prepared by MD, PhD, Associate Professor. Marta R. Gerasymchuk. Pathophysiology department of Ivano-Frankivsk National Medical University

1. Pathophysiology of thePathophysiology of the
nervous system: violation ofnervous system: violation of
sensory, motor and trophicsensory, motor and trophic
function.function.

2. Actuality of the lectureActuality of the lecture
 The nervous system as a main regulatory system of an organism in this orThe nervous system as a main regulatory system of an organism in this or
that measure participates in pathogenesis of each diseases. The earliest andthat measure participates in pathogenesis of each diseases. The earliest and
obligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology is
defensive and adaptive the response. The protective reflexes (cough,defensive and adaptive the response. The protective reflexes (cough,
vomiting), protective inhibition, response hypotalamo-hypophysial-adrenalvomiting), protective inhibition, response hypotalamo-hypophysial-adrenal
system belong to such responses.system belong to such responses.
 At the same time during development of diseases the nervous systemAt the same time during development of diseases the nervous system
becomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive the
response of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes a
source of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving and
character of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization of
pathological process and appear as a complex of diverse symptoms.pathological process and appear as a complex of diverse symptoms.
Frequently there is a pain, which on the essence is typical pathologicalFrequently there is a pain, which on the essence is typical pathological
process, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. The
disturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internal
organs.organs.
 The fundamental knowledges of the reasons and mechanisms of disordersThe fundamental knowledges of the reasons and mechanisms of disorders
motor, sensitive and trophic functions of the nervous system are necessary formotor, sensitive and trophic functions of the nervous system are necessary for
understanding of pathogenesis nervous diseases, and also many symptomsunderstanding of pathogenesis nervous diseases, and also many symptoms
of a damage of internal organs.of a damage of internal organs.

3. CONTENTCONTENT
• Nervous System: NeuronsNervous System: Neurons
• Division of the Nervous SystemDivision of the Nervous System
• Pain: features of pain as a kind of sensitivity.Pain: features of pain as a kind of sensitivity.
Etiology and pathogenesis of pain.Etiology and pathogenesis of pain.
• Antinociceptive systemsAntinociceptive systems
• Upper Motor NeuronsUpper Motor Neurons and Disordersand Disorders
• Sensory LossSensory Loss
• Spinal Cord InjuriesSpinal Cord Injuries
• DysphasiaDysphasia
• Diseases of the Basal GangliaDiseases of the Basal Ganglia

4. FunctionFunction of neuronsof neurons
 A). Sensory inputA). Sensory input
 B). IntegrationB). Integration
 C). ResponseC). Response

5. A). Non nervousA). Non nervous or glial cellsor glial cells..
1). Astrocytes1). Astrocytes
2). Microglia2). Microglia
3). Ependymal3). Ependymal
4). Oliodendrocytes4). Oliodendrocytes
5). Satellite cells5). Satellite cells
6).6). Schwann cellsSchwann cells form myelin sheathsform myelin sheaths
Types of cellsTypes of cells

6. Types ofTypes of
cellscellsB). NeuronsB). Neurons
1). Structure1). Structure
II).). cell bodycell body oror somasoma -- endoplasmicendoplasmic
reticulum called thereticulum called the nissl bodynissl body..
IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves)
a).a). Dendrites:Dendrites: input regioninput region
b).b). Axon:Axon: Carries information awayCarries information away
c).c). Synaptic knobsSynaptic knobs oror AxonalAxonal
terminalsterminals.. ReleasesReleases
neurotransmitters.neurotransmitters.
2).2). AxonsAxons
a).a). myelin sheathmyelin sheath -- protects andprotects and
electrically insulates fibers conductelectrically insulates fibers conduct
nerve impulses faster thannerve impulses faster than
nonmylenated fibers.nonmylenated fibers.
b).b). nodes of Ranviernodes of Ranvier::
spaces between the sheathsspaces between the sheaths
The action potential skips to the nodesThe action potential skips to the nodes

7. Nerve ImpulseNerve Impulse
A). TermsA). Terms
1).1). Resting membrane PotentialResting membrane Potential::
 PolarizedPolarized
2).2). DepolarizationDepolarization::
 Change in ion concentrationChange in ion concentration
3).3). HyperpolarizationHyperpolarization
 Change in ion concentration insideChange in ion concentration inside
becomes more negativebecomes more negative
4).4). Graded PotentialGraded Potential
 Localized change in ion; subthresholdLocalized change in ion; subthreshold
5).5). Action PotentialAction Potential
 Change in ion concentration thatChange in ion concentration that
does not decrease over distance.does not decrease over distance.
B).B). Action PotentialAction Potential
Stages of an Action PotentialStages of an Action Potential
polarized resting potentialpolarized resting potential
depolarizesdepolarizes
repolarizesrepolarizes
undershoot phaseundershoot phase
UndershooUndershoott :: the K+ channels stay openthe K+ channels stay open
once resting potential is reached;once resting potential is reached;
hyperpolarizing the cell.hyperpolarizing the cell.

8. NerveNerve ImpulseImpulse
C).C). PropagationPropagation
 Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane has
reached resting potential. The action potential moves at areached resting potential. The action potential moves at a
constant velocityconstant velocity
D).D). All or none phenomenonAll or none phenomenon
 Not all depolarizations result in action potentialsNot all depolarizations result in action potentials.. TheThe
depolarization must reach thedepolarization must reach the threshold pointthreshold point
E).E). Refractory periodRefractory period
 AAbsolute refractory periodbsolute refractory period cannot respond to anothercannot respond to another
stimuli.stimuli.
 RRelative refractory periodelative refractory period -- tthe threshold is higherhe threshold is higher
F). Impulse VelocityF). Impulse Velocity
 Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Not
stronger impulses or fasterstronger impulses or faster

9. SynapseSynapse –– junction that carriesjunction that carries
information between neuronsinformation between neurons
 A). TypesA). Types
1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction
2). Chemical synapse2). Chemical synapse
 neurotransmittersneurotransmitters
B). Termination of neurotransmitterB). Termination of neurotransmitter
 1). Degradation enzymes1). Degradation enzymes
 2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed
 3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitter
ImpulseImpulse
releasesreleases Ca++ (in neuron)Ca++ (in neuron)
± neurotransmitter released ± binds to receptors± neurotransmitter released ± binds to receptors ±±
ion channels open on postsynaptic membraneion channels open on postsynaptic membrane

10. A). Excitatory Synapses
 neurotransmitters results in the
depolarization of postsynaptic
membrane. Creating localized graded
response.
 (dendrites do not have action
potentials)
 IF THE GRADED RESPONSE IS
STRONG ENOUGH TO BE CARRIED
TO THE AXON A FULL ACTION
POTENTIAL WILL RESULT
B). Inhibitory Synapses
 Binding neurotransmitters reduces
the postsynaptic membranes ability
to create an action potential.
Induces hyperpolarization.
Types of Neurotransmitters

11. C. Integration or Summation of Synaptic Events
 It takes more than one synaptic event to create
an action potential.
 Presynaptic inhibition = excitatory
neurotransmitter by one neuron + inhibitory
neurotransmitter of another neuron

12. Neurotransmitters
A). Acetylcholine (ACh)
B). Biogenic Amines
• 1). Dopamine
• 2). Norepinephrine
• 3). Epinephrine
• 4). Serotonin
C). Amino Acids
D). Peptides
• 1). endorphins
E). Novel or Miscellaneous

13. Division of the Nervous
System
A). Central Nervous
System: (CNS)
• Brain and Spinal Cord
only
B). Peripheral Nervous
System
• Outside CNS
1). Sensory or afferent
division:
• Carries impulses to CNS
2). Motor or efferent
division
• Carries impulses from the
CNS.
I). Somatic Nervous System
• voluntary
II). Autonomic Nervous
System
• involuntary
• a. Parasympathetic
• b. Sympathetic

14. The SympatheticThe Sympathetic
Nervous SystemNervous System
 TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called the
preganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbar
regions of the spine.regions of the spine.
 Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoins
other preganglionic fibersother preganglionic fibers to form anto form an autonomic ganglionautonomic ganglion..
 At this point, theAt this point, the preganglionic fiber synapsespreganglionic fiber synapses on theon the
second nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,,
andand releases acetylcholinereleases acetylcholine, which causes the, which causes the
postganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential..
 From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travels
to itsto its target organtarget organ, the muscle or gland., the muscle or gland.
 TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases the
neurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors for
norepinephrinenorepinephrine are calledare called adrenergic receptorsadrenergic receptors..

