Report HYPP

7/29/2019 Report HYPP

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Balidiong, Pelmark GambalanBaluyot, Margarete Rose Encarnacion

Bantigue, Marissa Jean JaminalBarrientos, Jesse Cyrus Vamenta

Bautista, Biancca Camille Ong


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OVERVIEW


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Myofibrils are

surrounded by

calcium-

containingsarcoplasmic

reticulum.


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Overview of the process


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The muscle fiber is

stimulated.


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The muscle fiber is

stimulated.

Ca2+ ions are released.


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End-on view ofthick & thin

filaments, showingthe effect of calcium

ions after release

from the S.R.


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The muscle fiber is

stimulated.



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The muscle fiber is

stimulated.


Thin filaments move to

middle of sarcomere.


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Calcium attaches to troponin/

tropomyosin; they roll away,

exposing the active site on

actin.


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Myosin

cross-bridges

attach to active

site on actin.

After attachment, the

cross-bridges pivot,

pulling the thin

filaments.


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A fresh ATP replaces

the ADP + Pi, allowing

myosin and actin to

detach.

Energy from the

splitting of the

fresh ATP allowsrepositioning of

the myosin head.


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This leads back to Step

1, which continues the

cycle as long as calcium

ions are attached to

troponin/tropomyosin.


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The muscle fiber is

stimulated.





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The muscle fiber is

stimulated.




Muscle fiber contracts.


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The muscle fiber is

stimulated.




Muscle fiber contracts.

Muscle tension increases.


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What is PRIMARY HYPERKALEMIC PERIODIC PARALYSIS

Hyperkalemic periodic paralysis is a condition

that causes episodes of extreme muscle weakness,usually beginning in infancy or early childhood. Most

often, these episodes involve a temporary inability to

move muscles in the arms and legs. Episodes tend to

increase in frequency until about age 25, after which

they may occur less frequently.

How common is hyperkalemic periodic paralysis?

Hyperkalemic periodic paralysis affects an

estimated 1 in 200,000 people


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What GENES are related tohyperkalemic periodic paralysis?


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SCN4A gene

sodium channel, voltage-

gated, type IV, alpha subunit


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gene belongs to a family of genes that

provide instructions for making sodiumchannels

These channels, which transportpositively charged sodium atoms

(sodium ions) into cells, play a key role

in a cell's ability to generate andtransmit electrical signals


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Molecular Location on chromosome 17


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How do people inherit

hyperkalemic periodic paralysis?


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It is an autosomal dominat penetrance and aregenetically heterogeneous

Most cases of HyperPP, as well as the allelicdisorders paramyotonia congenita and K-

aggravated myotonia, are caused by mutations

in SCN4A

The most common are the missense mutationsT704M and M1592V accounting for 75% of

affected individuals while other point mutationsaccount for the remainder of affected individuals


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most abundant intracellular cation

Important in:maintenance of cellular membrane potential,

homeostasis of cell volume, and transmission of

action potentials in nerve cells


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Hyperkalemia

refers to the condition in which

the concentration of the

electrolyte potassium (K

+

) in theblood is elevated

Normal serum potassium levelsare between 3.5 and 5.0 mEq/l


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Paralysis

The loss of the ability to move (and

sometimes to feel anything) in part or

most of the body, typically as a result ofillness, poison, or injury


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Contractures

The abnormal shortening of

muscle tissue, rendering the muscle

highly resistant to passivestretching.


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NORMAL sodium ion channel is a large molecule in the cellmembrane of muscle fiber. It consists of foursubunits arranged in pairs around a

central opening.When muscle receptors bind neurotransmitter

released from a nerve, normally the sodiumchannel opens to allow sodium to pass through

the muscle cell. This initiates a chain of reactionscausing the muscle to contract. In the recoveryphase that follows muscle contractions thesodium channel closes.

Muscle paralysis


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In HYPP

the sodium channel closes too slowly and thussodium ions continue to flow into the muscle.

This leads to oversensitivity and stiffness in themuscle (myotonia).

If the sodium channel remains open, the musclewill become desensitized and finally paralysed.

At the same time, potassium ions are releasedfrom the muscle and the concentration of

potassium in the blood rises.


