PHYSIOLOGY SEMINAR
Group members:
Preeyah A/P S. Mathavan
A/L Lu Khai Xin
Sittarasu
Nyanasegara
n
Prof Dr Rebecca Wong Rafa Ibrahim Tazqia Safa Yew Xuan Xin
Rabbita
LECTURER OF
PHYSIOLOGY
1.1 What is botulinum toxin?
1.2 Which bacteria produces botulinum toxin?
Content What is the mechanism of action of the
1.3
botulinum toxin?
1.4 What are the effects of botulinum toxin on
muscle contraction?
Botulinum 1.5 What are the clinical features of botulism?
Toxin And 1.6 What is the treatment for botulism?
Its Clinical 1.7 What are some clinical applications of
botulinum toxin?
Relevance 1.8 What are the complications of
using botulinum toxin?
BTX
Widely used Botulixium Neurotoxic
in medical toxin poison
condition
Produced by
Clostridium
botulinum
PREPARED BY:PREEYAH
Botulixium Toxin is the most poisonous substances.
It is made up of Clostridium botulinum which is a bacteria
This bacteria prevents release of neurotransmitter acetylcholine from axon endings to neuromuscular junction.
Causes disease botulism.
Widely used for medical and cosmetic purpose.
There are seven main types of botulixium toxin:
• A
• B
• C1
• C2
• D
• E
• F
• G
PREPARED BY:PREEYAH
Which bacteria produces botulixium toxin?
Clostridium botulinum
Clostriduym butyricum
Clostridium baratii
The most common bacteria is Clostridium botulinum. The other two bacteria takes place
occasionally.
Anaerobic Gram positive
Characteristics of
Clostridium
botulinum
Rod shape Produces protein
PREPARED BY: PREEYAH
• Clostridium botulinum produces dangerous toxin under low oxygen conditions.
• Clostridium botulinum causes serious illness like blocking nerve functions.
• This can lead to paralysis or even death.
• Commonly found on surface of fruits, vegetable and seafood.
• Signs and symptoms of Clostridium botulinum:
• Muscle weakness
• Blurry vision
• Difficulty of breathing
• Treatment for Clostridium botulinum:
• Antitoxin should be conducted.
• Prevention of Clostridium botulinum:
• Should be sterilised and hygiene
PREPARED BY:PREEYAH
Mechanism of action
• The toxin itself is released from the bacterium as a single
chain.
• It becomes activated when cleaved by its own proteases.
• The active form consists of a two-chain protein composed of
a heavy chain polypeptide joined via disulfide bond to a light
chain polypeptide.
• The heavy chain binds to synaptotagmin (receptors).
• It is also responsible for mediating translocation of the light
chain into the host cell cytoplasm as the vacuole acidifies.
PREPARED BY: LU KHAI XIN
• The light chain is the active part of the toxin.
• It is internalized into the vesicle through endocytosis.
• Within the vesicle, the light chain is translocated into the host cell cytoplasm.
• It cleaves the synaptic brevin in the acetylcholine containing vesicles through an enzymatic process.
• In the nerve ending, this process results in the inability for the acetylcholine containing vesicles to fuse with the
host cell membrane.
• There is no releasing of neurotransmitter acetylcholine.
• As a result, chemo denervation occurs.
• In some other case, it cleaves the host protein SNAP-25 (a type of SNARE protein family, which is found on the
neuronal membrane)
• The cleaved SNAP-25 cannot mediate fusion of vesicles with the host cell membrane.
• Thus preventing the release of the neurotransmitter acetylcholine from axon endings.
• The receptors are not activated, so no action potential is generated in muscle fibers.
• The muscles are unable to contract, resulting in flaccid paralysis.
• This blockage is slowly reversed as the toxin loses activity and the SNARE proteins are slowly regenerated by
the affected cell.
PREPARED BY: LU KHAI XIN
What are the effects of botulinum toxin
on muscle contraction?
•Botulinum toxin works by inhibiting the release of acetylcholine so that muscles cannot
contract and temporary paralysis occurs. There are 2 mechanism effects that occur
PREPARED BY: TAZQIA
Muscle-Nerve
Stage I communication block
Botulinum toxin blocks the transmission of overactive nerve impulses to the
targeted muscle selectively
preventing the release of the neurotransmitter acetylcholine (ACh) at the
muscle nerve junction, preventing temporary muscle contraction. The
effects that occur are only local. In cervical dystonia, Botulinum toxin can
also prevent the release of neuropeptides due to pain stimulation in
peripheral nerves.
