Vas a repetirlo

Questions
1. Present the “Doctor’s Notes” portion of the case with a description of the following terms or
concepts:
• Diaphoresis - ​medical term used to describe excessive, abnormal sweating in relation to your
environment and activity level. It tends to affect the whole body instead of part of the body. Usually a
symptom of an underlying health conditions.
• Motor dysfunction - ​abnormality in the motor system (muscles, nerves, or center that affects
movement).
• Paresthesia - ​prickling, burning, tingling, numb, itching, or skin crawling feeling. Can be a sign of a
more serious medical problem. (Pressure on a nerve)
• Cyanotic - ​abnormal blue discoloration of skin and mucous membranes (deoxygenated hemoglobin)
• Hypoventilation - ​breathing at an abnormally slow rate, resulting in an increased amount of carbon
dioxide in the blood (hypercapnia).
• Bradycardia - ​very slow heart rate. Normal heart rate is of 60 to 100 beats per minute (at rest).
However, people with bradycardia experience heart beats less than 60 time a minute. (It could signal a
problem with the heart’s electrical system).
• Gastric lavage - ​gastric lavage is a ​gastrointestinal decontamination technique that aims to empty
the ​stomach of toxic substances by the sequential administration and aspiration of small volumes of
fluid via an orogastric tube
• Oxygen saturation - ​oxygen saturation is the fraction of oxygen-saturated hemoglobin relative to
total hemoglobin in the blood. Can be measured using a pulse oximeter (small device that clips to
your finger). Normal arterial oxygen → 75-100 mm of mercury (mmHg), 95-100%.
● Oxygen saturation (SO​2​) measures the percentage of hemoglobin binding sites in the
bloodstream occupied by oxygen. At low partial pressures of oxygen, most hemoglobin is
deoxygenated.
2. How many different elements are contained in a molecule of tetrodotoxin? What are the
names of these elements?
The chemical formula of tetrodotoxin is C11H17N3O8. There are 4 element: Carbon, Hydrogen,
Nitrogen, and Oxygen.
3. What type of chemical bonds are found in this molecule? Describe the structure of those
bonds.
In this molecule all the bonds are covalent, all of which are single bonds except for one that is a
double bond between nitrogen and carbon. 2 HO bonds, 2 OH bonds, 2 HN bonds, 1 CH2OH bond, 1
H2N bond, and the remaining oxygens and hydrogens are not bonded.
4. As mentioned in the case description, tetrodotoxin is a molecule that blocks voltage-gated
sodium ion channels. Describe the structure of a sodium ion.
Sodium cations are osmotic laxatives. Mechanism of action just like any osmotic activity. A sodium
ion has one electron in its valence shell, meaning, it is easier to lose this electron to other species. A
sodium ion is one atom of sodium without this electron in the valence shell, so the ion has a positive
charge of +1. Atom= 11 electrons, Ion= 10 electrons.
5. What is a voltage-gated sodium ion channel? What is it made of? What is its function?
● Protein embedded in the plasma membrane.
● Found in the nerve and muscle cells.
● Used in the rapid electrical signalling between these cells.
● Subunit = polypeptide chain > 180 amino acids.
○ Polypeptide chains are mainly composed of nonpolar amino acid side chains.
■ Segments coil → transmembrane domain
● Voltage-gated sodium channel → 24 transmembrane domains in the polypeptide chain

Voltage-gated sodium channels are simple protein mechanisms that are essential in the nervous
system. These channels regulate many physiological functions making the channel an ideal drug
target. They are composed of a large subunit of amino acids folded into four domains and one or few
beta subunits that exist in electrically excited cells and are very important for the generation of nerve
impulses by the initiation and propagation of action potentials. The channels close together when their
charge is very negative and becomes positive when an action potential reaches their gates. The
proteins start to shift apart creating an opening to draw sodium ions in the cell spreading the action
potential. The main function of these channels is to open, draw sodium ions in cell, and close to allow
other ions to leave the cell.
● https://www.coursehero.com/file/16008515/Case-Study-2/
6. Why do sodium ions need channels in order to move into and out of cells?
Sodium ions need ion-channels to move into and out of cells due to the fact they have a charge, either
positive or negative, meaning they are polar molecules. The polarity of these ions will not allow them
to pass freely due to the nature of the semipermeable lipid bilayer. Ions can interact with the polar
head but not with the hydrophobic tails. Furthermore, these ions are too big to pass freely across the
membrane. Last, this is just one more mechanism from cells to ensure survival by avoiding toxicity
caused by ions that pass freely.
7. Describe the process involved in the movement of ions through these channels.
Two requirements: the forces acting on the ion must allow this movement energetically, and there
must be a pathway (open channel). Ion channels open and close because of changes in the protein
arrangements, which can be modified to open or occlude the pore. Sodium channels are activated
when the action potential is depolarized

