1. Nervous system Afferent: Sensory Receive Efferent: Motor Integrative:

2. Functions of nervous system Receive: receptors, sensory neurons Store: spinal cord, brain Integrate: spinal cord, brain Create new complexes: brain Respond: motor neurons, muscles, glands Regulate Protect

3. Sensory, Motor and Integrative Systems

6. Cerebral Blood Flow, Cerebral Spinal Fluid

7. Blood Flow to the Brain Blood Flow to the Brain
brain is highly dependent on blood flow
cessation of flow for 5-10 seconds results in a loss of consciousness
highly dependent on oxygen delivery

8. Cerebral Blood Flow Blood Flow to the Brain
15% of the resting cardiac output ( ml/min)
related to the metabolic rate of the brain
3 metabolic factors have potent effects on blood flow
CO2 H+ O2

9. Cerebral Blood Flow An increase in CO2 increases blood flow.
This is thought to work through an increase in the H+ ion concentration.
CO2 + H2O → H2CO3 → H+ + HCO3-
An increase in H+ concentration depresses neuronal activity.
Normal PO mm Hg.
Below 30 mm Hg begin to see increase in flow, below 20 mm Hg coma.

10. Cerebral Blood Flow Cerebral Blood Flow
cerebral blood flow is autoregulated
nearly constant over a pressure range of 60 to 140 mm Hg
below 60 mm Hg blood flow begins to fall rapidly
above 140 mm Hg the blood flow increases but most importantly the blood vessels begin to stretch, which can lead to damage and eventual rupture (stroke)

11. Cerebrospinal fluid (CSF) Site Composition Circulation Functions

12. Cerebrospinal Fluid (CSF)
Clear fluid.
Circulates through cavities in the brain (ventricles) and the spinal cord (central canal) and also in the subarachnoid space.
Absorbs shock and protects the brain and the spinal cord.
Helps transport nutrients and wastes from the blood and the nervous tissue.

13. Formation and Circulation of CSF in the Ventricles
Choroid plexuses- networks of capillaries in the walls of the ventricles.
Ventricles are lined by ependymal cells.
Plasma is drawn from the choroid plexuses through ependymal cells into the ventricles to produce CSF.

14. Cerebrospinal fluid (CSF) volume: ml (wt in pounds) contains: (glucose, proteins, H+, Na+, k+, Ca++, Mg++, Cl- HCO3-,

15. Cerebrospinal fluid (CSF) Mechanical Protection: shock absorber Chemical: homeostasis Circulation

16. Cerebrospinal fluid (CSF) HYDROCEPHALUS

19. Circulation of CSF
CSF from the lateral ventricles → interventricular foramina → third ventricle → cerebral aqueduct → fourth ventricle → subarachnoid space or central canal.
CSF is reabsorbed into the blood by arachnoid villi.

20. highly metabolic organ
Brain Metabolism
highly metabolic organ
2% of total body mass, yet has 15% of total metabolism of the body
limited anaerobic metabolism
anaerobic breakdown of glycogen cannot supply the energy requirements of the brain
most neuronal activity depends on the second by second delivery of oxygen to the brain

21. mostly glucose dependent
Brain Metabolism
mostly glucose dependent
uptake of glucose into the brain is not dependent on insulin
blood glucose must be maintained for the brain to receive the proper amount of this substrate

23. Nervous system Afferent: Sensory Receive Efferent: Motor Integrative:

24. Functions of nervous system Receive: receptors, sensory neurons Store: brain , spinal cord Integrate: brain, spinal cord Create new complexes Respond: Motor neurons, muscles, glands Regulate Protect

25. Classification of Sensory Receptors Based on the Location
Exteroceptors
Interoceptors
Proprioceptors

26. Sensation
Conscious and subconscious awareness of changes in the external or internal environment.
Components of sensation: Stimulation of the sensory receptor → transduction of the stimulus → generation of nerve impulses → integration of sensory input.

27. Classification of Sensory Receptors based on the type of Stimulus
Mechanoreceptors
Thermoreceptors
Nociceptors
Photoreceptors
Chemoreceptors
Osmoreceptors

28. Classification of Sensory Receptors
General senses: somatic and visceral.
Somatic- tactile, thermal, pain and proprioceptive sensations.
Visceral- provide information about conditions within internal organs.
Special senses- smell, taste, vision, hearing and equilibrium or balance.

