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GENESIS OF TETANUS
RAIHAN MANNAN
JR-1
Deptt. of Physiology
JNMC, AMU
MYOGRAM OF A SIMPLE
TWITCH
mple twitch: Brief contraction of all fibers in a motor unit in response to
a single stimulus.
TIMING OF ELECTRICAL &
MECHANICAL EVENTS
Myogram of Single Muscle
SUMMATION
Summation means the increased in activity of
tissue produced by multiple stimulation as
compared to single stimulus
When a single response is obtained by giving two
stimuli, either simultaneously or in close
succession (one after the other), and the response
is greater than that obtained by either stimulus
alone
The tension developed during summation is
considerably greater than that during the single
muscle twitch
2 FORMS OF
SUMMATION
1)SUMMATION OF STIMULI: multiple sub-threshold
stimuli to produce muscular response
2) SUMMATION OF CONTRACTION: increase in
magnitude of contraction as a result of multiple
stimulation. 2 types
i) Temporal Summation: increase force of
contraction due to increase in frequency of
stimulation
ii) Spatial Summation: increase force of contraction
due to increase in strength of stimulus; recruitment
of motor unit
SUMMAATION OF 2
SUCCESSIVE STIMULI
Response to 2nd stimulus depends upon how
soon after the first stimulus it is given: if the
2nd stimulus…….
i) falls on the 1st half of Latent period  no
response
ii) falls on 2nd half of Latent Period  increased
response
iii) falls during Contarction Period  increased
response
iv) falls during Relaxation Period  increased
response
INCREASED RESPONSE
IS DUE TO BENEFICIAL
EFFECT
a) Release of more Ca2+ from
sarcoplasmic reticulum;
b) Increase in temp. of muscle;
c) Decrease in internal viscosity and
resistance of the muscle (series elastic
element being already stretched);
d) Decrease in inertia of the recording
system.
As the frequency increases, there comes a point
where each new contraction occurs before the
preceding one is over
As a result, the second contraction is added partially
to the first, and force of contraction rises
progressively with increasing frequency
When the frequency reaches a critical level, the
successive contractions become so rapid that they
fuse together; state of sustained contraction
When force of contraction reaches maximum  no
effect of increasing frequency of stimullus
B,coz enough Ca2+ ions are maintained so that full
contractile state is sustained without any relaxation 
GENESIS OF TETANUS
STAIRCASE
PHENOMENON (TREPPE)
When a series of stimuli is delivered to skeletal
muscle, so that each stimulus fall at the end of
realaxation phase
Increase in the tension developed during each
twitch, after several contractions, a uniform tension
per contraction is reached
This phenomenon is known as treppe, or "staircase"
phenomenon
This is the basis of “warm up”
Treppe is believed to be due to release of more &
more Ca2+ ions from SR and failure of recapture of
ions immediately
STAIRCASE
PHENOMENON (TREPPE)
STAIRCASE EFFECT,
SUMMATION AND TETANUS
CLONUS
When a series of maximal stimuli are
delivered to a skeletal muscle, so that
each stimulus fall during mid relaxation
phase of previous twitch
Muscle relaxes, but not completely
Such response is known as Clonus
TETANUS
With rapidly repeated stimulation during
contraction phase, activation of the contractile
mechanism occurs repeatedly before any
relaxation has occurred
Individual responses fuse into one continuous
contraction
Such a response is called a tetanus or tetanic
contraction
COMPLETE V/S
INCOMPLETE TETANUS
Complete tetanus when there is no relaxation
between stimuli
When a series of maximal stimulus is delivered to a
skeletal muscle so that each stimuli fall in the
contraction phase
Incomplete tetanus when there are periods of
incomplete relaxation between the summated stimuli
When a series of maximal stimulus is delivered to a
skeletal muscle so that each stimuli fall in the early
relaxation phase
Stimuli
Partial relaxation
Low stimulation frequency
unfused (incomplete) tetanus
(b) If another stimulus is applied before the muscle
relaxes completely, then more tension results.
This is temporal (or wave) summation and results
in unfused (or incomplete) tetanus.