STRUCTURE OF A NEURON
Dendrites - (numerous) extensions that receive signals from other neurons
Axon - (single) extension that transmits signals to other cells
- Longer than dendrites
Axon hillock - cone-shaped region of an axon where it joins the cell body (one end)
- Where signals that travel down the axon are generated
- Axon branches on the other end
Synapse - junction where each branched end of an axon transmits information to other cells
Synaptic terminal - the part of each axon branch that forms this specialized junction
Neurotransmitters - pass information from the transmitting neuron to the receiving cell (at most
synapses)
- Transmitting neuron = presynaptic cell
- Muscle, neuron, gland cell that receives signal = postsynaptic cell
Electrical signals = basis of information transfer in the nervous system
8. When nerve cells are at rest, there is an unequal amount of positive and negative charges on
either side of a nerve cell membrane. This charge difference is called an electrical potential.
Describe this “potential” when the neuron is at rest (resting potential).
During resting membrane potential, in a neuron cell, only potassium ions are allowed to pass to and
from the cell, slowly. This causes the inside of the cell to be more negative than the outside. The
plasma membrane is selectively permeable, therefore no other ions can pass in this resting phase.
After all the K ions have moved to the other side, the neuron is balanced and in resting potential.
When the neuron cell is at rest, the charge is measured around -60 to -70 mV.
9. What is happening to the electrical potential of a neuron when it generates an action
potential? What is the function of the action potential in neurons?
Information is encoded by electrical signals. These signals are transient perturbations from the
established resting potential of the cell. There are three types of signals: receptor potentials, synaptic
potentials, and action potentials. The function of action potential is to create a brain signal. When
action potential is generated by neurons there are several changes in the electrical potential. First of all
in resting potential neurons have a negative charge. When an action potential is released the sodium
voltage gated channel opens, the neuron goes past neutral concentration to a positive one.
Depolarization. Repolarization. Hyperpolarization.
10. Describe the role of sodium ions and sodium channels in the action potential.
Initially, the voltage gated sodium channels are opened. Ions pass freely in a great quantity during the
depolarization. During repolarization the channel closes and the potassium one opens. During
hyperpolarization they stay open for a bit and then close.
11. What would happen to a neuron if it were exposed to tetrodotoxin? Be specific regarding its
effect on the ability of a neuron to communicate.
Tetrodotoxin blocks voltage-gated sodium ion channels. When these channels become blocked, the
neuron can’t balance the charges and ion concentrations. This will result in the signal not being
propagated down the nerve. The neuron will not be able to communicate/ send information. In other
words, when TTX binds to the sodium ion channel it prevents sodium from entering the cell. The lack
of sodium ions will stop the cell from depolarizing, therefore blocking the cell from starting action
potential. Without action potential there is no communication between neurons.
12. Now that you have addressed some of the basic biology of this case, explain why Dr.
Westwood experienced numbness after eating the puffer fish meal.
Tetrodotoxin inhibits the nerves ability to transmit sensory information. The loss of sensory
information would be experienced as numbness in the areas exposed to the toxin. Inhibition of sensory
information. There is no communication. Action potential can't start therefore there is no
communication and the lack of communication is presented as numbness.
13. Paralysis is a term used to describe the loss of function of muscle. If tetrodotoxin’s effect is
on neurons, why did Dr. Westwood experience paralysis?
Due to the voltage-gated sodium ion channels being blocked, the movement of sodium ions is shut
down and the propagation of action potential is stopped. The nerve cannot transmit information. This
results in the impairment of the central and peripheral nervous systems. This impairment causes
paralysis. TTX affects sodium concentrations, these
sodium ions affects the action potential in muscle cells
(myocytes) too. There is no communication between
neurons, the message can't move down to the muscles,
there is no muscle activity. 1. Axon. 2. Neuromuscular
Junction. 3. Myocyte (muscle fiber). 4. Myofibril.
14. Explain how tetrodotoxin is involved in the
development of hypotension and hypoventilation.

Tetrodotoxin blocks diffusion of sodium through the

sodium channel, preventing depolarization and
propagation of action potentials in nerve cells. It is our nerve cells that cause the contraction of the
muscles (diaphragm and inspiratory intercostals) that cause inhalation. If the nerve doesn't signal the
muscles to contract, we don't breathe... thus, hypoventilation.

Hypotension involves blood pressure - there may not be enough pressure to fully circulate blood (ex:
against gravity up to the brain). Autonomic nerves innervate the heart, and although it is autogenic,
the nerves modify the rate and strength of contraction.