29. Sensation
Each of the principle types sensation; touch, pain, sight, sound, is called a modality of sensation.
Each receptor is responsive to one type of stimulus energy. Specificity is a key property of a receptor, it underlines the most important coding mechanism, the labeled line.
How the sensation is perceived is determined by the characteristics of the receptor and the central connections of the axon connected to the receptor.

30. Sensory Receptors in the Skin

31. Types of Sensory Receptors
Free nerve endings: pain and thermoreceptors.
Encapsulated nerve endings: pacinian corpuscles.
Separate cells: hair cells, photoreceptors and gustatory receptor cells.

32. Generator Potential and Receptor Potential
Generator potential is produced by free nerve endings, encapsulated nerve endings, and olfactory receptors. When it reaches a threshold, it triggers one or more nerve impulses in the axon of a first-order sensory neuron.
Receptor potential triggers the release of neurotransmitter → postsynaptic potential → action potential.

33. Sensory Receptors and their Relation-ship to First-Order Sensory Neurons

34. Somatic Sensations
Sensory receptors in the skin (cutaneous sensations), muscles, tendons and joints and in the inner ear.
Uneven distribution of receptors.
Four modalities: tactile, thermal, pain and proprioceptive.

35. Receptor Excitation
Figure 46-3; Guyton & Hall

36. Relationship between Receptor Potential and Action Potentials
Figure 46-2; Guyton & Hall

37. Adaptation of Sensory Receptors
Rapidly adapting receptors: receptors that detect pressure, touch and smell.
Slowly adapting receptors: receptors that detect pain, body position, and chemical composition of the blood.

38. Adaptation of Receptors
When a continuous stimulus is applied, receptors respond rapidly at first, but response declines until all receptors stop firing.

39. Adaptation Rate of adaptation varies with type of receptor.
Therefore, receptors respond when a change is taking place (i.e., think of the feel of clothing on your skin.)

40. Mechanism of Adaptation
varies with the type of receptor
photoreceptors change the amount of light sensitive chemicals
mechanoreceptors redistribute themselves to accommodate the distorting force (i.e., the pacinian corpuscle)
some mechanoreceptors adapt slowly, some adapt rapidly

41. Slowly Adapting (Tonic) Receptors
continue to transmit impulses to the brain for long periods of time while the stimulus is present
keep brain apprised of the status of the body with respect to its surroundings
will adapt to extinction as long as the stimulus is present, however, this may take hours or days
these receptors include: muscle spindle, golgi tendon apparatus, Ruffini’s endings, Merkels discs, Macula, chemo- and baroreceptors

42. Rapidly Adapting (Phasic) Receptors
respond only when change is taking place
rate and strength of the response is related to the rate and intensity of the stimulus
important for predicting the future position or condition of the body
very important for balance and movement
types of rapidly adapting receptors: pacinian corpuscle, semicircular canals

43. Fig

44. Transmission of Receptor Information to the Brain
the larger the nerve fiber diameter the faster the rate of transmission of the signal
velocity of transmission can be as fast as 120 m/sec or as slow as 0.5 m/sec
nerve fiber classification
type A - myelinated fibers of varying sizes, generally fast transmission speed
subdivided into a, b, d, g
type C - unmyelinated fibers, small with slow transmission speed

46. Importance of Signal Intensity
Signal intensity is critical for interpretation of the signal by the brain (i.e., pain).
Gradations in signal intensity can be achieved by:
1) increasing the number of fibers stimulated, spatial summation
2) increasing the rate of firing in a limited number of fibers, temporal summation.