15. The Parasympathetic Nervous SystemThe Parasympathetic Nervous System
 The fibers of the parasympathetic nervous systemThe fibers of the parasympathetic nervous system (PNS)(PNS)
leave the brain in the cranial nervesleave the brain in the cranial nerves oror leave the spinal cordleave the spinal cord
from the sacral areafrom the sacral area..
 TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travels
to an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ..
 Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholine
thatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber..
 TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a short
distancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nerve
also releases acetylcholinealso releases acetylcholine..
 Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic and
parasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors ..
 Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinic
receptorsreceptors. These names relate to the experimental. These names relate to the experimental
stimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(a
mushroom poison).mushroom poison).

16. Functions of the Sympathetic andFunctions of the Sympathetic and
Parasympathetic NervesParasympathetic Nerves
 TheThe sympathetic nervous systemsympathetic nervous system innervates theinnervates the heartheart,,
causing ancausing an increase in heart rateincrease in heart rate andand strength of contractionstrength of contraction..
 Sympathetic nervesSympathetic nerves innervateinnervate all large and small arteriesall large and small arteries
andand veinsveins, causing, causing constriction of all vesselsconstriction of all vessels except theexcept the
arterioles supplying skeletal musclearterioles supplying skeletal muscle..
 Sympathetic nervesSympathetic nerves innervate theinnervate the smooth muscle of thesmooth muscle of the
gutgut, causing, causing decreased motilitydecreased motility, and the, and the smooth muscle ofsmooth muscle of
the respiratory tractthe respiratory tract, causing, causing bronchial relaxationbronchial relaxation andand
decreased bronchial secretionsdecreased bronchial secretions..
 Sympathetic stimulationSympathetic stimulation affects theaffects the liverliver,, stimulatesstimulates
secretions of thesecretions of the sweat glandssweat glands, and is responsible for, and is responsible for
ejaculation during male orgasmejaculation during male orgasm..
 Parasympathetic fibersParasympathetic fibers innervate theinnervate the heartheart,, slowing theslowing the
heart rateheart rate, and the, and the gutgut, causing, causing increased motilityincreased motility..
 Parasympathetic nervesParasympathetic nerves innervateinnervate bronchial smoothbronchial smooth
musclemuscle, causing, causing airway constrictionairway constriction, and the, and the genitourinarygenitourinary
tracttract, causing, causing erection in the maleerection in the male..

17. The Autonomic Nervous System
Structure Sympathetic Stimulation Parasympathetic Stimulation
Iris (eye muscle) Pupil dilation Pupil constriction
Salivary Glands Saliva production reduced Saliva production increased
Oral/Nasal Mucosa Mucus production reduced Mucus production increased
Heart Heart rate and force increased Heart rate and force decreased
Lung Bronchial muscle relaxed Bronchial muscle contracted
Stomach Peristalsis reduced Gastric juice secreted; motility
increased
Small Intestine Motility reduced Digestion increased
Large Intestine Motility reduced Secretions and motility increased
Liver Increased conversion of glycogen
to glucose
---
Kidney Decreased urine secretion Increased urine secretion
Adrenal medulla Norepinephrine and epinephrine
secreted
---
Bladder Wall relaxed Sphincter closed Wall contracted Sphincter relaxed

18. THE SOMATOSENSORY SYSTEMTHE SOMATOSENSORY SYSTEM
■■ The somatosensory system relays information to theThe somatosensory system relays information to the
CNS about four major body sensations:CNS about four major body sensations:
touch,touch,
temperature,temperature,
pain,pain,
body positionbody position..
Stimulation of receptorsStimulation of receptors on regions of the body wall ison regions of the body wall is
required torequired to initiate the sensory response.initiate the sensory response.
■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with each
segment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthat
sequentially relays the sensory information tosequentially relays the sensory information to thethe
spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex..
■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thethe
CNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in the
medulla and relays touch and body position. Themedulla and relays touch and body position. The
anterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andand
relays temperature and pain sensation fromrelays temperature and pain sensation from thethe
opposite side of the body.opposite side of the body.

19. The Sensory Unit
 The somatosensory experience arises from
information provided by a variety of receptors
distributed throughout the body.
 There are four major modalities of sensory
experience:
 (1) discriminative touch, which is required to
identify the size and shape of objects and their
movement across the skin;
 (2) temperature sensation;
 (3) sense of movement of the limbs and joints
of the body;
 (4) nociception or pain sense.

20. Kinds of SensitivityKinds of Sensitivity
1.1. PainfulPainful
2.2. TemperatureTemperature
3.3. TactileTactile
4.4. ProprioceptiveProprioceptive

21. DEFINITION OF PAINDEFINITION OF PAIN
 PAINPAIN –– it is typical pathological processit is typical pathological process,,
whichwhich was generated during evolutionwas generated during evolution andand
which arise owing to action on an organismwhich arise owing to action on an organism
painfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakening
ofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem
 PainPain is an “unpleasant sensory andis an “unpleasant sensory and
emotional experience associatedemotional experience associated withwith
potential tissue damage, or described inpotential tissue damage, or described in
terms ofterms of such damage.”such damage.”

22. CLASSIFICATION OF
PAIN
• Physiological pain
• Pathological pain
• Acute pain
• Chronical pain
MEDIATORS OFMEDIATORS OF
PAINPAIN• Substanse Р
• Glutamic acid
• Cholecystokinin
• Neurotensin

23. TYPES OF PAINTYPES OF PAIN
 Pain can be classified according to
 location,
 site of referral, and
 duration.
 Cutaneous pain is a sharp, burning pain that has its
origin in the skin or subcutaneous tissues.
 Deep pain is a more diffuse and throbbing pain that
originates in structures such as the muscles, bones,
and tendons and radiates to the surrounding
tissues.
 Visceral pain is a diffuse and poorly defined pain
that results from stretching, distention, or ischemia
of tissues in a body organ.
 Referred pain is pain that originates at a visceral site
but is perceived as originating in part of the body
wall that is innervated by neurons entering the same
segment of the nervous system.
 Acute pain usually results from tissue damage and
is characterized by autonomic nervous system
responses.
 Chronic pain is persistent pain that is accompanied
by loss of appetite, sleep disturbances, depression,

24. PAIN SENSATION
■ Pain is both a protective and an unpleasant physical and emotionally
disturbing sensation originating in pain receptors that respond to a
number of stimuli that threaten tissue integrity.
■ There are two pathways for pain transmission:
• The fast pathway for sharply discriminated pain that moves directly
from the receptor to the spinal cord using myelinated Aδ fibers and from
the spinal cord to the thalamus using the neospinothalamic tract
• The slow pathway for continuously conducted pain that is transmitted
to the spinal cord using unmyelinated C fibers and from the spinal cord
to the thalamus using the more circuitous and slower-conducting
paleospinothalamic tract.
■ The central processing of pain information includes transmission to the
somatosensory cortex, where pain information is perceived and
interpreted; the limbic system, where the emotional components of pain
are experienced; and to brain stem centers, where autonomic nervous
system responses are recruited.
■ Modulation of the pain experience occurs by way of the endogenous
analgesic center in the midbrain, the pontine noradrenergic neurons,
and the nucleus raphe magnus in the medulla, which sends inhibitory
signals to dorsal horn neurons in the spinal cord.

25. Classical and non-Classical and non-
classical views of painclassical views of pain
transmission and paintransmission and pain
modulationmodulation (a).(a).
Classical painClassical pain
transmissiontransmission
pathwaypathway..
(b):(b): Normal painNormal pain..
Under basalUnder basal
conditions, pain is notconditions, pain is not
modulated by glia.modulated by glia.
(c)(c) Pain facilitation:Pain facilitation:
classical view. Inclassical view. In
response to intenseresponse to intense
and/or prolongedand/or prolonged
barrages of incomingbarrages of incoming
“pain” signals, the“pain” signals, the
PTNs becomePTNs become
sensitized and over-sensitized and over-
respond to subsequentrespond to subsequent
incoming signalsincoming signals
(d)(d) PainPain
facilitation:facilitation: newnew
view. Here, glialview. Here, glial
activation isactivation is
conceptualized as aconceptualized as a
driving force fordriving force for
creating andcreating and
maintaining painmaintaining pain
facilitation.facilitation.