15. Briefly describe the role of the autonomic nervous system in human physiology. What are
the two divisions of this system?
Autonomic nervous system (ANS) - the branch of your peripheral nervous system that regulates the
functions of your internal organs (heart, stomach) and also controls your smooth, cardiac muscles and
your glands.

Effects on organs and muscles and glands are NOT consistent

ANS makes constant involuntary, fine-tuned adjustments to your body based on what signals your
central nervous system is picking up (ex: changing body temperature, sending extra blood to a
particular area, slowing your heart beat, etc).
*EFFECTS CHANGE DEPENDING ON THE SITUATION YOU’RE IN AND WHICH PART OF
YOUR AUTONOMIC SYSTEM IS IN CHARGE AT THAT MOMENT*

ANS = divided into:

- Sympathetic: dedicated to amping you up and preparing you for activity.
- Sounds internal alarm bell
- Sympathetic fibers = thoracolumbar
- Parasympathetic: talks you down, undoes what the sympathetic nervous system (its “foil”)
did.
- Maintaining body and conserving energy
- Parasympathetic fibers = craniosacral (above and below sympathetic fibers)

Nerves of these two originate at different parts of the body

16. Atropine was administered in the ED as part of Dr. Westwood’s care. What effect did it have
on his vitals after it was administered? Atropine acts as an antagonist within the central nervous
system, which means it acts as a blocker of specific cellular functions. What part of the
autonomic nervous system does atropine block to produce its effect on Dr. Westwood?

Brought up the beats per minute, increased heart rate, blocked ACh receptors in parasympathetic
nervous system.

In general, atropine counters the "rest and digest" activity of ​glands regulated by the
parasympathetic nervous system​. This occurs because atropine is a competitive,
reversible antagonist of the ​muscarinic acetylcholine receptors (​acetylcholine being the
main ​neurotransmitter​ used by the parasympathetic nervous system).

Atropine is a competitive antagonist of the ​muscarinic acetylcholine receptor types M1,

[24]​
M2, M3, M4 and M5.​ It is classified as an ​anticholinergic drug​ (​parasympatholytic​).

17. In your first experiment, you generated action potentials in axons of large neurons obtained
from squid in the presence of this new toxin. You found that after depolarizing, the membrane
potential remained positive for an extended length of time, and the repolarization was often
extremely delayed. Draw a graph (membrane potential in mV vs. time) to illustrate this effect.
18. As you continued to experiment with higher concentrations of the toxin, you found cases
when the cell could not repolarize at all, or if it began to repolarize, it would immediately
depolarize again. Using this description and the description in the previous question, describe
how this toxin acts on voltage-gated sodium ion channels.

Nervous System
● Hola esto

caso clinico 1
The patient was a 70-year-old man and his medical history included a surgical procedure for

esophageal cancer​ at 8 months before poisoning. On the day of poisoning, the patient caught two

puffer fish at a nearby beach in the morning and brought them to his home, where he thoroughly

kneaded the flesh and livers of the fish in water and then soaked them in water for 8 hours. After that,

he ate some flesh raw and the other after briefly boiling. In addition, he boiled the liver for 20 minutes

before eating it. Approximately 10 minutes after eating the fish, he began to experience tongue and

peri-oral ​paresthesia​. Because he then started to exhibit symptoms of inarticulation, he suspected

puffer fish poisoning by himself and visited the emergency room (ER) of our hospital approximately 1

hour after ingestion by his own car with his family.

On ER admission, paresthesia of extremities, weakness of both lower limbs, difficulty in respiration,

and ​dyspnea​ were revealed. He could not stand up or speak. The patient was also in a state of

agitation. His spontaneous respiration was 25 breaths/min, SpO2 was 96% (room air), chest

movement was poor, heart rate was 71 beats/min with normal sinus rhythm, blood pressure was

172/82 mmHg with no cold extremities, and Glasgow coma scale score was 12 (E4, V2, M6). ​Table 1

shows laboratory data on arrival. Blood gas analysis indicated respiratory alkalosis and biochemical

examinations indicated very slightly elevated lactic acid levels. After the patient was admitted to the

intensive care unit, he was intravenously administered buprenorphine (0.2 mg) and midazolam (5 mg)

and underwent intratracheal intubation. Volume controlled mechanical ventilation was started.

https://www.omicsonline.org/open-access/a-case-of-severe-puffer-fish-poisoning-serum-tetrodotoxin-
concentration-measurements-for-days-after-ingestion-2161-0495.1000-226.php?aid=39440
http://www.scielo.br/pdf/jvatitd/v22/1678-9199-jvatitd-s40409-016-0057-8.pdf