47. Signal Intensity An example of spatial summation
Figure 46-7; Guyton & Hall

48. Relaying Signals through Neuronal Pools

49. Neuronal Pools
groups of neurons with special characteristics of organization
comprise many different types of neuronal circuits
converging
diverging
reverberating

50. Modified from figures 46-11 and 46-12; Guyton & Hall
Neuronal Pools
Modified from figures and 46-12; Guyton & Hall

51. Neuronal Pools
Lateral inhibition

52. Reverberating Circuits
Figure 46-14;
Guyton & Hall

53. Classification of Somatic Sensations
Mechanoreceptive - stimulated by mechanical displacement
tactile
touch
pressure
vibration
tickle and itch
position or proprioceptive
static position
rate of change

54. Classification of Somatic Sensations
Thermoreceptive
detect heat and cold
Nociceptive
detect pain and are activated by any factor that damages tissue

55. Tactile Sense Transmission
Meissner’s corpuscles, hair receptors, Pacinian corpuscles and Ruffini’s end organs transmit signals in type Ab nerve fibers at m/sec.
Free nerve endings transmit signals in type Ad nerve fibers at 5-30 m/sec, some by type C unmyelinated fibers at m/sec.
The more critical the information the faster the rate of transmission.

56. Pathways for the Transmission of Sensory Information
Almost all sensory information enters the spinal cord through the dorsal roots of the spinal nerves.
Two pathways for sensory information
dorsal column-medial lemniscal system
anterolateral system

57. Dorsal Column System
Contains large myelinated nerve fibers for fast transmission ( m/sec).
High degree of spatial orientation maintained throughout the tract.
Transmits information rapidly and with a high degree of spatial fidelity (i.e., discrete types of mechanoreceptor information).
Touch, vibration, position, fine pressure

58. The Dorsal Column System

59. The Posterior Column-Medial Lemniscus Pathway
Conveys nerve impulses for touch, pressure, vibration and conscious proprioception from the limbs, trunk, neck, and posterior head to the cerebral cortex.

60. The Somatosensory Cortex
Figure 47-6; Guyton and Hall

61. Anterolateral System
Smaller myelinated and unmyelinated fibers for slow transmission ( m/sec)
Low degree of spatial orientation
Transmits a broad spectrum of modalities
Pain, thermal sensations, crude touch and pressure, tickle and itch, sexual sensations.

62. The Anterolateral (spinothalamic) pathway
Conveys nerve impulses for pain, cold, warmth, itch, and tickle from the limbs, trunk, neck, and posterior head to the cerebral cortex.

63. Figure 47-13;
Guyton and Hall

64. Somatic Sensory Cortex
Located in the postcentral gyrus
Highly organized distinct spatial orientation
Each side of the cortex receives information from the opposite side of the body
Unequal representation of the body
lips have greatest area of representation followed by the face and the thumb
trunk and lower body have the least area

65. Figure 47-7; Guyton and Hall

66. Cellular Organization of the Cortex
Six separate layers of neurons with layer I near the surface of the cortex and layer VI deep within the cortex.
Incoming signals enter layer IV and spread both up and down.
Layers I and II receive diffuse input from lower brain centers.

67. Cellular Organization of the Cortex
Layer II and III neurons send axons to closely related portion of the cortex presumably for communicating between similar areas.
Layer V and VI send axons to more distant parts of the nervous system, layer V to the brainstem and spinal cord, layer VI to the thalamus.

68. Diffuse lower input Related brain areas Incoming signals
To brainstem and cord
To thalamus
Figure 47-08; Guyton and Hall

69. Cellular Organization of the Cortex
Within the layers the neurons are also arranged in columns.
Each column serves a specific sensory modality (i.e., stretch, pressure, touch).
Different columns interspersed among each other.
interaction of the columns occurs at different cortical levels which allows the beginning of the analysis of the meaning of the sensory signals

70. Function of the Somatic Sensory Cortex
Destruction of somatic area I results in:
loss of discrete localization ability
inability to judge the degree of pressure
inability to determine the weight of an object
inability to determine the shape or form of objects, called astereognosis
inability to judge texture

71. Somatic Association Areas
Located behind the somatic sensory cortex in the parietal area of the cortex.
Association area receive input from somatic sensory cortex, ventrobasal nuclei of the thalamus, visual and auditory cortex.
Function is to decipher sensory meaning.
Loss of these areas results in the inability to recognize complex objects and loss of self.

72. Special Aspects of Sensory Function
Thalamus has some ability to discriminate tactile sensation.
Thalamus has an important role in the perception of pain and temperature.

