Clinical Features of Narcolepsy

Hello friends!!

This is the second one in the four-post series on Narcolepsy. So let's begin.

Narcolepsy is not just a disorder in which the patient sleeps a lot, believe it or not the number of hours in a day spent in sleep by the narcoleptic is no greater than that of a normal individual!!

Narcolepsy is characterized by the classic tetrad of excessive daytime sleepiness, cataplexy, hypnagogic hallucinations and sleep paralysis. There is also a disorder of REM sleep. So let us try to understand these major clinical features.

The essential disorder is one of frequent attacks of irresistible sleepiness several times a day, usually after meals or while sitting in class or in other boring and sedentary situations. Now let us try to picturize the patient.

The eyes close, the muscles relax, breathing deepens slightly and it seems that the individual is dozing. A noise, a touch or even the cessation of lecturer’s voice is enough to awaken the patient. So the periods of sleep rarely last longer than 15min unless the patient is reclining, or if he is in an appropriately comfortable situation to sleep. At the conclusion of the nap, the patient feels somewhat refreshed.

Cataplexy refers to a sudden loss of muscle tone brought on by strong emotion- that is, circumstances in which hearty laughter or, more rarely, excitement, surprise, anger, intense athletic activity. So you can basically “tickle” a Narcoleptic into a Cataplectic state. 

The patient’s head will fall forward, jaw will drop, knees will buckle with sinking to the ground – all with perfect preservation of consciousness (scary, right?). Most attacks of cataplexy are partial, eg., only dropping of the jaw or weakening of the knees.

In about half the patients, there is hypnagogic hallucination and sleep paralysis. Please do not confuse sleep paralysis with cataplexy; sleep paralysis is brief loss of control(not tone) of voluntary muscles that occurs during the period of falling asleep or less often when awakening.

There are two terms which we should know, hypnagogic and hypnopompic. Hypnagogic or predormital refers to the period of falling asleep while hypnopompic or postdormital refers to the period of awakening. Sometimes there may be vivid and terrifying hallucinations with or before the onset of sleep paralysis, which may be visual, auditory, vestibular or somatic, called hypnagogic hallucinations.

That's all. Do go through the other posts in this series.

Role of Orexins in Narcolepsy
Diagnosis of Narcolepsy
Treatment of Narcolepsy

-VM 

Role of Hypocretins/Orexins in Narcolepsy

Hello friends!!

This is the first of the four-post series on Narcolepsy.

So let's start. The hypocretins were thought in the past to regulate feeding behaviour and energy metabolism, the word “orexin” is derived from the Greek word for appetite. But later through animal experimentation it was found that in mice, inactivation of two hypocretin receptors reproduces Narcolepsy.

First of all, let us learn that monoaminergic neuronal projections from Tuberomammilary nucleus(histaminergic), Locus Ceruleus(noradrenergic) and the Raphe nucleus(serotonergic) inhibit the Ventrolateral Preoptic Nucleus(VLPO) of hypothalamus.

To put it simply, the transition between sleep and waking is determined by the state of activity of the VLPO. Now imagine a see-saw, on one side we have all these nuclei wanting the person to wake up and on the other side we have VLPO forcing the person to sleep. Whoever gets heavier, metaphorically speaking, chooses the person’s state. 

So what’s the role of orexin/hypocretin ? We can say that it enables a smooth transition between wakefulness to sleep by reinforcing the monoaminergic firing from those three nuclei; hence it indirectly inhibits the VLPO. Hence if we remove orexin from the picture, the person will fall asleep immediately without being able to control; and roughly this is what occurs in Narcolepsy. 

That's all. Do go through the subsequent posts in this series.

Clinical features of Narcolepsy
Diagnosis of Narcolepsy
Treatment of Narcolepsy

-VM

Basics of Immunoglobulin G

Hey  readers!! ,So I have started with immunoglobulin section where I will be putting facts about a single immunoglobulin ,so today it is IgG!.

Immunoglobulin G or IgG occupies about 80% of serum antibodies.! .It's normal concentration is about 8-16mg/ml.They are created and release by plasma B cells .
There are two unique facts about IgG
1)It's catabolism.
2)Suppression of homologus antibody synthesis by a feedback process.

What's unique in catabolism?.
Well we can say body has complete control over the catabolism and to make it simpler let's say body and IgG both acts opposite to each other !.(Just a saying :p,Infact we know IgG works for body).For example In some diseases like chronic malaria ,kala azar or myeloma IgG level rises and as we know body has complete control and it acts against it So, IgG synthesis its gonna catabolised it rapidly !
Conversely,In hypogammaglobulinemia IgG given for treatment is metabolised slowly.

Suppression of homologus antibody synthesis
IgG has another unique property of suppressing the antibody synthesis which looks like it or performs similar kind of functions or simply homologus antibody.
Now let's say IgG is quite insecure about its true but dominating love -"Body". It doesn't want any competition so it kicks away all the antibodies which looks like it or perform similar function like him
(Such a insecure antibody it is  !)and this unique property is utilised in the Iso-immunisation of a women by administration of anti-Rh(D) IgG during delivery.