Stimuli
High stimulation frequency
fused (complete) tetanus
(c) At higher stimulus frequencies, there is no relaxation
at all between stimuli. This is fused (complete) tetanus.
MYOGRAMS CREATED BY MULTIPLE
STIMULI
Wave Summation: Two stimuli that occur close together so that
the second
stimulus occurs before the the muscle can completely relax.
Increased force of contraction is due to recruitment of motor
units.
Unfused or Incomplete Tetanus: Due multiple stimuli that cause
MYOGRAMS CREATED BY
MULTIPLE STIMULI
Fused or Complete Tetanus: A sustained maximum contraction
in which
individual contractions are not discernable. In fused tetanus,
multiple stimuli are occurring so fast, the muscle does not
undergo any relaxation.
TETANIZING FREQUENCY: RATE OF
STIMULATION AT WHICH SUMMATION OF
CONTRACTIONS WILL OCCUR (I.E. TETANUS
WILL OCCUR)
= 1/CONTRACTION PERIOD
DURATION
FACTORS AFFECTING MINIMUM TETANIZABLE FREQUENCY:
a) Strength of stimulation: affect the contraction period
b) Fatigue of muscle: it increases the duration of CP 
lesser frequency of stimulation is required for obtaining
tetanus
c) Temperature: higher temp. decreases the duration of CP
 more frequency is required for tetanus
d) Slow and fast muscle: fast muscles have higher
tetanizing frequency
 Maintenance of physiological rate of nerve stimulation:
Renshaw cell keeps the stimulation rate maintained at
TETANUS
Contracture: reversible process; here ATP required
for Ca2+ reuptake into SR is not available 
contracted muscle fails to relax
Rigor: irreversible process; here muscle fibres are
completely depleted of ATP and Phosphocreatine 
develop state of extreme rigidity
When this occurs after death, the condition is k/a
Rigor Mortis
Heat rigor: here denaturation of protein occur 
conformational changes of muscle protein can’t
occur  muscle protein stuck into contracted state
Tetany: due to decrease in ionized Ca2+ (<50% of
normal)  increase in membrane permeability to
Na+  N-M hyperexcitability  extensive spasm of
skeletal muscle  cramps in extremities
Fatigue: temporary reduction of working capacity of
a cell, organ or organism as a whole due to
prolonged exertion; reversible phenomenon &
passes off after rest
Reason: depletion of neurotransmitters, lack of
nutrition & accumultion of waste metabolites
CARDIAC MUSCLE CAN’T BE
TETANIZED: summation of contractile
response is not possible
RELEVANCE OF THIS
EXPERIMENT TO
MEDICAL PHYSIOLOGY
Muscular activity is involved in maintenance of
posture
Physiological basis of tonic-clonic seizures can
be explained
Symptoms of Pathological Tetanus and Tetany
have much common in Physiological Tetanus
ETIOLOGY:
Tetanus is caused by Clostridium tetani
Gram positive anaerobic bacillus
One of two genera that form spores
Two forms: vegetative form and spore
form
Vegetative form: actively secretes toxin
and cause disease
Spore form: Dormant and metabolically
inert, important in disease transmission
PATHOLOGICAL TETANUS
Spores present in soil, dust,
manure, dirty metallic objects
e.g. nails, sharp rusted metallic
objects, wood pieces, etc.
Spores excreted in feces of horse,
sheep, chicken and other
animals
Soil mixed with feces-spores
remain in soil for long time
Non communicable disease
Spores (& not Vegetative form) are
important in disease transmission
Spores enter body through cuts,
lacerations, deep wounds,
puncture wound etc.
Neonatal tetanus-contaminated
equipments to cut umbilical cord
African nation-ritual of putting
animal dung on umbilical stump
TETANUS-TRANSMISSION
TETANUS-TRANSMISSION
The spore can get into the body through broken
skin -injuries from contaminated objects.
