Why do we feel sleepy when we are sick?

Hellooo Everybody,
Let's delve into some sleep physiology and learn about some sleep producing substances breifly!

The chemical agents which might be responsible​ for induction of sleep have been obtained from experiments on sleep-deprived animals.
The first experiments of this type were performed by Henri Pieron in 1913 on dogs. He demonstrated that dogs receiving CSF from sleep-deprived donor dogs slept for hours, while the recipients of CSF from normal donors remained awake. Recent work has confirmed these observations and identified several candidate sleep producing substances (SPS)

Sleep-deprivation presumably leads to a rise in the production of these substances in the brain tissue, cerebrospinal fluid,and even urine, through a negative feedback effect.

The best known SPS :
1) Muramyl dipeptide (MDP)
2) Delta sleep-inducing peptide (DSIP)
3) Arginine vasotocin (AVT)
4) Interleukin-1 (IL-1).

Besides these, there are about 20 more putative sleep-inducing factors.

Most of the known sleep producing substances induce Slow Wave Sleep.

After learning the physiology let's answer our question:
Muramyl dipeptide (MDP) is a component of bacterial cell( which acts via IL-1.) walls ,whereas IL-1 is released in infections.
IL-1 potentiates GABA-induced increase in permeability to chloride at synapses causing inhibitory effect on the Brain.

Nitric oxide may be part of a second messenger system which mediates the effect of IL-1 on sleep.

Lastly, IL-1 induces release of growth hormone releasing hormone (GHRH) which in turn releases growth hormone. Growth hormone itself enhances REM sleep and inhibits Slow wave sleep.

This explains why we feel sleepy when sick!

IL-1 also induces fever, and is therefore also called endogenous pyrogen.  Antipyretics, such as aspirin, suppress the fever induced by IL-1 but do not affect the sleep-inducing effect of IL-1.
Like fever, sleep is a smart response  which perhaps helps recovery by compelling the patient to take rest.

Isn't it truly remarkable, how our bodies work!

Let's Learn Together!
-Medha.

Vascular smooth muscle: Effect of sympathetic stimulation mnemonic

Pancreatic beta cell: Effect of sympathetic stimulation mnemonic

Calcium channel blockers and muscles they act on mnemonic

Testosterone and Dihydrotestosterone

Hello awesomites today I am going to share my notes on functions of Testosterone and Dihydrotestosterone .

Testosterone is regarded as the circulating prohormone.In most of the target cells , testosterone is reduced to Dihydrotestosterone (DHT) which is more potent than the testosterone.

Testosterone function:

Remember: LISE
-LH inhibition .
-Internal genitals development .
-Spermatogenesis
-Erythropoiesis.

Dihydrotestosterone function

Remember :"PG says hair growth,behaviour changes and development of external genitals is due to DHT "

(Half of the things you all  must have got through it!)
PG-Prostrate growth .
Behaviour changes ,Sexual growth .
Hair growth .
External genital development.

Function which is done by both hormones?

-Increase in muscle  mass and strength of bones

Stay cool and awesome:)
~Ojas

ARDS pathophysiology Q&A

In Acute Respiratory Distress Syndrome (ARDS), what happens to the following parameters? (Increase / decrease / normal) 

Compliance
Pulmonary artery pressure
Pulmonary capillary wedge pressure
A-a gradient (Alveolar-arterial gradient)
PaO2 / FiO2

Answers given below!

Pathophysiology of myopathy caused during hypothyroidism and hyperthyroidism

Hello awesomites! Today's topic of discussion is - Myopathy in thyroid disease.

Interestingly, it is caused by both, hypothyroidism as well as hyperthyroidism.

What is myopathy?

It is a disease of muscle tissue where, ultimately, muscles get weak and are unable to perform work due to deficiency of ATP.

Why is there myopathy in hyperthyroidism?

The thyroid hormone is a catabolic hormone. Hyperthyroidism increases energy expenditure, glucose turnover, lipolysis, and protein breakdown (proteolysis). But here is the catch - Hyperthyroidism increases whole-body protein turnover and breakdown before any measurable changes in energy expenditure or glucose and fat metabolism, suggesting that amino acid and protein metabolism is an early and primary target for thyroid hormone action in humans. It was therefore concluded that the thyroid-hormone concentration may be an important factor in regulating muscle proteolysis. The altered protein metabolism causes myopathy.

Then, one may ask, why myopathy in hypothyroidism? Less thyroid hormone should lead to less protein breakdown, shouldn't it?

Well, this is a good question! Slightly complex and tricky to answer though. 