26. Pain TheoriesPain Theories
 Traditionally, two theories have been offered to explainTraditionally, two theories have been offered to explain
thethe physiologic basis for the pain experience.physiologic basis for the pain experience.
 TheThe firstfirst,, specificityspecificity theorytheory, regards pain as a separate, regards pain as a separate
sensory modality evoked bysensory modality evoked by the activity of specificthe activity of specific
receptors that transmit information toreceptors that transmit information to pain centers orpain centers or
regions in the forebrain where pain is experienced.regions in the forebrain where pain is experienced.
 TheThe secondsecond theory includes a group of theoriestheory includes a group of theories
collectivelycollectively referred to asreferred to as pattern theorypattern theory. It proposes that. It proposes that
pain receptorspain receptors share endings or pathways with othershare endings or pathways with other
sensory modalitiessensory modalities but that different patterns of activity
(i.e., spatial or temporal) of the same neurons can be
used to signal painful and nonpainful stimuli.
 For example, light touch applied to the skin would
produce the sensation of touch through low-frequency
firing of the receptor; intense pressure would produce
pain through high-frequency firing of the same receptor.

27. Gate control theoryGate control theory
 AA modification of specificity theory, wasmodification of specificity theory, was proposedproposed
by Melzack and Wall in 1965 to meet theby Melzack and Wall in 1965 to meet the
challengeschallenges presented by the pattern theories.presented by the pattern theories.
 This theory postulated theThis theory postulated the presence of neuralpresence of neural
gating mechanisms at thegating mechanisms at the segmental spinalsegmental spinal cordcord
level to account for interactions between pain andlevel to account for interactions between pain and
othersensory modalitiesothersensory modalities..
 According to theAccording to the gate control theorygate control theory, the, the
internuncialinternuncial neuronsneurons involved in the gatinginvolved in the gating
mechanismmechanism are activatedare activated by large-diameter, faster-by large-diameter, faster-
propagating fibers that carry tactilepropagating fibers that carry tactile informationinformation. The. The
simultaneous firing of the large-diametersimultaneous firing of the large-diameter touchtouch
fibersfibers has thehas the potential for blocking thepotential for blocking the
transmission oftransmission of impulsesimpulses from thefrom the small-diametersmall-diameter
myelinated and unmyelinatedmyelinated and unmyelinated pain fiberspain fibers..

28. NNeuromatrixeuromatrix TTheoryheory
 More recently, Melzack has developed the neuromatrix theory to
address further the brain’s role in pain as well as the multiple
dimensions and determinants of pain. This theory is particularly useful
in understanding chronic pain and phantom limb pain, in which
there is not a simple one-to-one relationship between tissue injury and
pain experience.
 The neuromatrix theory proposes that the brain contains a widely
distributed neural network, called the body-self neuromatrix, that
contains somatosensory, limbic, and thalamocortical componentssomatosensory, limbic, and thalamocortical components.
 Genetic and sensory influences determine the synaptic
architecture of an individual’s neuromatrix that integrates multiple
sources of input and evokes the sensory, affective, and cognitive
dimensions of pain experience and behavior.
 These multiple input sources include:
 somatosensory;
 other sensory impulses affecting interpretation of the situation;
 inputs from the brain addressing such things as attention, expectation,
culture, and personality;
 intrinsic neural inhibitory modulation;
 various components of stress-regulation systems.

29. PAIN
• Damage to these pathways produces a deficit
in pain and temperature discrimination and
may also produce abnormal painful
sensations (dysesthesias) usually in the
area of sensory loss. Such pain is termed
neuropathic pain and often has a strange
burning, tingling, or electric shocklike quality.
It may arise from several mechanisms.
• Damaged peripheral nerve fibers become
highly mechanosensitive and may fire
spontaneously without known stimulation.
They also develop sensitivity to
norepinephrine released from sympathetic
postganglionic neurons.
• Electrical impulses may spread abnormally
from one fiber to another (ephaptic
conduction), enhancing the spontaneous
firing of multiple fibers.
• Neuropeptides released by injured nerves
may recruit an inflammatory reaction that
stimulates pain. In the dorsal horn,
denervated spinal neurons may become
spontaneously active.
• In the brain and spinal cord, synaptic
reorganization occurs in response to injury
and may lower the threshold for pain. In
addition, inhibition of pathways that modulate
transmission of sensory information in the
spinal cord and brainstem may promote
neuropathic pain.

30. PainPain
 Free nerve endingsFree nerve endings of unmyelinatedof unmyelinated
C fibers and small-diameter myelinatedC fibers and small-diameter myelinated
AAδδ fibers in the skin convey sensoryfibers in the skin convey sensory
information in response toinformation in response to chemical,chemical,
thermal, and mechanical stimulithermal, and mechanical stimuli..
 Intense stimulationIntense stimulation of these nerveof these nerve
endingsendings evokes the sensation of painevokes the sensation of pain..
 In contrast to skin, most deep tissuesIn contrast to skin, most deep tissues
are relatively insensitive to chemical orare relatively insensitive to chemical or
noxious stimuli.noxious stimuli.
 However, inflammatory conditions canHowever, inflammatory conditions can
sensitize sensory afferents from deepsensitize sensory afferents from deep
tissues to evoke pain on mechanicaltissues to evoke pain on mechanical
stimulation. This sensitization appearsstimulation. This sensitization appears
to beto be mediated bymediated by bradykinin,bradykinin,
prostaglandins, and leukotrienesprostaglandins, and leukotrienes
released during the inflammatoryreleased during the inflammatory
response.response.
 Information fromInformation from primary afferent fibersprimary afferent fibers
is relayedis relayed via sensory gangliavia sensory ganglia to theto the
dorsal horn of the spinal corddorsal horn of the spinal cord and thenand then
to theto the contralateral spinothalamic tractcontralateral spinothalamic tract,,
which connects towhich connects to thalamic neuronsthalamic neurons
that project to thethat project to the somatosensorysomatosensory
cortexcortex..

31. Primary pain pathways
NociceptiveNociceptive
stimulistimuli
Somesthetic association cortexSomesthetic association cortex
(perception and meaning)(perception and meaning)
Limbic cortexLimbic cortex
(emotional experience)(emotional experience)
PontinePontine
noradrenergic neuronsnoradrenergic neurons
Primary somesthetic cortexPrimary somesthetic cortex
(discrimination: location and intensity)(discrimination: location and intensity)
Medullary raphe nucleusMedullary raphe nucleus
Thalamus (sensation)Thalamus (sensation)
Somesthetic nucleiSomesthetic nuclei
Spinal cord and dorsal hornSpinal cord and dorsal horn
pain modulating circuitspain modulating circuits
Periaqueductal gray (PAG)Periaqueductal gray (PAG)
(endogenous analgesic center)(endogenous analgesic center)
Medullary NRMMedullary NRM
NeospinothalamictractNeospinothalamictract
(sharp,brightpain)(sharp,brightpain)
PaleospinothalamictractPaleospinothalamictract
(dull,achingpain)(dull,achingpain)
Primary touch fibers
A-delta
(fast)
C-fiber
(slow)

32. Characteristics ofCharacteristics of
Acute and Chronic PainAcute and Chronic Pain
Characteristic Acute Pain Chronic Pain
Onset Recent Continuous or intermittent
Duration Short duration (<6 months) 6 months or more
Autonomic responses
Consistent with sympathetic fight-
orflight response*
Increased heart rate
Increased stroke volume
Increased blood pressure
Increased pupillary dilation
Increased muscle tension
Decreased gut motility
Decreased salivary flow (dry mouth)
Absence of autonomic
responses
Psychological
component
Associated anxiety
Increased irritability
Associated depression
Somatic preoccupation
Withdrawal from outside
interests
Decreased strength of
relationships
Other types of
response
Decreased sleep
Decreased libido
Appetite changes

33. Pain Threshold and Tolerance
Cando Baseline Dolorimeter
 Pain threshold and tolerance affect an
individual’s response to a painful stimulus.
Although the terms often are used
interchangeably, pain threshold and pain
tolerance have distinct meanings. Pain
threshold is closely associated with tissue
damage and the point at which a stimulus is
perceived as painful.
 Pain tolerance relates more to the total pain
experience; it is defined as the maximum
intensity or duration of pain that a person is
willing to endure before the person wants
something done about the pain.
Psychological, familial, cultural, and
environmental factors significantly influence
the amount of pain a person is willing to
tolerate. The threshold to pain is fairly uniform
from one person to another, whereas pain
tolerance is extremely variable. Separation
and identification of the role of each of
these two aspects of pain continue to pose
fundamental problems for the pain
management team and for pain researchers.

