Study group discussion: Water intoxication syndrome

Water intoxication syndrome! I remember this from first year physiology!

How does water intoxication syndrome work? How much water does the person have to take?

The water that causes intoxication is mostly through intravenous fluids. I doubt a human being would have the capacity to drink enough water to cause an intoxication orally. I have heard of psychiatric disorders associated with a high water consumption though.

But if you're looking for a number - it's 16 ml/min

If you consume that much in any amount of time, you'll have exceeded intake more than the maximal urine flow.

Ummm, got it! it makes more sense than what I was thinking hahaha

Surely, drinking too much water would cause vomiting or something before the body would allow itself to become intoxicated?
Or massive impermeability of the kidney nephrons?

Does drinking too much water cause vomiting?   How permeable is the upper alimentary canal to water?  Could a large amount of water be absorbed before it reaches the stomach?

Too much water does cause vomiting! The most common symptoms suffered by this group were changes in mental status, emesis, nausea, and seizures. Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770067/

I think there have been documented cases of people drinking enough water to die.  I imagine it's very difficult, though, and therefore rare.

Mostly psychiatric patients.

Water intoxication also occurs in SIADH and surgical trauma.

Risk factors include low body mass (infants), endurance sports, competitive drinking or latrogenic.
Treatment normally follows strict fluid restriction. In more serious cases, diuretics or vasopressin receptor antagonists are given.

Similar to SIADH treatment!

You know the artist Andy Warhol? He died of water intoxication!

Oh.

Study group discussion: Drug therapy for asthma

Which is the physiological antagonist of histamine?

Acetylcholine?

No.

It's ephedrine or adrenaline.

Which are the classes of drugs used for acute control of asthma?

B 2 agonists.

Epinephrine.

Yes, epinephrine.. But that too comes under b2 agonist.

Steroids?

No, steroids is for long term control

Two more classes of drugs!

Methylxanthine? Theophylline!
Montelukast?
Ipratropium!

Yup. Second class is theophylline or aminophyline. The third class is anti-cholinergics.

But not montelukast..That's also for chronic use.

What is the function of montelukast?

Leukotriene receptor antagonist!

Leukotrienes when binding to their receptors it cause bronchoconstriction. Monteluekast used in maintenance therapy of asthma. But not useful in acute exacerbation.

Mast cell stabilizers, that is, ketotifen and sodium chromoglycate?

Mast cell stabilizers are also chronic for use.

And IgE antibody? Omalizumab?

That too for chronic use.

Even MgSO4 is used in acute management of asthma.

Yup.

Next one.

Why does use of aspirin cause asthma?

Arachidonic acid forms two type of substances via the cyclo-oxygenase and lipo-oxygenase pathways. Aspirin inhibits the cyclooxygenase pathway.
Hence, all of the arachidonic acid gets diverted to lipo-oxygenases.
And if you remember L4, B4 are the major mediators of acute attack of asthma.

Oh yeah.. That's why leukotriene antagonists are used, they inhibit LT C4 , D4

Exactly.

There are the major cause of bronchoconstriction!

As cyclo cycle is inhibited..arachidonic acid is used more in lipo cycle!

LT antagonists act on cysLT1!

Study group discussion: Low molecular weight heparin vs unfractionated heparin

Something regarding heparins! So which one is better to use? LMWH or UFH? Why?

LMWH (Low molecular weight heparin)

Why?

Less incidence of thrombocytopenia with LMWH!
Better bioavailability, t1/2 , APTT not affected.

Right. Why APTT not affected?

Because LMWH has more predictable pharmacokinetics and anticoagulant effect, LMWH is recommended over unfractionated heparin for patients with massive pulmonary embolism.

Because LMWH acts only on AT3... Does not have the scaffolding effect of UFH.

On which part it doesn't act?
LMWH doesn't affect on thrombin..

Yes! That's the answer!

LMWH acts on AT3 only and doesn't affect thrombin.

UFH acts by 2 mechanisms
1. On AT3
2. By providing a scaffolding on which AT3 can interact with Thrombin

In LMWH, the second effect is absent, hence less interference...

Yes!! Correct!!

Which situation you would prefer UFH?

For cardiac surgeries, UFH is preferred as it can be titrated dose - by - dose with protamine sulphate.

Cardiopulmonary bypass.

Why?

Cardiopulmonary bypass....Because it's effects can easily be reversed fully by protamine. And its more effective.

Exactly! Any conditions with high risk of bleeding we prefer UFH.