In hypothyroidism, there is abnormal glycogenolysis, defective mitochondrial oxidative metabolism and triglyceride storage.

Abnormal glycogenolysis and triglyceride storage: Less glucose is released and utilised because of this. The body starts using more proteins usually derived from muscles leading to myopathy.

Mitochondrial oxidative metabolism defect: Thyroid hormone is responsible for activation of bc1 complex also known as complex 3 & succinate dehydrogenase. Less activation of bc1 leads to less formation of ATP from glucose.... So again, the body switches to proteins from muscles as a source of energy!

That's all!
Stay cool :)

~Ojas

Fact of the day: Paradoxical undressing in fatal hypothermia

Hypothermia causes paradoxical undressing.

This typically occurs during moderate to severe hypothermia, as the person becomes disoriented, confused, and combative. They may begin discarding their clothing, which, in turn, increases the rate of heat loss. It is estimated that twenty to fifty percent of hypothermia related deaths are due to paradoxical undressing.

Why does this happen?

Hyperthermia in Pontine Haemorrhage

Hey guys!

This post will be focused on the pathophysiology of Hyperthermia in Pontine Haemorrhage( which may manifest as the Locked-in Syndrome, remember that super-awesome House episode? <3 )

1. First try the easy simple reason. Hypothalamus has been basically cut off from the body below pons and there has been Haemorrhage. Therefore, there will be a Sympathetic outflow causing peripheral vasoconstriction. Meanwhile the internal visceral organs are still functioning and consequently producing heat. So without hypothalamus, the body's ability to produce heat has transcended it's ability to lose heat.

2. The next reason is a bit "cooler", literally. Our body hates Hypothermia more than Hyperthermia, thanks to evolution. (Ice Age!!!) Now there is no central thermoregulation but peripheral one is still intact. And the peripheral thermoreceptors are much more sensitive to lower temperatures or basically cold environment. Once again, without the Hypothalamus, the body is defending itself too vigorously against Hypothermia as to contribute ironically to Hyperthermia.

3. This reason is the only one which you should know since this will explain how Baclofen, a GABA-B Agonist works to treat this Hyperthermia. Remember the Medial Forebrain Bundle, it connects Hypothalamus to a lot of structures, one of them being Nucleus Raphe in the Pontine reticular formation. This is a very crucial portal in control of Sympathetic nervous system outflow by Hypothalamus. Simply speaking, if the body is hot, Hypothalamus will send inhibitory (GABAergic and Dopaminergic) signals to this nucleus and if the body is cold, it will send excitatory (Glutaminergic and Serotonergic) signals. And apparently this connection is lost in Pontine Haemorrhage, so we substitute it with a drug.

P.S. Now you can guess how Bromocriptine and Apomorphine cause Hypothermia. :)

-VM

Right IJV for assessment of right heart hemodynamics

Hello

Internal jugular vein of right side is preferred for right heart hemodynamics. This is because-

Long QT Syndrome

Hey guys this post will be on Long QT syndrome as evident from the title :P.

In a brief introduction, it can be said that LQTS is simply because of abnormal myocardial repolarization most often due to a mutation in ion channel-associated gene. It can lead to fatal ventricular arrhythmias such as torsades de pointes.
So there is increased risk of Sudden Cardiac Death.

It has 3 common variants:

1. LQT1: Loss of function mutation in KCNQ1 gene. And in ECG you see early-onset broad-based T wave.

2. LQT2: Mutation in KCNH2 gene. In ECG T waves are of low amplitude, broad based and maybe bifid.

3. LQT3: Mutation in SCN5A gene. In ECG, there is prolonged ST segment with late-appearing T wave.

We use the ECG to diagnose LQTS and we estimate the probability by using Schwartz score.
Some of the important criteria are :-

1. QTc more than 480msec
2. T wave alternans (Varying amplitudes)
3. Torsades de pointes
4. Notched T waves in atleast 3 leads
5. Syncopal attacks with and without stress
6. Congenital deafness
7. Significant family history

That's all!

- VM

Fact of the day: Factors that are lost in stored blood

Hello awesomites !

What happens to blood that is stored in blood bank ?

Fact of the day: Genesis of the U wave

Hey guys!!

As you know the U wave in the ecg is seldom seen especially in leads V2 and V3 physiologically especially during bradycardia.
And it is seen pathologically in Hypokalemia.

So how is it generated?
If you are thinking due to repolarization of papillary muscles, let me tell you that this hypothesis is now obsolete.

