Does not form plexuses. ⎯ Supplies muscles & skin of the back (post to vertebral column). Important segmental innervation levels: ⎯ Skin just below xiphoid process is supplied by T7. ⎯ Skin around the umbilicus is supplied by T10. ⎯ Skin of inguinal region is supplied by L1 Page | 47  Nuclei of spinal cord Schuenke Lamination of spinal cord Page | 48 Cross section of the spinal cord ❖ White matter: formed of myelinated axons (ascending & descending tracts & crossing fibers). Ant columns (2): ant to grey matter. Lat columns (2): lat to grey matter. Post columns (2): post to grey matter. ❖ Grey matter: H shaped & consists mainly of nuclei (nerve cells within CNS). Post horns (2): sensory. Lateral horns (2): autonomic (some segments). Ant horns (2): motor. ❖ Central canal: contains CSF, Superiorly it is continuous with central canal of medulla. Lamination & nuclei of grey matter: Lamina Site & extent Corresponding nuclei Function I Post horn (tip) of all Posteromarginal nucleus Pain & temperature segments II All segments Substantia gelatinosa (of Pain modulation Rolandi) III All segments Main sensory nucleus Touch & pressure IV (nucleus proprius) Pain V Post horn (neck) Proprioception VI Post horn (base) VII Between ant & post horns Dorsal (Clarke’s) nucleus Unconscious proprioception of T1-L3 segments Between ant & post horns Spinal border nucleus Unconscious proprioception of L1-S3 segments T1-L3 & S2-4 segments Intermediolateral nuclei Autonomic (gives preganglionic efferent fibers) T1-L3 & S2-4 segments Intermediomedial nuclei Autonomic (receives visceral sensations) VIII Ant horn (med) of all Commissural nucleus Interneurons which relay in segments lamina IX All segments Dorsomedial nucleus Supplies trunk flexors & proximal limb muscles All segments Ventromedial nucleus Supplies trunk extensors C5-T1 & L1-S3 Dorsolateral nucleus Supplies limb flexors C5-T1 & L1-S3 Ventrolateral nucleus Supplies limb extensors IX Ant horn (lat) AHCs X Around central canal Grisea centralis Glial cells Gate pain modulation: substantia gelatinosa receives impulses from Gracile, Cuneate, lat spinothalamic & corticospinal tracts & many CNS nuclei. Substantia gelatinosa cells secrete enkephalins which inhibit impulses from pain fibers of dorsal root ganglia (DRG) to posteromarginal & main sensory nuclei (lat spinothalamic tract). Page | 49 External features of brain stem (Ant) Schuenke External features of brain stem (post) Page | 50  BRAIN STEM EXTERNAL FEATURES OF BRAIN STEM ❖ Medulla: Ant (from med to lat): Ant median fissure. Pyramid: marking pyramidal tract. Anterolateral fissure: attachment of 12th cranial N. Olive: marking inf olivary nucleus. Posterolateral fissure: attachment of 9th 10th & 11th cranial Ns. Inf cerebellar peduncle: connecting medulla to cerebellum. Post & sup: Medullary stria: between pons & medulla. Inf fovea: inverted V shaped depression marking nuclei of 12th cranial nerve (med), 10th (deep) & 8th (lat). Post & inf (from med to lat): Post median fissure. Gracile tract & nucleus. Cuneate tract & nucleus. ❖ Pons: Ant (from med to lat): Median groove: for basilar A. Transverse ridges: marking transverse pontine fibers, it shows attachment of 5th cranial N, the 6th cranial N is at its inf border. Middle cerebellar peduncle: connecting pons to cerebellum. Pontocerebellar angle: between pons, medulla & cerebellum, it is site of attachment of 7th & 8th cranial Ns. Post (from med to lat): Median fissure. Medial eminence & facial colliculus: facial colliculus is caused by fibers of facial N encircling 6th cranial N nucleus. ❖ Midbrain: Ant (from med to lat): Interpeduncular fossa: site of attachment of 3rd cranial N. Cerebral peduncles: marking pyramidal tract. Post & sup: 2 sup colliculi: concerned with visual reflexes. Post & inf: 2 inf colliculi: concerned with auditory reflexes. Below inf colliculi is the site of attachment of 4th cranial N. Page | 51  Schuenke Cranial nerves nuclei Page | 52  CRANIAL NERVES TYPES OF FIBERS & NUCLEI ❖ Types of fibers: Cranial nerves has 7 types of fibers. Their nuclei in brain stem are arranged in 7 longitudinal columns, they are (from lat to med): Fibers Function Cranial nerves SSA Vision, hearing & equilibrium 2&8 GSA General sensations 5,7,9 & 10 SVA Taste & smell 1 & solitary nucleus (7,9 &10) GVA Visceral sensations Solitary nucleus (9 &10) GVE Parasympathetic efferent 3,7,9 & 10 SVE Supply somatic muscles 5,7 & Ambiguous nucleus (9,10,11) SE Supply somatic muscles 3,4,6 & 12 ❖ Cranial nerves nuclei: Cranial nerve Attachment Fibers Nuclei Function 1 Olfactory Cerebrum SVA --- smell 2 Optic Cerebrum SSA --- vision 3 Oculomotor Mid brain GVE Edinger Westphal Parasympathetic to eye SE Oculomotor Motor to eye 4 Trochlear Mid brain SE Trochlear Motor to eye 5 Trigeminal Pons GSA Spinal trigeminal Sensory to face Main sensory Mesencephalic SVE Trigeminal motor Motor to muscles of mastication, tensor tympani, tensor palati, mylohyoid & ant belly of digastric 6 Abducent Pons SE Abducent Motor to eye 7 Facial Pons GSA Spinal trigeminal Sensory to external ear SVA Solitary Taste from ant 2/3 of tongue GVE Special lacrimal Parasympathetic to lacrimal glands, Sup salivary orbit, nose, palate & pharynx & Submandibular & sublingual glands SVE Facial Motor to muscles of face & scalp, platysma, post. belly of digastric & stylohyoid 8 Vestibulocochlear Pons SSA Vestibular equilibrium Cochlear Hearing 9 Glossopharyngeal Medulla GSA Spinal trigeminal Sensory to post 1/3 of tongue & pharynx SVA Solitary Taste to post 1/3 of tongue GVA Solitary Visceral sensations GVE Inf salivary Parasympathetic to parotid SVE Ambiguous Motor to stylopharyngeus 10 Vagus Medulla GSA Spinal trigeminal Sensory to root of tongue & larynx SVA Solitary Taste to root of tongue GVA Solitary Visceral sensations GVE Dorsal motor Parasympathetic to viscera SVE Ambiguous Motor to cricothyroid 11 Cranial accessory Medulla SVE Ambiguous Motor to most of muscles of palate, pharynx & larynx 12 Hypoglossal Medulla SE Hypoglossal Motor to muscles of tongue (except palatoglossus) Page | 53 Cerebrum (external features of superolateral surface ) Schuenke Cerebrum (external features of med & inf surfaces ) Page | 54  CEREBRUM FEATURES OF CEREBRAL HEMISPHERE ❖ The cerebral hemisphere has 3 surfaces (lat, med & inf), it shows fissures (sulci) & lobes in between (gyri). It is divided into 4 main lobes (frontal,