73. Special Aspects of Sensory Function
Corticofugal fibers
fibers from the cortex to the sensory relay areas of thalamus, medulla and spinal cord
these fibers are inhibitory, they can suppress the sensory input
function to decrease the spread of a signal and sharpen the degree of contrast and adjust the sensitivity of the system

74. Pain

75. Pain occurs whenever tissue is being damaged
protective mechanism for the body
causes individual to remove painful stimulus
two types of pain, fast pain and slow pain
fast pain felt within 0.1 sec of the stimulus and is sharp in character
slow pain begins after a second or more and is throbbing or aching in nature

76. Pain Receptors and Their Stimulation
all pain receptors are free nerve endings
can be stimulated by:
mechanical (stretch)
thermal
chemical
bradykinin, serotonin, histamine, potassium ions, acids, acetylcholine and proteolytic enzymes
prostaglandins and substance P enhance the sensitivity of pain endings but do not directly excite them

77. Pain Receptors and Their Stimulation
pain receptors do not adapt to the stimulus
the rate of tissue damage is the cause of pain (most individuals feel pain at 450 C)
extracts from damaged tissue cause pain when injected under the skin
bradykinin causes the most pain and may be the single agent most responsible for causing the tissue damage type of pain
also the local increase in potassium ion concentration and action of enzymes can contribute to pain

78. Dual Pain Pathways
Fast pain is transmitted by type Ad fibers (velocity 6-30 m/sec).
Slow pain is transmitted by type C fibers ( m/sec).
Fast pain fibers are transmitted in the neospinothalamic tract.
Slow pain fibers are transmitted in the paleospinothalamic tract.

79. Neo- spinothalamic tract Paleo- spinothalamic tract
Figure 48-2; Guyton & Hall
Copyright © 2006 by Elsevier, Inc.

80. Neospinothalamic Tract
On entering the cord, pain fibers may travel up or down 1-3 segments and terminate on neurons in the dorsal horn.
2nd neuron crosses immediately to the opposite side and passes to the brain in the anterolateral columns.
Some neurons terminate in the reticular substance but most go all the way to the ventrobasal complex of the thalamus.
3rd order neurons go to the cortex.

81. Neospinothalamic Tract (cont’d)
Fast-sharp pain can be localized well.
However, fast pain fibers must be stimulated with other tactile receptors for the pain to be highly localized.

82. Paleospinothalamic Tract
Type C pain fibers terminate in laminae II and III of the spinal cord and make one or two local connections before giving rise to 2nd order neurons which cross immediately and pass to the brain in the anterolateral columns.
Only 10 to 25 % of the fibers terminate in the thalamus.
Most terminate diffusely in the:
reticular nuclei of the medulla, pons and mesencephalon
tectal area of the mesencephalon
periaqueductal gray region.

83. Paleospinothalamic Tract
lower terminations important to appreciate the suffering type of pain
from the lower reticular areas of the brain stem neurons project to the intralaminar nuclei of the thalamus, hypothalamus and other basal brain regions
poor localization of slow pain, often to just the affected limb or part of the body

84. Paleo- Neo- spinothalamic spinothalamic tract tract
Figure 48-3; Guyton & Hall

85. The Appreciation of Pain
Removal of the somatic sensory areas of the cortex does not destroy the ability to perceive pain.
Pain impulses to lower areas can cause conscious perception of pain.
Therefore, cortex probably important for determining the quality of pain.
Stimulation of the reticular areas of the brain stem and intralaminar nuclei of thalamus (where pain fibers terminate) causes widespread arousal of the nervous system.

86. Analgesia System of the Brain and Spinal Cord
The brain has the capability to suppress pain fibers.
Periaqueductal gray area neurons send axons to the nucleus raphe magnus and the nucleus paragigantocellularis.
Raphe magnus and paragigantocellularis neurons send axons to the dorsal horns of the spinal cord.
These neurons activate a pain inhibitory complex in the spinal cord.

87. Analgesia system of the brainstem and spinal cord
Figure 48-4;
Guyton & Hall

88. Analgesia System of the Brain and Spinal Cord
Higher brain levels, the periventricular nuclei of the hypothalamus and the medial forebrain bundle can activate the periaqueductal gray region and suppress pain.

89. Pain Suppression Mechanism
Nerve fibers in the periventricular nucleus and the periaqueductal gray secrete enkephalin at their nerve endings.
Nerve fibers from the raphe magnus secrete serotonin at their nerve endings.
The serotonin causes the local neurons to secrete enkephalin.
Enkephalin is believed to cause both pre- and post-synaptic inhibition of type C and type Ad pain fibers where they synapse in the dorsal horns.