34. Alterations in Pain Sensitivity
 Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e.,
hyperalgesia)
 Primary hyperalgesia occurs at the site of injury.
 Secondary hyperalgesia occurs in nearby uninjured tissue.
 Hyperpathia is a syndrome in which the sensory threshold is raised,
but when it is reached, continued stimulation, especially if repetitive,
results in a prolonged and unpleasant experience. This pain can be
explosive and radiates through a peripheral nerve distribution. It is
associated with pathologic changes in peripheral nerves, such as
localized ischemia.
 Spontaneous, unpleasant sensations called paresthesias occur with
more severe irritation (e.g., the pins-and-needles sensation that
follows temporary compression of a peripheral nerve).
 The general term dysesthesia is given to distortions (usually
unpleasant) of somesthetic sensation that typically accompany partial
loss of sensory innervation.

35. Alterations in Pain Sensitivity
• Severe pathologic processes can result in reduced or lost
tactile (e.g., hypoesthesia, anesthesia), temperature (e.g.,
hypothermia, athermia), and pain sensation (i.e.,
hypalgesia).
• Analgesia is the absence of pain on noxious stimulation or
the relief of pain without loss of consciousness. The inability to
sense pain may result in trauma, infection, and even loss of a
body part or parts. Inherited insensitivity to pain may take the
form of congenital indifference or congenital insensitivity to
pain.
• Allodynia (Greek allo, “other,” and odynia, “painful”) is the
term used for the puzzling phenomenon of pain that follows a
non-noxious stimulus to apparently normal skin. This term is
intended to refer to instances in which otherwise normal
tissues may be abnormally innervated or may be referral sites
for other loci that give rise to pain with non-noxious stimuli.
• Trigger points are highly localized points on the skin or
mucous membrane that can produce immediate intense pain
at that site or elsewhere when stimulated by light tactile
stimulation.

36. CHRONICAL PAINFUL
SYNDROMES
Phantom pain
Causalgia
Neuralgia
Eccentric pain
Projectional pain

38. NeuralgiaNeuralgia
 NeuralgiaNeuralgia is characterized by severe, brief,is characterized by severe, brief,
often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like or
throbbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofof
a spinal or cranial nerve and usually isa spinal or cranial nerve and usually is
precipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneous
region supplied by that nerve.region supplied by that nerve.
 Trigeminal Neuralgia.Trigeminal Neuralgia.
Trigeminal neuralgia, orTrigeminal neuralgia, or tictic
douloureuxdouloureux,, is one of theis one of the
most common and severemost common and severe
neuralgias. It is manifestedneuralgias. It is manifested
byby facial ticsfacial tics oror grimacesgrimaces
and characterized byand characterized by
stabbing,stabbing, paroxysmalparoxysmal
attacks of pain that usuallyattacks of pain that usually
are limited to the unilateralare limited to the unilateral
sensory distribution of onesensory distribution of one
or more branches of theor more branches of the
trigeminal nerve, mosttrigeminal nerve, most
often the maxillary oroften the maxillary or
mandibular divisions.mandibular divisions.

39. Postherpetic Neuralgia.Postherpetic Neuralgia.
Postherpetic pain is painPostherpetic pain is pain
that persiststhat persists as aas a
complication of herpescomplication of herpes
zoster or shingles. Itzoster or shingles. It
describes thedescribes the presence ofpresence of
pain more than 1 monthpain more than 1 month
after the onset of theafter the onset of the
acuteacute attack.attack.
Postherpetic neuralgiaPostherpetic neuralgia
develops in from 10% todevelops in from 10% to
70% of70% of patients withpatients with
shingles; the riskshingles; the risk
increases with age.increases with age.
The pain ofThe pain of postherpeticpostherpetic
neuralgia occurs in theneuralgia occurs in the
areas of innervation ofareas of innervation of
thethe infected gangliainfected ganglia..
During the acute attack ofDuring the acute attack of
herpes zosterherpes zoster, the, the
reactivated virus travelsreactivated virus travels
from the ganglia to thefrom the ganglia to the
skin of the correspondingskin of the corresponding
dermatomes, causingdermatomes, causing
localized vesicularlocalized vesicular
eruptioneruption and hyperpathiaand hyperpathia
((i.e.i.e., abnormally, abnormally
exaggerated subjectiveexaggerated subjective
responseresponse to pain).to pain).

40. Postherpetic Neuralgia

41. Phantom Limb Pain
• Phantom limb pain, a type of
neurologic pain, follows
amputation of a limb or part of a
limb. As many as 70% of those
who under amputation
experience phantom pain.
• The pain often begins as
sensations of tingling, heat and
cold, or heaviness, followed by
burning, cramping, or shooting
pain. It may disappear
spontaneously or persist for
many years. One of the more
troublesome aspects of phantom
pain is that the person may
experience painful sensations
that were present before the
amputation, such as that of a
painful ulcer or bunion.

42. • Several theories have been proposed as to the causes of phantom pain.
• One theory is that the end of a regenerating nerve becomes trapped in the scar
tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar
tissue that forms becomes a barrier to regenerating outgrowth of the axon. The
growing axon often becomes trapped in the scar tissue, forming a tangled growth
(i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents and
sympathetic efferents. It has been proposed that these afferents show increased
sensitivity to innocuous mechanical stimuli and to sympathetic activity and circulating
catecholamines.
• A related theory moves the source of phantom limb pain to the spinal cord,
suggesting that the pain is caused by the spontaneous firing of spinal cord neurons
that have lost their normal sensory input from the body. In this case, a closed
self-exciting neuronal loop in the posterior horn of the spinal cord is postulated to
send impulses to the brain, resulting in pain. Even the slightest irritation to the
amputated limb area can initiate this cycle.
• Other theories propose that the phantom limb pain may arise in the brain. In one
hypothesis, the pain is caused by changes in the flow of signals through
somatosensory areas of the brain.
• Treatment of
phantom limb pain
has been
accomplished by the
use of sympathetic
blocks, TENS of the
large myelinated
afferents innervating
the area, hypnosis,
and relaxation
training.

43. Antinociceptive systemsAntinociceptive systems
 NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin
 NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,,
dopaminedopamine
 HormonalHormonal opiate systemopiate system –– hormoneshormones ofof
adenohypophysisadenohypophysis
 HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin

44. Hormonal unopiate systemHormonal unopiate system
 1.1. Adrenocorticotropic hormoneAdrenocorticotropic hormone
 2.2. MelanostimulatingMelanostimulating hormoneshormones
 3.3. ββ --LipotropicLipotropic hormonehormone
 4.4. LargeLarge endorphinesendorphines::
kitorphinkitorphin
ββ--kosomorphinkosomorphin
dinorphindinorphin

45. 1.1. Opening of abscessOpening of abscess
2.2. Reposition ofReposition of
fragmentsfragments
3.3. Splintation of extremitySplintation of extremity
4.4. Section of scarsSection of scars
5.5. DesympathizationDesympathization
1.1. AcupunctureAcupuncture
2.2. ElectroacupunctureElectroacupuncture
3.3. LaseropunctureLaseropuncture
4.4. ElectrostimulationElectrostimulation
5.5. ElectrophoresisElectrophoresis
6.6. UltrasoundUltrasound
7.7. Magnetico-laserMagnetico-laser therapytherapy
8.8. MassageMassage
9.9. ManualManual therapytherapy
METHODS OFMETHODS OF
ANAESTIZATIONANAESTIZATION
 PsycologicalPsycological
 PhysicalPhysical
 PharmacologicalPharmacological
 SurgicalSurgical
 NeurosurgicalNeurosurgical
1.1. ConversationConversation
2.2. RelaxationRelaxation
3.3. HypnosisHypnosis
4.4. AutotrainingAutotraining
5.5. CorrectCorrect stereotypestereotype of motionof motion
6.6. Self-removel of painSelf-removel of pain

46. Upper Motor NeuronsUpper Motor Neurons
 Planned movements and those guided by sensory,
visual, or auditory stimuli are preceded by
discharges from prefrontal, somatosensory, visual,
or auditory cortices, which are then followed by
motor cortex pyramidal cell discharges that occur
several milliseconds before the onset of movement
 AnatomyAnatomy
 TheThe motor cortexmotor cortex is theis the
region from whichregion from which
movements can be elicitedmovements can be elicited
by electrical stimuli (Figure).by electrical stimuli (Figure).
 This includes:
 the primary motor area
(Brodmann area 4),
 premotor cortex (area 6),
 supplementary motor
cortex (medial portions of
6),
 primary sensory cortex
(areas 3, 1, and 2).
 In the motor cortex, groups
of neurons are organized in
vertical columns, and
discrete groups control
contraction of individual
muscles.