Yep. Cause we will be able to reverse if we give more heparin by giving protamine sulphahte same is not possible with LMWHs.

Why?

Because action of LMWH cannot be reversed completely..

Yes, correct. It's because of the molecular weight.

So which test would you like to do before deciding whether to give UFH or LMWHs?

Any other conditions?

Ok so in cases of advanced renal failure UFH are preferred over LMWHs

Now tell me why?

No idea.. Please explain!

So we would check creatinine before starting heparin

This was the test I was taking about! LMWHs are excreted renally.

Right...UFH is metabolised by liver

On the other hand UFHs are cleared by reticuloendothelial system.

Good work guys! Hope it helped!

Yes, thanks a lot!

What about pregnancy?

Are UFH still preferred or do you give LMWH?

The major limiting factor is the cost or HIT. Heparin is still ruling the world and saving millions of lives.

Also i heard..senior doctors still prefer UFH, inspite of LMW

Ummm!! I would say LMWHs are much better!! Many trials have proved that! It's only in certain scenarios that UFHs are preffered. Nobody wants to keep monitoring APTT so just making the life easy LMWHs are good!!

Yeah. But they are more experienced in using UFH.
This was told by our residents. If a senior external asks you whether UFH or LMWH is better.. Be diplomatic in your answer.

Ohh! Yeah that can be the thing!

Updated later:
And also an addition to a previous discussion on oral anti-coagulants. Why heparin is given for the initial 5 to 7 days, when warfarin has already been started?
One reason is the preformed coagulant factors need to get depleted before warfarin starts taking effect. The other reason is that in the initial days warfarin acts as a prothombotic. Cause it depletes protein c and protein s!

Study group discussion: Fixed specific gravity

What is fixed specific gravity? Like what is the cause?

Because of renal failure, the remaining functional nephrons undergo compensatory structural and hypertrophic changes,these compensatory changes result in urine that is almost isotonic with plasma.  Therefore, a patient experiencing renal failure will present with specimens measuring the same, or fixed, specific gravity regardless of water intake

Thanks! Is there any value associated with it? Numerals?

Low specific gravity in renal failure, which results in a fixed specific gravity is between 1.007 and 1.010.

Study group discussion: Fluoroquinolones

Fluoroquinolones with
maximum phototoxicity -  sparfloxacin
100% bioavailibity - pefloxacin
Highest efficacy against tuberculosis - moxifloxacin

I don't know what is the meaning of 100 % bioavailability.

100% bioavailability means no first pass metabolism. Usually achieved on IV administering.

Study group discussion: Beta blockers

Give me two reasons why..you don't give beta blockers to diabetics.

They mask the hypoglycemic symptoms

First reason correct.

Hint - It is something to do with the liver and beta 2 receptors.

Glycogenolysis decrease.

Yup..The beta 2 receptors stimulate the glycogen breakdown and glycogenolysis.

So if you give a nonselective beta blocker.. Not only will the patient not feel the coming signs of hypoglycemia but also the liver will fail to release glucose in the blood.

Side effects of beta blockers?

Bradycardia
Breathlessness is due to bronchoconstriction
Rise in lipid level

Why won't you prescribe a beta blocker to a young man?

Sexual distress? Not sure!

Sexual dysfunction..Correct!

Vivid dreams and insomnia, and sexual dysfunction is due to beta blockers central action on the brain. They cross the blood brain barrier.

In which type of arrhythmias are beta blockers especially indicated?
The ones atrial in origin.

In which type of arrhythmia beta blockers are contraindicated?

Heart blocks.

Why so?

Cause they reduce the heart rate further.. A side effect of beta blockers is to decrease AV nodal conduction and precipitate asystole. In other words, they increase the refractory period of AV nodal cells.

Study group discussion: Locked in syndrome and total locked in syndrome

What's locked in syndrome and total locked in syndrome?

The patient is conscious, well oriented to time, place and person but is unable to carry out any voluntary movement along with loss of reflexes. Everyone else thinks the patient to be in a comatose / coma state.

Some retained cranial nerve reflexes with eye movements to communicate with no limb movement.

Yes! But in total locked in syndrome, there's no eye movement.

In locked in syndrome, I think patient communicates through blinking of eyes.

Yes. But in total locked in syndrome, they cannot.

Study group discussion: Cool fact about GLP 1 agonists

Antidiabetic derived from lizard?

It's exenatide! GLP-1 agonist.

From the gila monster, is it?

Exactly!

Is it not given orally?

I hope not

No.. Parenteral.. Subcutaneous!