Well some more characteristics of our hero IgG is
It's the only maternal immunoglobulin that is transported across placenta and provides "Natural passive immunity"in new born (Not present in infants )

It has 4 subclasses due to presence of gamma 1,gamma 2 , gamma 3 and gamma 4 chains .

IgG1=65%
IgG2=23% (By the way 23 is also half life of IgG)
IgG3=8%
IgG4=4%

Here are functions of IgG molecule

Immunohemolytic anemias part-2

Hello readers, here is the continuation of the previous topic, Immunohemolytic anemias. Today we will discuss the next two types, its more like winter special.

B) Cold agglutinin type-  Cold agglutinin derives their name from the fact that they show maximal activity at temperature lower than normal body temperature.
It is present in low titres in healthy individuals.
Physiological cold agglutinin develops naturally after birth as a result of change in expression of Red cell antigens and reacts maximally at 4°C.
While pathological cold agglutinin maximally reacts at around 28-31° C and tend to occur at very low titres.

Mnemonic is "Cold MILL"
C     -  Complement mediated hemolysis. 
         
M    -  IgM is the causative antibodies

  I     -  Cold agglutinin antibodies appear  
           transiently following Infections 
            [Mycoplasma pneumoniae, EBV,
            HIV, influenza virus, CMV]
          - I antigen is the most common
              target
           
L     - Chronic cold agglutinin AIHA is
          associated with Lymphoid 
           neoplasm
          (esp B cell neoplasm), leukemias     
           like CLL

Mechanism- IgM binds to red cell where the temperature may fall below 30°C. It agglutinates red cells, and fixes complement rapidly. As blood recirculates and warms, IgM is released,but sufficient deposition of complements leads to phagocytosis of affected red cells in spleen, liver, bone marrow.

Clinical presentation- Exerts their pathological effects either via hemolysis and red cell destruction in RE system predominantly liver or by vaso occlusion due to agglutination.
-Mild anemia, purplish discoloration of fingers, toes, earlobes [ Acrocyanosis],  mild hepatospleenomegaly,
Raynaud phenomenon in peripheral cold exposed parts.

C) Cold hemolysin type -
Also known as paroxysmal cold hemoglobinuria.
It's a rare fatal disorder causing intravascular hemolysis and hemoglobinuria when auto antibodies binds to P blood group antigens in cool, peripheral regions of body.

Paroxysmal Cold HemoGlobinuria:
P- P blood group antigens
C- Complement mediated lysis occurs.

    IgGs auto antibodies binds to red cell in  
    cool peripheral regions, Complement
    mediated lysis occurs when affected
    red cell recirculates to warm regions,
    because complement cascade 
    functions
    more efficiently at 37°C

H- Hemoglobinuria
G - Auto antibodies belong to class IgG

Symptoms of the patients aggravates on exposure to cold.

Winter is coming, we know what's coming with it.
Stay warm :)

Immunohemolytic anemias part-1

Hello awesomites!
This is my very first post, so am starting with my favorite subject Hematology.
Today's post is about Immunohemolytic anemias, commonly ignored type of anemia

Also referred as Autoimmune hemolytic anemias(AIHA)
Where antibodies are responsible for premature destruction of red blood cell.
Types- warm antibody type
            - cold agglutinin type
            - cold hemolysin type

Warm antibody type  -  It is the most common type of AIHA.
you can remember it by mnemonic
" WARM GRILLED "
W - Warm because, antibodies are active  
       at 37°C
A -  Associated with other Autoimmune        
       disorders ( secondary causes like 
       SLE)
R - Red cell hemolysis is mainly
      extravascular
M- Moderate spleenomegaly due to
       hyperplasia of splenic phagocytes      

G- Ig G class - most common causative
      antibodies ( IgA sometimes too)

R- Rh blood group antigens are the main
      target 
I- 50% primary cases are  Idiopathic
       Secondary causes can be

L- Lymphoid neoplasm

ED-  Exposure to Drugs.
Examples - penicillin, cephalosporins, quinidine, methyl dopa etc

Mechanism - A) Antigenic drugs-
Drugs such as penicillin binds to red cell membrane and they are recognized by the antidrug antibody. The antibody either recognizes the drug and bind to it or both drug and membrane protein,ultimately results in hemolysis.

B) Tolerance breaking drugs- In drugs such as methyl dopa, antibodies are formed against red cell antigens particularly Rh antigens.

Stay awesome✌️

Nasal spray that prevents suicide.