47. ► Cortical motor neuronsCortical motor neurons contribute axons thatcontribute axons that
converge in the corona radiata and descend in theconverge in the corona radiata and descend in the
posterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebral
peduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibers
constitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbar
tractstracts and together areand together are known asknown as upper motorupper motor
neuron fibersneuron fibers. As they descend through the. As they descend through the
diencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate to
innervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motor
nuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receive
input from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbar
fibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facial
muscles receive primarily crossed fibers.muscles receive primarily crossed fibers.
► In the ventral medullaIn the ventral medulla, the remaining corticospinal, the remaining corticospinal
fibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape in
cross section—thus, the namecross section—thus, the name pyramidal tractpyramidal tract.. AtAt
thethe lower end of the medullalower end of the medulla, most fibers, most fibers
decussate, although the proportion of crossed anddecussate, although the proportion of crossed and
uncrossed fibers varies somewhat betweenuncrossed fibers varies somewhat between
individuals. The bulk of these fibers descend as theindividuals. The bulk of these fibers descend as the
lateral corticospinal tractlateral corticospinal tract of the spinal cord.of the spinal cord.
► Different groups ofDifferent groups of neurons in the cortex controlneurons in the cortex control
muscle groupsmuscle groups of the contralateral face, arm, andof the contralateral face, arm, and
legleg. Neurons near the ventral end of the central. Neurons near the ventral end of the central
sulcus control muscles of the face, whereassulcus control muscles of the face, whereas
neurons on the medial surface of the hemisphereneurons on the medial surface of the hemisphere
control leg muscles. Because thecontrol leg muscles. Because the movements of themovements of the
face, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, a
large share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to their
controlcontrol. A. A somatotopic organizationsomatotopic organization is also apparentis also apparent
in thein the lateral corticospinal tractlateral corticospinal tract of the cervicalof the cervical
cord, where fibers to motor neurons that control legcord, where fibers to motor neurons that control leg
muscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motor
neurons lie medially.neurons lie medially.

48. Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
Amyotrophic lateral sclerosis (ALS), fatal combined degeneration of
motoneurons and motor fiber tracts (i.e. combined gray and white matter disease).
Motoneurons of entire neuraxis! ALS - most devastating neurodegenerative
disease of aging CNS that so resembles Alzheimer and Parkinson diseases.

49. Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
• Amyotrophic lateral sclerosis (ALS), also known as Lou
Gehrig’s disease after the famous New York Yankees
baseball player, is a devastating neurologic disorder that
selectively affects motor function. ALS is primarily a disorder
of middle to late adulthood, affecting persons between 55
and 60 years of age, with men developing the disease nearly
twice as often as women.
ETIOPATHOPHYSIOLOGY, PATHOLOGY
• Neuron degeneration, atrophy, and loss → glial replacement.
No inflammation! Degeneration of motoneurons:
• 1. Motor cortex (pyramidal cells in precentral cortex) → loss
of large myelinated fibers in anterior & lateral spinal
columns (gliotic sclerosis of lateral columns = LATERAL
SCLEROSIS)
N.B. posterior columns are usually spared in SALS.N.B. posterior columns are usually spared in SALS.
• 2. Brain stem - lower nuclei are more often / more
extensively involved than upper nuclei (e.g. oculomotor
nuclei loss is modest and rarely demonstrable clinically,
whereas hypoglossal nuclei are prominently degenerated).
• 3. Spinal anterior horns → loss of myelinated fibers in
anterior root →muscle denervation atrophy
(AMYOTROPHY); reinnervation is possible (but much less
extensive as in poliomyelitis, peripheral neuropathy).

50. Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Cytoplasmic ultrastructural abnormalities (cytoskeleton is affectedCytoplasmic ultrastructural abnormalities (cytoskeleton is affected
early!):early!):
1) in proximal motor axons - strongly argentophilic1) in proximal motor axons - strongly argentophilic SPHEROIDSSPHEROIDS
(accumulated(accumulated neurofilament bundlesneurofilament bundles that may contain other cytoplasmicthat may contain other cytoplasmic
structures, such as mitochondria).structures, such as mitochondria).
some patients have mutations insome patients have mutations in neurofilament heavy chain subunitneurofilament heavy chain subunit
(22q).(22q).
abnormal neurofilaments interfere with axonal transport, resulting inabnormal neurofilaments interfere with axonal transport, resulting in
failure to maintain axonal structure and transport of macromoleculesfailure to maintain axonal structure and transport of macromolecules
such as neurotrophic factors required for motor neuron survival.such as neurotrophic factors required for motor neuron survival.
2)2) Bunina bodiesBunina bodies - tiny round eosinophilic structures.- tiny round eosinophilic structures.
3)3) Lewy body-like eosinophilic inclusionsLewy body-like eosinophilic inclusions (immunoreactive to(immunoreactive to
neurofilaments, ubiquitinneurofilaments, ubiquitin ((marker for degenerationmarker for degeneration)), and gene encoding, and gene encoding
Cu/Zn superoxide dismutase [SOD1]).Cu/Zn superoxide dismutase [SOD1]).
Number of abnormalities inNumber of abnormalities in GLUTAMATEGLUTAMATE metabolism have beenmetabolism have been
identified in ALS (incl. alterations in tissue glutamate levels, transporteridentified in ALS (incl. alterations in tissue glutamate levels, transporter
proteins, postsynaptic receptors) - primary or secondary events?proteins, postsynaptic receptors) - primary or secondary events?
60% patients have60% patients have large decrease in GLUTAMATE TRANSPORTlarge decrease in GLUTAMATE TRANSPORT
activity*activity* in motor cortex and spinal cord (but not in other regions ofin motor cortex and spinal cord (but not in other regions of
central nervous system) → ↑ extracellular levels of glutamate →central nervous system) → ↑ extracellular levels of glutamate →
excitotoxicity.excitotoxicity.
*loss of astrocytic*loss of astrocytic glutamate transporter protein EAAT2glutamate transporter protein EAAT2 (due to defect in(due to defect in
mRNA splicing).mRNA splicing).

51. DemyelinationDemyelination
 InIn myelinated nervesmyelinated nerves, the axon between two nodes of Ranvier (internodal, the axon between two nodes of Ranvier (internodal
segment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition for
saltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagation
of excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). The
internodal segment itself cannot generate an action potential, i.e.,internodal segment itself cannot generate an action potential, i.e.,
depolarization of the second node (R2) is completely dependent on thedepolarization of the second node (R2) is completely dependent on the
current from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strong
that it can even jump across the nodes.that it can even jump across the nodes.
 Nevertheless, on the way along the internodal segment the amplitude of theNevertheless, on the way along the internodal segment the amplitude of the
current will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segment
must change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust be
discharged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can also
escape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orange
arrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes the
membrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of the
membrane condensor to be reduced.membrane condensor to be reduced.
 TheThe resistanceresistance of the axonal membrane of the internodal segment is veryof the axonal membrane of the internodal segment is very
high because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, the
perimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the free
extracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to the
large distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellular
space as well as the low polarity of the fatty material in the space betweenspace as well as the low polarity of the fatty material in the space between
them.them.

53. DemyelinationDemyelination can becan be
caused by degenerative,caused by degenerative,
toxic, or inflammatorytoxic, or inflammatory
damage to the nerves,damage to the nerves,
or by a deficiency ofor by a deficiency of
vitamins B6 or B12.vitamins B6 or B12.
If this happens, Rm willIf this happens, Rm will
be reduced and Cmbe reduced and Cm
raised in the internodalraised in the internodal
segment.segment.
As a result, more currentAs a result, more current
will be required towill be required to
change the polarity ofchange the polarity of
the internodal segmentthe internodal segment
and, through opening upand, through opening up
the ionic channels, largethe ionic channels, large
losses of current maylosses of current may
occur.occur.

54. Multiple SclerosisMultiple Sclerosis
• Multiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause of
neurologic disability among young and middleaged adults. Approximately two thirds
of persons with MS experience their first symptoms between 20 and 40 years of age.
In approximately 80% of the cases, the disease is characterized by exacerbations
and remissions over many years in several different sites in the CNS.
• Initially, there is normal or nearnormal neurologic function between exacerbations. As
the disease progresses, there is less improvement between exacerbations and
increasing neurologic dysfunction.