Also there are extended release of exenatide available. Taken as weekly injections.

Bydureon! Weird but true! Thank you!

Study group discussion: Side effects of thiazides

What are the side effects of thiazide diuretics?

Study group discussion: Drug causing hypertrophic pyloric stenosis

Exposure to which drug leads to infantile hypertrophic pyloric stenosis?
Hint: One of the macrolides.

Erythromycin?

Yeah, they have found the  association in the research that was conducted!

http://www.ncbi.nlm.nih.gov/m/pubmed/12090829/

If administered in the infant, can cause hypertrophic pyloric stenosis. Within 15 days of life, that is.

Interesting.

Study group discussion: Non contraceptive uses of condom

Non contraceptive uses of condom? I was asked this question in today's viva!

To prevent STIs.

Reduces incidence of HPV infection. 

Reduces chances of cervical cancer.

Condom pack to stop bleeding.

Condom to stop PPH.

Condoms can also be used as gloves for per vaginal examination where there is unavailability of gloves mostly in rural
areas. Strange but interesting fact!

Condoms are also used to cover the USG probe in transvaginal scan.

And there exists a thing called condom catheter.. Used for weaning people off from a regular foleys! Due to prolong use of foleys patient loses urge to micturate. Sometimes.. So we use condom catheter. Which is basically a condom plus a urinary catheter attatched to it.

For vaginoplasty used to make moulds.

In treatment of infertility, used for 2-3 months.

Study group discussion: Hyperuricemia

Why does pyrazinamide cause hyperuricemia?

I guess it competes with uric acid for excretion because it is a weak acid.

Ohh.. Didn't know this.

There's an interesting concept I heard learnt while studying the uric acid thingy - Why does alcohol ingestion have attacks of gout? Anyone wants to guess?

Consumption of alcohol produces gout because when alcohol is coverted to acetaldehyde, NAD is converted to NADH. More NADH causes conversion of pyruvic acid to lactic acid. Lactate is not metabolised and excreted to kidney... Increased lactic acid excreation causes decreased uric acid excretion and hence gout occurs.

Alcohol produces lactic acid which competes with uric acid.
Loop and thiazide diuretics also cause hyperuricemia through this mechanism.

Correct! We have a brilliant mind in the group! B)

A random review question from top of my head since its the topic of uric acid: Which ARB drug is a uricosuric?

Angiotensin receptor blocker, right?

Losartan.

Yup.

Low dose aspirin also competes with uric acid. High dose aspirin uricosuric by inhibiting absorption.

Wow..nice info!

Any condition causing inorganic phosphate depletion also causes hyperuricemia.

Why does phosphate depletion cause hyperuricemia though?

Hypophosphatemia leads to accumulation of AMP which is then converted into uric acid. Galactosemia fructose intolerance cause hyperurecemia through this mechanism.

Amazing concept!

I feel so jealous if you.. Biochemistry is like my biggest threat!

Updated later:
Recently, we had a discussion on hyperuricemia caused by diuretics. It was mentioned it is due to the resultant acidosis that causes hyperuricemia. I read something on those lines. Diuretics do cause acidosis cause of slight CA ase inhibitory action on the PT. Thus acidosis even caused is not very marked. They cause hyperuricemia primarily by competiting with uric acid to get secreted via the organic anion transporter in the PT. Plus as the E.C.F volume is depleted due to diuretics, there is also increased absorption of the secreted uric acid. That's what I read.

Study group discussion: 45 centimetres in length and tubes

What are structures in our body about 45 cms in length?

That's an odd question. As in why do we need to know / significance?

Just to remember! Examiner here asked us in viva.

The spinal cord, Umbilical cord, Femur, Thoracic duct.

I know the esophagus is 25 cm in length. And the length from the incisor is longer. Were you given a nasogastric tube in your viva?

No.

Nasogastric tube 104 cm I guess..?

Varies 105 cms or 75 cms Ryle's.

This is gonna sound really basic but umm.. Can anyone explain the difference between an infant feeding tube, nasogastric tube and a Ryles tube?

Ryles tube is nothing but nasogastric tube.. Used for both diagnostic and therapeutic purposes.

Ohh.. I thought nasogastric and Ryle's are different.

In infant feeding tube there are no lead shots like in Ryle's tube.. And it's 52 cm in length.

Infant tube is narrow.

Infant feeding tube is used in: Tracheoesophageal fistula
Choanal atresia
Imperforate anus
Poisoning
Upper GI bleed

Thanks!