Breaks in skin more likely to get infected
•Wounds contaminated with dirt, feces, spit (saliva)
•Puncture wounds- nail, needle, thorn
•Burns
•Crush injuries
•Injuries with dead tissue
• Rare ways of transmission
 Clean superficial wounds, surgical procedures, insect/
animal bites, compound fractures, I/V drug users
TETANUS-PATHOGENESIS
Incubation Period- 3-21 days
Average IP 10 days
Spores carried deep inside wound
Anaerobic atmosphere: dead tissue,
deep in tissue, foreign body, co-
infection with aerobic organisms
Spores germinate into vegetative form
TETANUS-PATHOGENESIS
Vegetative form remain localized to wound
Secrete toxin Tetanospasmin
Active fragment binds to pre-synaptic motor neurons
Retrograde axonal transport:- to spinal cord and brain stem
Toxin diffuses to inhibitory cells: Glycinergic and GABAergic
neurons
Toxin degrades Synaptobrevin-docking protein of pre-
synaptic vesicles
TETANUS-PATHOGENESIS
Release of inhibitory
neurotransmitters Glycine & GABA
is blocked
Uninhibited spastic contraction of
muscles
Hyper-reflexia, spastic paralysis of
muscles
Lock jaw, trismus, neck stiffness,
difficulty swallowing
COMPLICATIONS:
•Laryngospasm
•Fractures
•Hospital-acquired infections
•Pulmonary embolism
•Aspiration pneumonia
•Breathing difficulty, possibly leading
to death
TETANUS PREVENTION
PRIMARY PREVENTION
A. PREGNANT LADIES
 TT between 27 & 36 weeks
B. NEWBORNS
 DPT -2,3,4 months
C. PRE-SCHOOL (3-5 years)
 DPT booster
D. ADULTS(13-18 years)
 Single TT booster
TETANUS PREVENTION
SECONDARY PREVENTION
NOT IMMUNIZED
OR INCOMPLETE
FULLY
IMMUNIZED
IMMUNIZATION
STATUS
Active immunization
with tetanus toxoid
No immunizationMinor wound
TETANUS TREATMENT
1. Wound debridement
2. Antimicrobial therapy: Metronidazole preferred over
Penicillin G
3. Penicillin G -structurally similar to GABA and
competitively antagonizes this
neurotransmitter
4. Management of clinical tetanus: Human tetanus
immunolobulin (TIG)
5. General supportive management e.g. airway
management, physiotherapy etc.
6. Spasmolytics
THANK
YOU

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Genesis of tetanus

  • 1. GENESIS OF TETANUS RAIHAN MANNAN JR-1 Deptt. of Physiology JNMC, AMU
  • 2. MYOGRAM OF A SIMPLE TWITCH mple twitch: Brief contraction of all fibers in a motor unit in response to a single stimulus.
  • 3.
  • 4.
  • 5. TIMING OF ELECTRICAL & MECHANICAL EVENTS Myogram of Single Muscle
  • 6. SUMMATION Summation means the increased in activity of tissue produced by multiple stimulation as compared to single stimulus When a single response is obtained by giving two stimuli, either simultaneously or in close succession (one after the other), and the response is greater than that obtained by either stimulus alone The tension developed during summation is considerably greater than that during the single muscle twitch
  • 7. 2 FORMS OF SUMMATION 1)SUMMATION OF STIMULI: multiple sub-threshold stimuli to produce muscular response 2) SUMMATION OF CONTRACTION: increase in magnitude of contraction as a result of multiple stimulation. 2 types i) Temporal Summation: increase force of contraction due to increase in frequency of stimulation ii) Spatial Summation: increase force of contraction due to increase in strength of stimulus; recruitment of motor unit
  • 8. SUMMAATION OF 2 SUCCESSIVE STIMULI Response to 2nd stimulus depends upon how soon after the first stimulus it is given: if the 2nd stimulus……. i) falls on the 1st half of Latent period  no response ii) falls on 2nd half of Latent Period  increased response iii) falls during Contarction Period  increased response iv) falls during Relaxation Period  increased response
  • 9. INCREASED RESPONSE IS DUE TO BENEFICIAL EFFECT a) Release of more Ca2+ from sarcoplasmic reticulum; b) Increase in temp. of muscle; c) Decrease in internal viscosity and resistance of the muscle (series elastic element being already stretched); d) Decrease in inertia of the recording system.