55. Huntington's diseaseHuntington's disease
 Huntington's diseaseHuntington's disease is inherited as anis inherited as an
autosomal dominant disorder.autosomal dominant disorder.
 When disease onset occurs later in life,When disease onset occurs later in life,
patients develop involuntary, rapid, jerkypatients develop involuntary, rapid, jerky
movements (movements (choreachorea) and slow writhing) and slow writhing
movements of the proximal limbs and trunkmovements of the proximal limbs and trunk
((athetosisathetosis).).
 When disease onset occurs earlier in life,When disease onset occurs earlier in life,
patients develop signs of parkinsonism withpatients develop signs of parkinsonism with
tremor (cogwheeling) and stiffness. Thetremor (cogwheeling) and stiffness. The
spinyspiny GABAergic neuronsGABAergic neurons of the striatumof the striatum
preferentially degenerate, resulting in a netpreferentially degenerate, resulting in a net
decrease in GABAergic output from thedecrease in GABAergic output from the
striatum. This contributes to thestriatum. This contributes to the
development of chorea and athetosis.development of chorea and athetosis.
 DopamineDopamine antagonists, which blockantagonists, which block
inhibition of remaining striatal neurons byinhibition of remaining striatal neurons by
dopaminergic striatal fibers, reduce thedopaminergic striatal fibers, reduce the
involuntary movements. Neurons in deepinvoluntary movements. Neurons in deep
layers of the cerebral cortex alsolayers of the cerebral cortex also
degenerate early in the disease, and laterdegenerate early in the disease, and later
this extends to other brain regions, includingthis extends to other brain regions, including
the hippocampus and hypothalamus.the hippocampus and hypothalamus.
 Thus, the disease is characterized byThus, the disease is characterized by
cognitive defects and psychiatriccognitive defects and psychiatric
disturbances in addition to the movementdisturbances in addition to the movement
disorder.disorder.

56. HUNTINGTON DISEASEHUNTINGTON DISEASE
Classical familial,Classical familial,
genetic diseasegenetic disease
ProgressiveProgressive
motor loss andmotor loss and
dementiadementia
““chorea”, i.e.chorea”, i.e.
“jerky”“jerky”
movementsmovements
Progressive, fatalProgressive, fatal
Atrophy of basalAtrophy of basal
ganglia, i.e.,ganglia, i.e.,
corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy
Ventricular enlargementVentricular enlargement

57. CNS DEGENERATIVE DISEASESCNS DEGENERATIVE DISEASES
• SPINOCEREBELLARSPINOCEREBELLAR
DEGENERATIONSDEGENERATIONS
(ATAXIAS)(ATAXIAS)
– Spinocerebellar ataxiasSpinocerebellar ataxias
– Friedrich AtaxiaFriedrich Ataxia
– Ataxia-TelangiectasiaAtaxia-Telangiectasia

58. SPINOCEREBELLAR DEGENERATIONSSPINOCEREBELLAR DEGENERATIONS
 Cerebellar cortexCerebellar cortex
 Spinal cordSpinal cord
 Peripheral nervesPeripheral nerves
 FEATURES:FEATURES:
•ATAXIAATAXIA (loss of extremity muscle(loss of extremity muscle
coordination)coordination)
• SPASTICITYSPASTICITY
• NEUROPATHIESNEUROPATHIES

59. ACQUIREDACQUIRED
TOXIC/METABOLICTOXIC/METABOLIC
CNS DISEASESCNS DISEASES VitaminVitamin B1B1 deficiency (Wernicke-Korsakoff)deficiency (Wernicke-Korsakoff)
 VitaminVitamin B12B12 deficiency (vibratory sense)deficiency (vibratory sense)
 DiabetesDiabetes Increased/Decreased GLUCOSEIncreased/Decreased GLUCOSE
 Hepatic FailureHepatic Failure (NH4+)(NH4+)
 COCO (Cortex, hippocampus, Purkinje cells)(Cortex, hippocampus, Purkinje cells)
 CH3-OHCH3-OH, Methanol (Retinal ganglion cells), Methanol (Retinal ganglion cells)
 CH3-CH2-OHCH3-CH2-OH (acute/chronic, direct/nutrit’l)(acute/chronic, direct/nutrit’l)
 RadiationRadiation (Brain MOST resistant to Rad. Rx.)(Brain MOST resistant to Rad. Rx.)
 ChemoChemo (Methotrexate + Radiation)(Methotrexate + Radiation)

60. Discriminative SensationDiscriminative Sensation
 Primary sensory cortex providesPrimary sensory cortex provides
awareness of somatosensory informationawareness of somatosensory information
and the ability to make sensoryand the ability to make sensory
discriminations.discriminations.
 Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibration
sense are considered the primarysense are considered the primary
modalities of sensation and are relativelymodalities of sensation and are relatively
preserved in patients with damage topreserved in patients with damage to
sensory cortex or its projections from thesensory cortex or its projections from the
thalamus.thalamus.
 In contrast, complex tasks that requireIn contrast, complex tasks that require
integration of multiple somatosensoryintegration of multiple somatosensory
stimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli with
auditory or visual information are impaired.auditory or visual information are impaired.
 These include the ability to distinguishThese include the ability to distinguish twotwo
pointspoints from one when touched on the skinfrom one when touched on the skin
((two-point discriminationtwo-point discrimination), localize tactile), localize tactile
stimuli, perceive the position of body partsstimuli, perceive the position of body parts
in space, recognize letters or numbersin space, recognize letters or numbers
drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), and
identify objects by their shape, size, andidentify objects by their shape, size, and
texture (texture (stereognosisstereognosis).).

61. Anatomy of Sensory LossAnatomy of Sensory Loss
The patterns of sensory loss often indicate
the level of nervous system involvement.
Symmetric distal sensory loss in the limbs,
affecting the legs more than the arms,
usually signifies a generalized disorder of
multiple peripheral nerves
(polyneuropathy).
Sensory symptoms and deficits may be
restricted to the distribution of a single
peripheral nerve (mononeuropathy) or
two or more peripheral nerves
(mononeuropathy multiplex).
Symptoms limited to a dermatome indicate
a spinal root lesion (radiculopathy).

62. Alterations in Motor Responses andAlterations in Motor Responses and
MovementMovement
 Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absent
movements in response to painful stimuli. Brainstem reflexesmovements in response to painful stimuli. Brainstem reflexes
such as sucking and grasping responses will occur if highersuch as sucking and grasping responses will occur if higher
brain centers have been damaged.brain centers have been damaged.
 Flexion and rigidity of limbs also are motor responses indicativeFlexion and rigidity of limbs also are motor responses indicative
of brain damage.of brain damage.
 Muscle conditionsMuscle conditions that indicate abnormal brain function includethat indicate abnormal brain function include
hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),), hypokinesiahypokinesia
((decreased muscle movementsdecreased muscle movements),), paresisparesis ((muscle weaknessmuscle weakness),),
andand paralysisparalysis ((loss of motor functionloss of motor function).).
 Specific loss of cerebral cortex functioning, but no loss ofSpecific loss of cerebral cortex functioning, but no loss of
brainstem function, results in a particular body posture calledbrainstem function, results in a particular body posture called
flexor posturingflexor posturing..
 Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upper
extremities at the elbows and external rotation and extension ofextremities at the elbows and external rotation and extension of
the lower extremities. This posturethe lower extremities. This posture may be unilateral ormay be unilateral or
bilateralbilateral. Extensor posturing occurs with severe injury to higher. Extensor posturing occurs with severe injury to higher
brain centers and the brainstem and is characterized bybrain centers and the brainstem and is characterized by rigidrigid
extension of the limbs and neckextension of the limbs and neck..

63. Brown-Séquard syndrome
In the spinal cord, segregation of fiber tracts and the
somatotopic arrangement of fibers give rise to distinct
patterns of sensory loss. Loss of pain and
temperature sensation on one side of the body
and of proprioception on the opposite side occurs
with lesions that involve one half of the cord on the
side of the proprioceptive deficit (Brown-Séquard
syndrome).
Compression of the upper spinal cord causes loss of
pain, temperature, and touch sensation first in
the legs, because the leg spinothalamic fibers are
most superficial. More severe cord compression
compromises fibers from the trunk. In patients with
spinal cord compression, the lesion is often above
the highest dermatome involved in the deficit. Thus,
radiographic studies should be tailored to visualize
the cord at and above the level of the sensory deficit
detected on examination.
Intrinsic cord lesions that involve the central portions
of the cord often impair pain and temperature
sensation at the level of the lesion because the fibers
crossing the anterior commissure and entering the
spinothalamic tracts are most centrally situated.
Thus, enlargement of the central cervical canal in
syringomyelia typically causes loss of pain and
temperature sensation across the shoulders and
upper arms.