Restoration of
Stage II Muscular-Neural
Communication
The effects of botulinum toxin are generally temporary. Previous nerve
impulse activity and associated muscle contractions restart after
several months, depending on the individual and the indication for
treatment
PREPARED BY: TAZQIA
Foodborne botulism
Symptoms of foodborne botulism typically begin 12 to 36
hours after the toxin gets into your body. But depending on
how much toxin you consumed, the start of symptoms may
range from a few hours to a few days.
Symptoms of foodborne botulism include:
•Trouble swallowing or speaking
Clinical features of •Dry mouth
botulism •Facial weakness on both sides of the face
•Blurred or double vision
•Drooping eyelids
•Trouble breathing
•Nausea, vomiting and stomach cramps
•Paralysis
PREPARED BY: RAFA
Wound botulism
Symptoms of wound botulism appear about 10 days after the toxin enters your body. Wound botulism symptoms include:
•Trouble swallowing or speaking
•Facial weakness on both sides of the face
•Blurred or double vision
•Drooping eyelids
•Trouble breathing
•Paralysis
The area around the wound may not always appear swollen and show a change of colour.
Iatrogenic botulism
In iatrogenic botulism — when the toxin is injected for cosmetic or medical reasons — there have been rare occurrences of serious side effects. These may
include headache, facial paralysis, and muscle weakness.
PREPARED BY: RAFA
Infant botulism
• Problems generally begin 18 to 36 hours after the toxin enters the baby's body.
Symptoms include:
• Constipation, which is often the first symptom
• Floppy movements due to muscle weakness and trouble controlling the head
• Weak cry
• Irritability
• Drooling
• Drooping eyelids
• Tiredness
• Trouble sucking or feeding
• Paralysis
• Certain symptoms don't typically occur with botulism. For example, botulism doesn't usually raise blood pressure or heart rate or cause
fever or confusion. Sometimes, though, wound botulism may cause fever.
PREPARED BY: RAFA
TREATMENT
• Antitoxin
- Lower the risk of complications
- Block the bacteria’s production
- Prevent toxin cause any more harm
to the patient
• Antibiotics
- Treatment for wound botulism
- Not used for other form of botulism
- It can speed up the release of toxins
on the wound site
PREPARED BY: YEW XUAN XIN
TREATMENT
• Breathing assistance
- Toxin paralyzed the muscles involve in breathing.
- It need the help of mechanical ventilator (breathing machine)
- Ventilator force air into the lungs via tube inserted in the airway from mouth or
nose
• Rehabilitation
- Patient may need therapy to improve functions that affected by botulism.
- Eg: speech, swallowing, etc.
PREPARED BY: YEW XUAN XIN
COMPLICATIONS OF USING
BOTULINUM TOXIN
Headache Nausea Redness
Bruising and
Flu-like
pain at the Fatigue
symptoms
injection site
Temporary Muscle Breathing
drooping weakness problems
PREPARED BY: YEW XUAN XIN
Clinical Application of Botulinum Toxin
• In 1984, Andrew Blitzer first injected botulinum toxin A
• Injected into vocal cord muscle to treat laryngeal dystonia (chronic voice
disorder characterized by spasms of the muscles of the voice box )
• Only serotype A and B are used in clinical practice
• Botulinum A and B has longer period of action
• Treat disorders of muscle tone, including spasticity associated with cerebral
palsy (affect a person's ability to move and maintain balance and posture)
• Prevention of chronic migraine
• Brain trauma and stroke
• Dizziness, headache and muscle weakness are common side effects
PREPARED BY:N. MATHAVAN
Reference
• https://www.mayoclinic.org/diseases-conditions/botulism/diagnosis-treatment/drc-20370266
• https://www.mayoclinic.org/tests-procedures/botox/about/pac-20384658
• https://www.cdc.gov/botulism/testing-treatment.html#:~:text=Doctors%20treat%20botulism%20with%20a,
well%20enough%20to%20go%20home
• https://webwiser.nlm.nih.gov/substance?substanceId=437&identifier=Botulism&identifierType=name&men
uItemId=100&catId=175
• https://academic.oup.com/cid/article/66/suppl_1/S11/4780420
• Jankovic J . Dystonia: medical therapy and botulinum toxin. Adv Neurol2004;94:275–86.
• Hallet,Mark., Albanese, Alberto., Dressler, Dirk., Segal, Karen R., Simpson, David., Truong, Daniel.,
Jankovic, Joseph. Evidence-based review and assessment of botulinum. Toxicon 67 (2013) 94–114
• Nigam, P.K; Nigam, A.Botulinum toxin. Indial J Dermatol: 2010:55 (1):8-14. Available from
:http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856357/
• https://en.wikipedia.org/wiki/Botulinum_toxin
• https://www.who.int/news-room/fact-sheets/detail/botulism#:~:text=Clostridium%20botulinum%20is%20a
%20bacterium,to%20respiratory%20and%20muscular%20paralysis