0Hello readers! Being in medical field we are quite acquainted with the word "Stress out" .Todays article is just about a simple nasal spray that can prove to be a boon to entire human kind.(I think specially our field ! :p)

Everything in a brain is carried out by special substances called as "Hormones" .Even the simplest change in mood is concerned with hormonal changes.For example in first trimester of pregnency a rapid rise in estrogen and progesterone can cause mood swings in woman.Similary when there is depletion of hormones or its metabolites or less production of hormone this can leads to depression ,low -emotional state ,anxiety etc.Suicide can be triggered by serious illness ,can also be triggered by low self-esteem or emotional pain .
Scientists are developing a nasal spray that can prevent suicides! .This nasal spray consists of Thyrotropin releasing hormone(TRH) also known as thyroliberin . Thyrotropin is actually hormone released by hypothalamus ,it actually stimulate release of thyrotropin and prolactin from anterior pituitary.Recent findings have found out that TRH  also shows  anti-depressant and anti-suicidal effects.Thus preventing suicidal behaviour and depression.Researchers want to figure out ,a way to deliver it to a brain when it is given through nose  .Brain is protected by Blood brain barrier (BBB),which is acting has a hinderence to pass TSH to brain.
Clinically it is related  in spinocerebellar degeneration and disturbance of  consciousness in humans.Pharmacological form is known as protirelin.

I hope scientists find it soon how to cross  BBB  :p
Exams are near and I am already freaking out :p
Keep smiling :)
Have a day with high level of TSH in brain :)

~Ojas

Can virus kill cancer cells ?

Hello awesomites !Today's topic is short ,simple and easy to understand.

Cancer is basically a disease where there is abnormal growth of cells in body and sometimes it is also malignant that is ,it can spread from one organ/site to another.These newly formed cells can disturb normal cycle of other cells .When a  cell suffers DNA damage from cancer,a virus or radiation a group of protein complex MRN is sent to repair DNA.MRN is protein complex ,it consists of Mre11,
Rad50 and Nbs1 .In eukaryotes initial processing of double strand DNA breaks prior to repair by homologus recombination or by non-homologus joining.
When a DNA virus is present in the cell,MRN instead focuses on removing it.
If both DNA damage & a DNA virus are present in a single cell .The MRN complex is unable to manage both threats at once and ends up ignoring the virus .
These new findings imply that scientist might be able to form a virus that targets and  kills only cancer cells.

Keep smiling:)
Good day:)

Artificial skin

Hello awesomites !!! Today's topic is something that really has created revolution in the entire human race - "Artificial skin"

Skin is the largest organ of our body. It consists of three parts Epidermis, dermis and fatty layer. Epidermis serves as the protective layer of the skin, it prevents the entry of the pathogen into body with the help of sebaceous and sweat glands along with long chain fatty acids, and dermis consists of all the nerves, artery and veins that supply skin. Fatty layer maintain the body temperature.
A damage to the skin through burns causes loss of large number of plasma and it provides free entry to pathogens into body. Artificial skin was discovered by Loannis yannas & his colleague surgeon Dr John burke.

Artificial skin was discovered to replace bandages, which cannot seal large damage areas. Patients with extensive burns often die as bandages cannot heal their wounds completely. Even if patient survives some scars are left behind on skin. Artificial skin consists of collagen polymers. Collagen is protein found in skin. Artificial skin helps patient to grow skin without forming any scars. It has been commercially prepared under name as IntegraTM.

It is also used in plastic surgery and also in chronic skin wounds.
 
Ahh!    That's it :)
            Keep smiling :)
            Have a nice day!
      
~Ojas

Replacement to open heart surgery

Hello awesomites today I am gonna tell you something that is really -really interesting and fascinating !.
We all know how crucial is open heart surgery in some conditions, here is one of the alternative methods of open heart surgery.(For some conditions)

Alternative method :-

For the 1st time a new catheter technology was used in place of open heart surgery.
Cardioband is a low impact method to fix leaky mitral or tricuspid valve in heart. The catheter technology offers a minimal invasive alternative to heal a leaky valve. It enables the tightening of a leaky annulus in the heart. During this procedure, the band is placed around the open valves using catheter. It is served with anchors & tightened using a wire until the valve is fully closed. Until now , only treatment of leaky tricuspid was open heart surgery.

Now patient  previously thought to be inoperable will have chance to be treated.
University Zurich hospital successfully performed first tricuspid surgery using cardioband .

Have a happy day
Keep smiling:)

~Ojas

Monteggia vs Galeazzi fracture mnemonic

Hey Awesomites

While studying the Monteggia and Galeazzi fracture and dislocation today, I googled and came up with a mnemonic. GRUesome MURder helps us remember which bone is fractured and which one is dislocated.

GRUesome-
G: Galeazzi
R: Radial fracture (lower- third)
U: Ulnar dislocation

MURder-
M: Monteggia
U: Ulnar fracture (upper- third)
R: Radial dislocation

Also in Monteggia fracture, bone of medial side is involved.


Thats all
- Jaskunwar Singh

Top 10 series: Empagliflozin

Here is the video!

Migraine- Research updates

Hey Awesomites

Now that we are clear on the basics, here's another post on recent updates and studies on the concepts of causation and treatment strategies of migraine.

The basics: Migraine

Hey Awesomites!

Lets understand the basics of migraine here-