64. SPINAL CORD INJURIESSPINAL CORD INJURIES
CAUSES:CAUSES:
 TRAUMATRAUMA
 FALLSFALLS
 GSWGSW
 TUMORSTUMORS
TYPES:TYPES:
 CONCUSSIONCONCUSSION
 COMPRESSIONCOMPRESSION
 CONTUSION &CONTUSION &
TRANSECTIONTRANSECTION
 LACERATIONLACERATION
 HEMORRHAGEHEMORRHAGE
(HEMATOMYALIA)(HEMATOMYALIA)
 COMPRESSION OFCOMPRESSION OF
BLOOD SUPPLY TOBLOOD SUPPLY TO
THE CORDTHE CORD

65. Injury
Level
Segmental Sensorimotor Function Dressing, Eating Elimination Mobility
C1 Little or no sensation or control of head and
neck; no diaphragm control; requires
Continuous ventilation
Dependent Dependent Limited. Voice or sip-n-puff
controlled electric wheelchair
C2 to
C3
Head and neck sensation; some neck
control. Independent of mechanical
ventilation for short periods
Dependent Dependent Same as for C1
C4 Good head and neck sensation and motor
control; some shoulder elevation;
diaphragm movement
Dependent; may be
able to eat with
adaptive sling
Dependent Limited to voice, mouth, head,
chin, or shoulder-controlled
electric wheelchair
C5 Full head and neck control; shoulder
strength; elbow flexion
Independent with
assistance
Maximal assistance Electric or modified manual
wheel chair, needs transfer
assistance
C6 Fully innervated shoulder; wrist extension
or dorsiflexion
Independent or with
minimal assistance
Independent or with
minimal assistance
Independent in transfers and
wheelchair
C7 to
C8
Full elbow extension; wrist plantar flexion;
some finger control
Independent Independent Independent; manual
wheelchair
T1 to
T5
Full hand and finger control; use of
intercostal and thoracic muscles
Independent Independent Independent; manual
wheelchair
T6 to
T10
Abdominal muscle control, partial to good
balance with trunk muscles
Independent Independent Independent; manual
wheelchair
T11 to
L5
Hip flexors, hip abductors (L1–3); knee
extension (L2–4); knee flexion and ankle
dorsiflexion (L4–5)
Independent Independent Short distance to full
ambulation with assistance
S1 to
S5
Full leg, foot, and ankle control;
innervation of perineal muscles for
bowel, bladder, and sexual function
(S2–4)
Independent Normal to impaired
bowel and bladder
function
Ambulate independently with or
without assistance
Functional Abilities by Level of Cord InjuryFunctional Abilities by Level of Cord Injury

66. CLINICAL EFFECTS OF SCICLINICAL EFFECTS OF SCI
• SPINAL SHOCK
• REFLEX ACTIVITY
• WHIPLASH INJURY
• HERNIATED NUCLEUS PULPOSUS

68. • IMMEDIATE FLACCID PARALYSIS & SENSORY LOSS
BELOW THE LEVEL OF LESION
• PRIAPISM
• BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS
AFTER A FEW HRS
• OTHER REFLEXES REMAIN ABSENT
• 3-6 WKS
UTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES:
WEATING IS ABOLISHED
BELOW THE LEVEL OF INJURY
RINE & FECES RETAINED
ASTRIC ATONY
RTHOSTATIC HYPOTENSION
LOW, & STEADY PULSE

69. REFLEX ACTIVITY
• REPLACE SPINAL SHOCK AFTER 2-3
WEEKS IF LUMBO-SACRAL SEGMENTS
ARE UNDAMAGED
• OCCURS IN ACUTE SPINAL INJURY,
NOT IN PROGRESSIVE ONES
• AUTOMATIC BLADDER; REFLEX
SWEATING & DEFECATION
• FIRST SIGN OF WEARING OFF:
– CONTRACTION OF HAMSTRING
– FLEXION/ EXTENSION OF TOES WITH
PLANTAR STIMULATION

70. ParalysisParalysis
 ParalysisParalysis is the loss of sensory and voluntary motoris the loss of sensory and voluntary motor
function. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis is
permanent.permanent.
 ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs with
transection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is called
quadriplegiaquadriplegia..
 ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs with
transection of the cord below C6 and is calledtransection of the cord below C6 and is called
paraplegiaparaplegia..
 If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysis
may occur.may occur.
 Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord is
not transected, as a result of the destruction of thenot transected, as a result of the destruction of the
nerves following cordnerves following cord hemorrhage and swellinghemorrhage and swelling..
 In addition, demyelination of the axons in the cord canIn addition, demyelination of the axons in the cord can
lead to clinically complete lesions, even though thelead to clinically complete lesions, even though the
spinal cord may not be transected.spinal cord may not be transected.
 DemyelinationDemyelination of the axons most likely occurs as part ofof the axons most likely occurs as part of
the inflammatory response to cord injury.the inflammatory response to cord injury.

71. Clinical
Manifestations
of Paralysis
• Loss of sensation,
motor control, and
reflexes below the
level of injury, and
up to two levels
above, will occur.
Body temperature
will reflect ambient
temperature, and
blood pressure will
be reduced.
• The pulse rate is
often normal, with
low blood pressure.

72. Complications
• If damage and swelling around the cord is in the
cervical spine (down to approximately C5),
respirations may cease because of compression of
the phrenic nerve, which exits between C3 and C5
and controls the movement of the diaphragm.
• Autonomic hyper-reflexia is characterized by high
blood pressure with bradycardia (low heart rate),
and sweating and flushing of the skin on the face
and upper torso.
• In the past, individuals suffering from a C2 or higher
transection invariably died as a result of respiratory
arrest. Although this is still true for many, recent
advances in treatment modalities and better
emergency rescue service responses have resulted
in the survival of many individuals with high cord
transection.
• A severe spinal cord injury affects virtually all
systems of the body to some degree. Commonly,
urinary tract and kidney infections, skin breakdown
and the development of pressure ulcers, and muscle
atrophy occur. Depression, marital and family
stress, loss of income, and large medical expenses
are some of the psychosocial complications.

73. DysphasiaDysphasia
 Dysphasia is impairment of language comprehension or production.is impairment of language comprehension or production.
Aphasia is total loss of language comprehension or production.Aphasia is total loss of language comprehension or production.
Dysphasia usually results from cerebral hypoxia, which is oftenDysphasia usually results from cerebral hypoxia, which is often
associated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Brain
damage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebral
hemisphere.hemisphere.
 Broca's dysphasia results from damage to Broca's area in the frontalresults from damage to Broca's area in the frontal
lobe. Persons with Broca's dysphasia will understand language, butlobe. Persons with Broca's dysphasia will understand language, but
their ability to meaningfully express words in speech or writing will betheir ability to meaningfully express words in speech or writing will be
impaired. This is called expressive dysphasia.impaired. This is called expressive dysphasia.
 Wernicke's dysphasia results from damage to Wernicke's area in theresults from damage to Wernicke's area in the
left temporal lobe. With Wernicke's dysphasia, verbal expression ofleft temporal lobe. With Wernicke's dysphasia, verbal expression of
language is intact, but meaningful understanding of spoken or writtenlanguage is intact, but meaningful understanding of spoken or written
words is impaired. This is called receptive dysphasia.words is impaired. This is called receptive dysphasia.
 Agnosia is the failure to recognize an object because of the inabilityis the failure to recognize an object because of the inability
to make sense of incoming sensory stimuli. Agnosia may be visual,to make sense of incoming sensory stimuli. Agnosia may be visual,
auditory, tactile, or related to taste or smell. Agnosia develops fromauditory, tactile, or related to taste or smell. Agnosia develops from
damage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in the
cerebral cortex.cerebral cortex.

75. Alterations in Pupil Responses
• The ability of our eyes to dilate or
constrict, rapidly and equally,
depends on an intact brainstem.
• Cerebral hypoxia and many drugs
change pupil size and reactivity.
Therefore, pupil size and reactivity
offer valuable information concerning
brain integrity and function.
• Important pupil changes seen with
brain damage are pinpoint pupils
seen with opiate (heroin) overdose
and bilaterally fixed and dilated pupils
usually seen with severe hypoxia.
• Fixed pupils are typically seen with
barbiturate overdose.
• Brainstem injury presents with pupils
fixed bilaterally in the midposition.

