I walk up to the middle-aged woman who is terribly worried

This is the third time her husband is in the ICU

Each time, worse than the previous

This time, he is in a coma, and the reasons for him going into recurrent altered behavior remain elusive

Only one clue - cirrhosis

Shankar, her husband has diagnosed with cirrhosis just a two months ago

At the time, he had swelling of both feet and an evaluation revealed low platelets and features of cirrhosis on imaging

Absolutely no complications of cirrhosis

Complications of cirrhosis come in stages

Stage 1 and 2 feature changes associated with cirrhosis and high liver pressure (called portal hypertension)

Stage 3 and 4 is when clinical events in form of various complications take place

These include ascites (fluid in abdomen), vomiting blood or passage of black stools

In stages beyond these, patients develop features of liver failure - such as jaundice (defined as bilirubin levels > 3mg/dL) 

and brain failure (called hepatic encephalopathy or HE)

In natural history of the cirrhosis, HE happens in advanced stages and predicts early death

In HE patients progress through various stages

From slight memory loss and difficulty in calculation to slurred speech, confusion and finally coma

30%-45% of cirrhosis patients experience HE (prevalence or commonness)

Diagnosing HE is pretty easy - rule out other causes...

of brain failure or neurological dysfunction

So essentially, HE is a diagnosis of EXCLUSION

Other causes such as stroke, brain infections, brain tumors, intoxication, trauma etc.. has to be ruled out 

Once HE is diagnosed, then the most important part is to look for the...

reason for precipitation of HE

In the ER, Shankar was being put on the ventilator because he is in a coma and chances of aspiration of saliva into his lungs was very high and lung failure was very high

They were small, loving, close knit family

Father, mother and daughter

Their daughter was 22 years old, engaged to a gentleman and wedding was planned in three months

After the engagement, her father was diagnosed with cirrhosis and within two months of his diagnosis, he was admitted thrice with HE

And now in a coma, she was worried...

that she would end up on wedding day, without her beloved Appa

My colleagues take a detailed history - Shankar was a teetotaler, a sweet man who followed doctors orders to the T and worked hard to make ends meet

He was overweight

No drug use apart from what was prescribed



The first time he got sick, it started off with him mistaking the living room for the bathroom and was readying himself to urinate on the living room floor 

Disoriented and confused, he was rushed to a nearby hospital where he was diagnosed with HE and treated accordingly

The second HE attack came after 3 weeks - this time, he was disoriented while riding his bike and crashed onto a pole very close to his home

No brain injuries, and again, treatment for HE improved his condition and he was taken home

The third time, he went into a coma...

in front of my eyes

Time was running out and we had to find what was causing his recurrent brain failure

To make things worse, his liver functions were perfect and his cirrhosis was in stage 2 - HE is not expected in this supposedly stable stage

What was causing it?

When a patient with stable cirrhosis, presents with recurrent brain failure in the absence of identifiable causes for precipitation of HE it is called "spontaneous HE"

As we wait for the blood reports, we also send Shankar for a CT scan of the abdomen

This would help us...

identify an important cause for his supposed recurrent spontaneous HE

This is called as portosystemic shunts

Portosystemic shunts are LARGE blood vessels that form inside the abdomen in cirrhosis, when the liver pressure increases as the liver shrinks

When liver shrinks...

the pressure inside the liver increases and blood flow into the liver gets difficult

But blood has to flow around

Akin to a block on the highway and how vehicles take the bypass and service roads, for the blood to flow, new large blood vessels form which bypass the liver

These are called portosystemic shunts or PSS 

- they ferry the blood away from the liver and go straight into the system, including the brain

Without going into the liver, the bypassed blood is rich in ammonia - an important waste toxin that causes brain failure

In Shankar's case, we did not find any shunts and hence, large PSS as a cause for brain failure was ruled out

Meanwhile, the blood reports come
And everything was normal

Except two small things

Potassium levels - this was very low in Shankar
Ammonia - was raised

Low potassium levels - called HYPOKALEMIA is an important risk factor that can precipitate HE

So we had it
We found the cause for his HE this admission

When potassium levels drop, capacity for urea synthesis reduce in the liver (urea generation occurs in liver, UREA CYCLE)

and this leads to increase in ammonia which then cause brain failure

But also, when potassium goes low, it triggers conversion of amino acid glutamine in kidneys to excess ammonia

Excess ammonia then enters circulation, reaches brain and causes HE

Treatment was simple...