90. Endogenous Opiate Systems
In the early 1970’s it was discovered that an injection of minute quantities of morphine into the area around the third ventricle produced a profound and prolonged analgesia.
This started the search for “morphine receptors” in the brain.
Several “opiate-like” substances have been identified. All are breakdown products of three large molecules; proopiomelanocortin, proenkephalin, and prodynorphin.

91. Endogenous Opiate Systems
The major opiate substances; b-endorphin, met-enkephalin, leu-enkephalin, dynorphin
The enkephalins and dynorphin are found in the brain stem and spinal cord.
The b-endorphin is found in the hypothalamus and the pituitary.

92. Function of the Opiate System
pain suppression during times of stress
an important part of an organism’s response to an emergency is a reduction in the responsiveness to pain
effective in defense, predation, dominance and adaptation to environmental challenges

93. Pain and Tactile Fibers
Stimulation of large type Ab sensory fibers from peripheral tactile receptors can depress the transmission of pain signals, “the gate control hypothesis”.
Mechanism is a type of lateral inhibition of the pain fiber by the sensory fiber.
Mechanism of action of massage, liniments, electrical stimulation of the skin

95. Referred and Visceral Pain
Pain from an internal organ that is perceived to originate from a distant area of the skin.
Mechanism is thought to be intermingling of second order neurons from the skin and the viscera.
Viscera have few sensory fibers except for pain fibers.
Highly localized damage to an organ may result in little pain, widespread damage can lead to severe pain.

96. Referred and Visceral Pain
localized to the dermatome of embryological origin
heart localized to the neck, shoulder and arm
stomach localized to the above the umbilicus
colon localized to below the umbilicus

97. Referred Pain From the Viscera
Figure 48-6;
Guyton & Hall

98. Causes of Visceral Pain
ischemia
chemical irritation
spasm of a hollow viscus
over distension of a hollow viscus

99. Headache Pain Brain tissue itself is insensitive to pain
Pain sensitive structures of the brain are the membranes that cover the brain and the blood vessels:
dura
blood vessels of the dura
venous sinuses
middle meningeal artery

100. Origin of Headache Pain
Figure 48-9; Guyton & Hall

101. Intracrainial Headache
meningitis
inflammation of the meninges resulting in a severe headache
migraine
results from abnormal vascular phenomenon
vasospasm followed by prolonged vasodilation
vasodilation causes stretching of the coverings of the blood vessels
hangover
irritation of the meninges by alcohol breakdown products and additives

102. Extracranial Headache
muscular spasm, tension headache
emotional tension may cause tension of muscles attached to the neck and scalp which causes irritation of scalp coverings
sinus headache
irritation of nasal structures
eye strain
excessive contraction of the ciliary muscle in an attempt to focus, contraction of facial muscles

103. Thermal Sensations many more cold receptors than warm receptors
density of cold receptors varies
highest on the lips, lowest on the trunk
freezing cold and burning hot are the same sensation because of stimulation of pain receptors

104. Stimulation of Thermal Receptors
Cold receptors respond from 7 to 44o C with the peak response at 25o C.
Warm receptors respond from 30 to 49o C with the peak response at 44o C.
The relative degree of stimulation of the receptors determines the temperature sensation.
Thermal receptors adapt to the stimulus but not completely.

105. Stimulation of Thermal Receptors
Figure 48-10; Guyton & Hall

106. Mechanism of Stimulation
Cold or warm is thought to change the metabolic rate of the receptor.
This changes the rate of intracellular reactions.

107. Somatic Motor Pathways
Upper motor neurons → lower motor neurons → skeletal muscles.
Neural circuits involving basal ganglia and cerebellum regulate activity of the upper motor neurons.

108. Organization of the Upper Motor Neuron Pathways
Direct motor pathway- originates in the cerebral cortex.
Corticospinal pathway: to the limbs and trunk.
Corticobulbar pathway: to the head.
Indirect motor pathway- originates in the brain stem.

109. Mapping of the Motor Areas
Located in the precentral gyrus of the frontal lobe.
More cortical area is devoted to those muscles involved in skilled, complex or delicate movements.

110. The Corticospinal Pathways