76. DISORDERS OF THE RETINAL
BLOOD SUPPLY
■ The blood supply for the
retina is derived from
the central retinal
artery, which supplies
blood flow for the
entire inside of the
retina, and from
vessels in the choroid,
which supply the rods
and cones.
■ Central retinal occlusion
interrupts blood flow to
the inner retina and
results in unilateral
blindness.
■ The retinopathies,
which are disorders of
the retinal vessels,
interrupt blood flow to
the visual receptors,
leading to visual
impairment.
■ Retinal detachment
separates the visual
receptors from the
choroid, which
provides their major
blood supply.
Fundus of the eye
as seen in retinal
examination with an
ophthalmoscope:
(left) normal
fundus; (middle)
diabetic retinopathy
—combination of
microaneurysms,
deep hemorrhages,
and hard exudates
of background
retinopathy; (right)
hypertensive
retinopathy with
purulent exudates.
Some exudates are
scattered, while
others radiate from
the fovea to form a
macular star.

77. DISORDERS OFDISORDERS OF
THE MIDDLE EARTHE MIDDLE EAR
■ The middle ear is a small air-filled
compartment in the temporal bone.
It is separated from the outer ear
by the tympanic membrane,
contains tiny bony ossicles that aid
in the amplification and
transmission of sound to the inner
ear, and is ventilated by the
eustachian tube, which is
connected to the nasopharynx.
■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that is
continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway for
pathogens to enter thepathogens to enter the middle ear.middle ear.
■■ Otitis media (OM) refers to inflammation of the middleOtitis media (OM) refers to inflammation of the middle ear, usuallyear, usually
associated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation of
fluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachian
tube function.tube function.
■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when the
tympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear has
been replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles has
been impaired (otosclerosis).been impaired (otosclerosis).

78. HEARING LOSS
■ Hearing loss represents
impairment of the ability
to detect and perceive
sound.
■ Conductive hearing loss is
caused by disorders in
which auditory stimuli are
not transmitted through
the structures of the outer
and middle ears to the
sensory receptors in the
inner ear.
■ Sensorineural hearing
loss is caused by
disorders that affect the
inner ear, auditory nerve,
or auditory pathways.

80. Diseases of the Basal GangliaDiseases of the Basal Ganglia
 The basal ganglia areThe basal ganglia are
made up of:made up of:
 –– thethe corpus striatumcorpus striatum
(consisting of the(consisting of the caudatecaudate
nucleusnucleus and theand the
putamenputamen););
 –– the inner and outerthe inner and outer
globus pallidusglobus pallidus
(pallidum, consisting of an(pallidum, consisting of an
internal and an externalinternal and an external
part);part);
 –– thethe subthalamicsubthalamic
nucleusnucleus; and; and
 –– thethe substantia nigrasubstantia nigra
(pars reticulata [p. r.] and(pars reticulata [p. r.] and
pars compacta [p. c.]).pars compacta [p. c.]).
 TheirTheir functionfunction is mainlyis mainly
to control movement into control movement in
conjunction with theconjunction with the
cerebellum,motor cortex,cerebellum,motor cortex,
corticospinal tracts, andcorticospinal tracts, and
motor nuclei in the brainmotor nuclei in the brain
stem.stem.

81. Parkinson’s Disease Parkinson’s disease is a diseaseParkinson’s disease is a disease
of the substantia nigra (p. c.)of the substantia nigra (p. c.)
which via dopaminergic tractswhich via dopaminergic tracts
influences GABAergic cells in theinfluences GABAergic cells in the
corpus striatum. Thecorpus striatum. The causecause isis
frequently afrequently a hereditary dispositionhereditary disposition
that in middle to old age leads tothat in middle to old age leads to
degeneration of dopaminergicdegeneration of dopaminergic
neurons in the substantia nigra.neurons in the substantia nigra.
Further causes areFurther causes are traumatrauma (e.g.,(e.g.,
in boxers),in boxers), inflammationinflammation
(encephalitis),(encephalitis), impaired circulationimpaired circulation
(atherosclerosis),(atherosclerosis), tumorstumors andand
poisoningpoisoning (especially by CO,(especially by CO,
manganese, and 1-methyl-4-manganese, and 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridinephenyl-1,2,3,6-tetrahydropyridine
[MPTP], which was once used as[MPTP], which was once used as
a substitute for heroin). The cella substitute for heroin). The cell
destruction probably occurs partlydestruction probably occurs partly
by apoptosis; superoxides areby apoptosis; superoxides are
thought to play a causal role. Forthought to play a causal role. For
symptoms to occur, over 70% ofsymptoms to occur, over 70% of
neurons in the substantia nigra (p.neurons in the substantia nigra (p.
c.) must have been destroyed.c.) must have been destroyed.
 The loss of cells in the substantiaThe loss of cells in the substantia
nigra (p. c.) decreases thenigra (p. c.) decreases the
correspondingcorresponding dopaminergicdopaminergic
innervationinnervation of the striatum.of the striatum.

82. Literature:Literature:
1.1. General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:General and clinical pathophysiology / Edited by Anatoliy V. Kubyshkin – Vinnytsia:
Nova Knuha Publishers – 2011. – P.Nova Knuha Publishers – 2011. – P.627627––663838..
2.2. Russell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinicalRussell J. Greene. Pathology and Therapeutics for Pharmacists. A basis for clinical
pharmacy practice / Russell J. Greene, Norman D. Harris // Published by thepharmacy practice / Russell J. Greene, Norman D. Harris // Published by the
Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, LondonPharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London
SE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rdSE1 7JN, UK 100 South Atkinson Road, Suite 200, Greyslake, IL 60030-7820, 3rd
edition, USA. – 2008. – Chapter 7. – P. 455–512.edition, USA. – 2008. – Chapter 7. – P. 455–512.
3.3. Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &Essentials of Pathophysiology: Concepts of Altered Health States (Lippincott Williams &
Wilkins), Trade paperback (2003)Wilkins), Trade paperback (2003) // Carol Mattson Porth, Kathryn J. Gaspard. –ChaptersCarol Mattson Porth, Kathryn J. Gaspard. –Chapters
36, 38-40. – P. 637–363, 456–777.36, 38-40. – P. 637–363, 456–777.
4.4. Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing.Symeonova N.K. Pathophysiology / N.K. Symeonova // Kyiv, AUS medicine Publishing.
– 2010. – P. 512–531.– 2010. – P. 512–531.
5.5. Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //Gozhenko A.I. General and clinical pathophysiology / A.I. Gozhenko, I.P. Gurcalova //
Study guide for medical students and practitioners.Study guide for medical students and practitioners. Edited by prof. Zaporozan, OSMU. –Edited by prof. Zaporozan, OSMU. –
Odessa. – 2005. – P. 2Odessa. – 2005. – P. 29292––307307..
6.6. Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.Silbernagl S. Color Atlas of Pathophysiology / S. Silbernagl, F. Lang // Thieme.
Stuttgart. New York. – 2000. – P. 298–331.Stuttgart. New York. – 2000. – P. 298–331.
7.7. Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.Corwin Elizabeth J. Handbook of Pathophysiology / Corwin Elizabeth J. – 3th edition.
Copyright ВCopyright В.. – Lippincott Williams & Wilkins – 2008. –– Lippincott Williams & Wilkins – 2008. – Chapter 8. – P. 185–202, 208–Chapter 8. – P. 185–202, 208–
209, 220–224.209, 220–224.
8.8. Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –Robbins and Cotran Pathologic Basis of Disease 8th edition./ Kumar, Abbas, Fauto. –
2007. – Chapter2007. – Chapter 2323. – P.. – P. 881–902881–902..
9.9. Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.Copstead Lee-Ellen C. Pathophysiology / Lee-Ellen C. Copstead, Jacquelyn L.
Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123.Banasik // Elsevier Inc, 4th edition. – 2010. – P. 998–1034, 1086–1123.
10.10. Pathophysiology, Concepts of Altered Health States, Carol Mattson Porth, GlennPathophysiology, Concepts of Altered Health States, Carol Mattson Porth, Glenn
Matfin.Matfin. –– New York, Milwaukee.New York, Milwaukee. –– 2009.2009. –– P.P. 1181–12991181–1299..