  • 10. As the frequency increases, there comes a point where each new contraction occurs before the preceding one is over As a result, the second contraction is added partially to the first, and force of contraction rises progressively with increasing frequency When the frequency reaches a critical level, the successive contractions become so rapid that they fuse together; state of sustained contraction When force of contraction reaches maximum  no effect of increasing frequency of stimullus B,coz enough Ca2+ ions are maintained so that full contractile state is sustained without any relaxation  GENESIS OF TETANUS
  • 11. STAIRCASE PHENOMENON (TREPPE) When a series of stimuli is delivered to skeletal muscle, so that each stimulus fall at the end of realaxation phase Increase in the tension developed during each twitch, after several contractions, a uniform tension per contraction is reached This phenomenon is known as treppe, or "staircase" phenomenon This is the basis of “warm up” Treppe is believed to be due to release of more & more Ca2+ ions from SR and failure of recapture of ions immediately
  • 14. CLONUS When a series of maximal stimuli are delivered to a skeletal muscle, so that each stimulus fall during mid relaxation phase of previous twitch Muscle relaxes, but not completely Such response is known as Clonus
  • 15. TETANUS With rapidly repeated stimulation during contraction phase, activation of the contractile mechanism occurs repeatedly before any relaxation has occurred Individual responses fuse into one continuous contraction Such a response is called a tetanus or tetanic contraction
  • 16. COMPLETE V/S INCOMPLETE TETANUS Complete tetanus when there is no relaxation between stimuli When a series of maximal stimulus is delivered to a skeletal muscle so that each stimuli fall in the contraction phase Incomplete tetanus when there are periods of incomplete relaxation between the summated stimuli When a series of maximal stimulus is delivered to a skeletal muscle so that each stimuli fall in the early relaxation phase
  • 17. Stimuli Partial relaxation Low stimulation frequency unfused (incomplete) tetanus (b) If another stimulus is applied before the muscle relaxes completely, then more tension results. This is temporal (or wave) summation and results in unfused (or incomplete) tetanus.
  • 18. Stimuli High stimulation frequency fused (complete) tetanus (c) At higher stimulus frequencies, there is no relaxation at all between stimuli. This is fused (complete) tetanus.
  • 19. MYOGRAMS CREATED BY MULTIPLE STIMULI Wave Summation: Two stimuli that occur close together so that the second stimulus occurs before the the muscle can completely relax. Increased force of contraction is due to recruitment of motor units. Unfused or Incomplete Tetanus: Due multiple stimuli that cause
  • 20. MYOGRAMS CREATED BY MULTIPLE STIMULI Fused or Complete Tetanus: A sustained maximum contraction in which individual contractions are not discernable. In fused tetanus, multiple stimuli are occurring so fast, the muscle does not undergo any relaxation.