There are three trending theories at present trying to explain it:

1. Delayed repolarization of the subendocardial Purkinje fibres.

2. Prolonged repolarization of the midmyocardium ( M cells)

3. After-potentials resulting from mechanical forces in the ventricular wall.

That's it!

-VM

Cushing's Reflex in Meningitis : Mnemonic and Explanation

Hello everyone !
Another short post on a very important triad. Cushing's!

Cushing's reflex
It occurs in response to raised Intracranial Pressure (ICP/ICT)

Mnemonic : 

HIB

H - Hypertension
I   - Irregular Breathing
B - Bradycardia

Mechanism :
So just imagine :
Due to some reason you develop an increase in the ICT.
We know that blood flows from High Pressure to Low Pressure. Generally , the CSF pressure is lower than the BP.
However after a point , the ICT is bound to become equal to or even more than the systemic BP!
If that happens , the blood flow to the brain is decreased and the Brain can get ischemic (cause the Cranial pressure would be higher. So the body won't be able to pump the blood into it.)

Thus, in order to compensate for this , the sympathetic system is activated. The body's peripheral vessels undergo constriction to raise the BP. This would keep them at a higher pressure than the Cranium thus keeping the blood flow intact for a while at least. This causes the Systemic Hypertension.

In a way it's the last ditch effort to save the brain!
Due to sympathetic stimulation the respiratory centers get stimulated too and it's all weird so it causes Irregular Respiration.

Now you'd expect Tachycardia when there is so many Sympathetic juices flowing through your body.
But no. Things aren't as simple as that.

The aortic baroreceptors sense the increased BP and end up decreasing the Heart Rate. Resulting in Bradycardia. So in a way that's the 2nd phase of this Reflex!

The Reflex serves as a marker of raised ICT as that is the event that puts the whole cycle into place.
This generally occurs as the body's last resort to restore blood to the brain.
What a wonderful Homeostatic mechanism !!

Hope this helped !
Stay awesome !

Reynolds pentads

Hello readers ! Today's blog is sweet and simple.

Reynolds pentads are collection of signs and symptoms appearing when there is obstructive cholangitis -infection of bile duct usually caused by bacteria .Following are the diagnostic features of the reynolds pentads with simple  mnemonic.
   RJ -FHC.
R-Right upper quadrant pain .
J-Jaundice .
F-Fever .
H-Hypotension.
C-Confusion .

By the way the first three diagnostic features are also called as Charcot's triad so we can also say Reynolds traid is combination of charcot's triad with low blood pressure and mental confusion .

Stay awesome:)

~Ojas

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

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

The SAAG solution (Serum-Ascites Albumin Gradient simplified)

Yo people!

A good friend of mine asked me to review the concept of SAAG. So let's dive into a "Puddle" of ascitic fluid. :P

As you guys all know, SAAG stands for Serum-Ascites Albumin Gradient and it helps to differentiate the causes of ascites. What it means is pretty self explanatory, it is the difference (gradient) between the levels of albumin (a plasma protein) in two compartments i.e. Serum and Peritoneal fluid.

The basics :Parkinson's disease

Hey,Hello! awesomites ,this blog is just a small review of some old and new things I learned about Parkinson's disease.
The very first thing I learned is:- parkinson's disease and parkinsonism are two different terms !!!.
-Parkinsonism is a complex term it includes many symptoms while parkinson's disease is a progressive neurodegenerative disorder .
-Parkinosons disease is actually cause of parkinsonism .
       Let's start with Parkinson's disease
-Main cause is decrease dopamine secretion in body mainly due to injury to substantia nigra which sends dopamine secreting nerve fibers to caudate nucleus and putamen.
Signs and symptoms:
- Characteristics features is tremors .Tremors occurs during all walking hours and therefore it is a type of involuntary tremor in case of cerebellar disease there is an intension tremor because tremors are seen when patient perform any work.
-Also  festinant gait is found
-Akinesia is also seen
-Lead-pipe rigidity is seen earlier in hands and legs followed by neck and trunk.

Causes:
-Any  serious injury that affects dopamine secretion !
-Also some medication which decreases dopamine secretion or blocks dopamine receptors.
-Apart from that certain drugs also induces Parkinson's disease  like drugs used to treat schizophrenia and other neuroleptic drugs like
Clozapine.
Risperdal.
Quetiapine.
Apart  neuroleptic drugs,others drugs  like prochlorperazine,metoclopramide.
Also calcuim channel blockers causes Parkinson's

Drug induced Parkinson's remains same ,it doesn't progress

Categories of drugs used for treatment of parkinsonism:-
-Dopamine agonist.
-Anticholinergic.
-COMI inhibitors.

~Ojas