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Mechanisms of Episodic Weakness

Extracellular K+ increase: 2 to K+ intake, or Rest after exercise

Membrane depolarization: Mild

Na+ channels open: Abnormal Na+ channels to non-inactivating mode

Persistent inward Na+ current

Extracellular K+ increaseSustained depolarization of muscle membrane

K+ efflux

Inactivation of normal Na+ channels

Loss of electrical excitability of muscle membrane

Weakness


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CASE PRESENTATION

PRIMARY HYPERKALEMICPERIODIC PARALYSIS


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PRIMARY HYPERKALEMIC

PERIODIC PARALYSIS

A 9 yr old boy had attacks of muscle paralysis,

characterized with contractures of the

affected muscle. Later in the attack, themuscles become paralyzed. Serum K+ during

the attack was elevated. However, biopsy

showed diminished level of intracellular K+compared with control muscle. Basal tissue

activity of Na+, K+-ATPase is normal.


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PERIODIC PARALYSIS

Electrophysiologic studies showed

that during the attack, the excitability,

conduction time of motor neurons andfunction of neuromuscular junction are

normal. However, the magnitude of the

resting membrane potential of skeletal

muscle is decreased compared with

control muscle fibers.



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PERIODIC PARALYSIS

Electromyography shows that early in

the attack, the muscle contractures are

associated with spontaneous actionpotentials in the affected muscle fibers.

During the paralytic phase of an attack,

the muscle cells become excitable. The

paralytic attack was relieved by insulin

injection.


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Symptoms

CASE

Attacks of muscleweakness characterizedby pain with

contractures of theaffected muscle.

Later in the attack, themuscle becomeparalyzed.

HPP

Come and go

Common shoulders and hips, mayinvolve arms and legs

1 2 hrs to a day

Occurs resting p activity,awakening

Trigger: High K+ food, exercise,exposure to cold

Normal muscle strength betweenattacks.

Associated myotonia


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Signs and Tests

CASE

K+ during the attackwas elevated.

Biopsy of muscle:

diminished level ofintracellular K+compared withcontrol muscle.

Basal tissue activity ofNa+, K+ -ATPasenormal

HPP

Blood tests: a wk period

Family history: mutationlinkage of SodiumChannel

During attack: decreaseor absent muscle reflex

ECG: Inactivation ofsodium channels- sluggish

conduction of electricalwave

EMG:myotonia

Muscle biopsy


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Explain the following mechanism

Increased serum K+

Decreased muscle cell K+


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Increased Serum K+

Excessive production:

oral intake and tissue breakdown

Mutation on linkage to the Na+

channel expressed in muscle. Sodiumchannels fail to activate properly.


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Decreased K+ in muscle cell

In Primary Hyperkalemic Periodic Paralysis

the sodium channel closes too slowly andthus sodium ions continue to flow intothe muscle. At the same time, potassium

ions are released from the muscle and

the concentration of potassium in theblood rises.

E l i h M h i


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Explain the MechanismDecreased magnitude of resting membrane potential of skeletal muscle during

attack

Elevating extracellular K+

and decreasing theintracellular level of K+

The decreased magnitude of the RMP initially

brings the muscle cells closer to threshold for firing an

action potential.

Small fluctuations in the resting membrane

potential may reach threshold.

Spontaneous action potentials and contractions ofskeletal muscle cells

Leads to the contractures experienced by the

patient in an attack.

Si ifi f d i b


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Significance of decrease resting membrane

potential of skeletal muscle

Prolonged depolarization of the muscle cellplasma membrane will lead to voltage

inactivation of Na+channels in the membrane, which

will result in the muscle cell's being unable to fire anaction potential.

This is believed to be the cause of the paralyticphase of an attack and is supported by the

observation that during the paralytic phase, the

patient's skeletal muscle cells may be electrically

inexcitable.


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What is the significance of the following:

Normal excitability and conduction timesof motor neurons

Normal function of neuromuscular junction

Biancas part


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How insulin injection can terminate the

paralytic attack in this case?

Biancas Part


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PROGNOSIS

Sometimes attacks disappear later in life on

their own. However, repeated attacks may lead

to permanent muscle weakness.

Hyperkalemic periodic paralysis responds

well to treatment. Treatment may prevent, and

may even reverse, progressive muscle

weakness.


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Possible Complications Kidney stones (a side effect of medicine used to treat the

condition)

Irregular heart beat

Difficulty breathing, speaking, or swallowing during attacks

(rare)

Muscle weakness that slowly continues to get worse


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Treatments, Interventions and Prevention

Be in contact with a pediatric neurologist, a dietician and a specialistpediatrician.

Medications that reduce potassium levels in the blood.

Examples of substances prescribed include:

thiazide diuretics, acetazolamide and dichlorphenamide.

Hydrochlorothiazide is also effective and has fewer side effects than

acetazolamide.

salbutamol

mexiletine

A low potassium, high carbohydrate diet may also help prevent

attacks, as may avoiding fasting, strenuous activity, or cold

temperatures.


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Information sites:

Biancas part


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Documents

Report HYPP