  • 21. TETANIZING FREQUENCY: RATE OF STIMULATION AT WHICH SUMMATION OF CONTRACTIONS WILL OCCUR (I.E. TETANUS WILL OCCUR) = 1/CONTRACTION PERIOD DURATION FACTORS AFFECTING MINIMUM TETANIZABLE FREQUENCY: a) Strength of stimulation: affect the contraction period b) Fatigue of muscle: it increases the duration of CP  lesser frequency of stimulation is required for obtaining tetanus c) Temperature: higher temp. decreases the duration of CP  more frequency is required for tetanus d) Slow and fast muscle: fast muscles have higher tetanizing frequency  Maintenance of physiological rate of nerve stimulation: Renshaw cell keeps the stimulation rate maintained at
  • 23. Contracture: reversible process; here ATP required for Ca2+ reuptake into SR is not available  contracted muscle fails to relax Rigor: irreversible process; here muscle fibres are completely depleted of ATP and Phosphocreatine  develop state of extreme rigidity When this occurs after death, the condition is k/a Rigor Mortis Heat rigor: here denaturation of protein occur  conformational changes of muscle protein can’t occur  muscle protein stuck into contracted state
  • 24. Tetany: due to decrease in ionized Ca2+ (<50% of normal)  increase in membrane permeability to Na+  N-M hyperexcitability  extensive spasm of skeletal muscle  cramps in extremities Fatigue: temporary reduction of working capacity of a cell, organ or organism as a whole due to prolonged exertion; reversible phenomenon & passes off after rest Reason: depletion of neurotransmitters, lack of nutrition & accumultion of waste metabolites
  • 25. CARDIAC MUSCLE CAN’T BE TETANIZED: summation of contractile response is not possible
  • 26. RELEVANCE OF THIS EXPERIMENT TO MEDICAL PHYSIOLOGY Muscular activity is involved in maintenance of posture Physiological basis of tonic-clonic seizures can be explained Symptoms of Pathological Tetanus and Tetany have much common in Physiological Tetanus
  • 27. ETIOLOGY: Tetanus is caused by Clostridium tetani Gram positive anaerobic bacillus One of two genera that form spores Two forms: vegetative form and spore form Vegetative form: actively secretes toxin and cause disease Spore form: Dormant and metabolically inert, important in disease transmission PATHOLOGICAL TETANUS
  • 28. Spores present in soil, dust, manure, dirty metallic objects e.g. nails, sharp rusted metallic objects, wood pieces, etc. Spores excreted in feces of horse, sheep, chicken and other animals Soil mixed with feces-spores remain in soil for long time Non communicable disease
  • 29. Spores (& not Vegetative form) are important in disease transmission Spores enter body through cuts, lacerations, deep wounds, puncture wound etc. Neonatal tetanus-contaminated equipments to cut umbilical cord African nation-ritual of putting animal dung on umbilical stump TETANUS-TRANSMISSION
  • 30. TETANUS-TRANSMISSION The spore can get into the body through broken skin -injuries from contaminated objects. Breaks in skin more likely to get infected •Wounds contaminated with dirt, feces, spit (saliva) •Puncture wounds- nail, needle, thorn •Burns •Crush injuries •Injuries with dead tissue • Rare ways of transmission  Clean superficial wounds, surgical procedures, insect/ animal bites, compound fractures, I/V drug users
  • 31. TETANUS-PATHOGENESIS Incubation Period- 3-21 days Average IP 10 days Spores carried deep inside wound Anaerobic atmosphere: dead tissue, deep in tissue, foreign body, co- infection with aerobic organisms Spores germinate into vegetative form
  • 32. TETANUS-PATHOGENESIS Vegetative form remain localized to wound Secrete toxin Tetanospasmin Active fragment binds to pre-synaptic motor neurons Retrograde axonal transport:- to spinal cord and brain stem Toxin diffuses to inhibitory cells: Glycinergic and GABAergic neurons Toxin degrades Synaptobrevin-docking protein of pre- synaptic vesicles
  • 33. TETANUS-PATHOGENESIS Release of inhibitory neurotransmitters Glycine & GABA is blocked Uninhibited spastic contraction of muscles Hyper-reflexia, spastic paralysis of muscles Lock jaw, trismus, neck stiffness, difficulty swallowing
  • 35. TETANUS PREVENTION PRIMARY PREVENTION A. PREGNANT LADIES  TT between 27 & 36 weeks B. NEWBORNS  DPT -2,3,4 months C. PRE-SCHOOL (3-5 years)  DPT booster D. ADULTS(13-18 years)  Single TT booster
  • 36. TETANUS PREVENTION SECONDARY PREVENTION NOT IMMUNIZED OR INCOMPLETE FULLY IMMUNIZED IMMUNIZATION STATUS Active immunization with tetanus toxoid No immunizationMinor wound
  • 37. TETANUS TREATMENT 1. Wound debridement 2. Antimicrobial therapy: Metronidazole preferred over Penicillin G 3. Penicillin G -structurally similar to GABA and competitively antagonizes this neurotransmitter 4. Management of clinical tetanus: Human tetanus immunolobulin (TIG) 5. General supportive management e.g. airway management, physiotherapy etc. 6. Spasmolytics