Correct potassium levels and Shankar will be fine

So we start potassium correction for Shankar and tell his wife and daughter that, things are going to be well

But we did not yet, have the reason for Shankar's recurrent brain failure

So we ask the family about reasons...

doctors who treated Shankar for the first and second attacks of brain failure gave them

'High ammonia', says his wife
'But potassium was also low Amma', says his daughter

I sit up, listen & ask, ' Both times?'

& they nod

'Can I see the discharge summaries'? I ask them

And we see something intriguing.

Shankar, during all his three attacks of brain failure had low potassium levels

This meant that not only he had recurrent HE, but he also had recurrent hypokalemia every time that gave rise to HE

Why was his potassium going low repeatedly? 

And we know it was time..

Time we stopped being super-specialists and got back to the heart and soul of real medicine

Internal Medicine - back to the mothership

Causes of low potassium is a huge list

But we were interested in causes of recurrent low potassium

And to get to it, we needed the help of the best thing ever in clinical medicine practice

Algorithms

So we pull up an algorithm and try to figure out how Shankar was losing potassium

But first, we looked at his drugs list.
A host of drugs can cause low potassium...

and Shankar was not on any such.

So we move onto the algorithm to figure out why this was happening

Investigations require us to look at 2 things

If potassium was lost through kidneys or non-kidney causes &

potassium level in urine & % (fractional) excretion of potassium

Following this pattern, we find that in Shankar...

Urine potassium was was high and his blood was alkaline (called metabolic alkalosis)
 
His admission blood pressures were on the higher side and this was true for every prior admission

And major potassium handling hormone,

called aldosterone, secreted by adrenal glands was low

This was strange
Low potassium
High blood pressure
Alkaline blood

All were common at every admission

High aldosterone levels can cause these

But Shankar had low aldosterone levels

This was called..

Pseudo (false) hyperaldosteronism

- condition that mimics high aldosterone levels, when in fact, aldosterone levels were low or normal

This can happen in rare causes which include:

Endocrine diseases
Dietary factors
Genetic causes



Endocrine and genetic diseases such as
Liddles syndrome
Apparent mineralocorticoid excess &
Congenital adrenal hyperplasia

DID NOT fit with main clinical and investigational features noted in Shankar

So we were left with three other causes

that could cause

Pseudo hyperaldosteronism or clinical features that mimic high aldosterone levels when levels were in fact low or normal

Licorice consumption
A seldom used drug called carbenoxolone
Grape fruits

So we get back to the wife and daughter and ask them his dietary habits and they deny excessive use of 

Licorice
Any other steroidal drugs
Grapefruits

Now we were truly lost
Without finding the cause of hypokalemia, Shankar was still at risk for brain failure because he..

was a cirrhosis patient and the chances of him getting through to attend his daughters wedding seemed very bleak

This depressed us and we did not know how to get through it

One day, while I was in the OPD, the staff comes in and tells me that Shankar's wife wanted to see me

I allowed her the time because I knew that we did everything we could to get to the root cause.

Even though Shankar would improve and get discharged from this episode (he was getting better on the ventilator, showing signs of waking up), we were not sure about his future.

The wife walks in and looks at me and I compose myself to apologize to her, because we thought we could do it, but we failed her too.

She speaks. 'Doctor, I thought long about the diet queries you asked me. And even though he did not consume any of those fruits you...

mentioned, he was taking some laxative powder.'

I sit up and ask her the name of the powder

She says she did not know, because he kept it inside the bathroom shelf & she never looked at it.

Cirrhosis patients are usually prescribed lactulose - a safe laxative that helps..

pass soft stools and also reduces ammonia

Lactulose did not suit Shankar - because a common side effect is excessive bloating and hence he went for some other laxative option, the name only he knew

'Only he can tell us and for that he has to be weaned off the ventilator'..

I tell the wife.

Now every bit of energy and focus from the critical care team and Hepatology unit was to get Shankar off the ventilator, so that he can tell us his diagnosis.

We go all out treating his brain failure as per evidence and by the book

Even though it took us..

more than a week to get to our goal, we finally wean off Shankar from the ventilator

His voice is raspy and he is weak
His swallowing is affected and he is dazed

The critical care nursing team do an intense job on rehabilitating him from speech, swallow and nutritional..

point of view.

And after another week in the ICU, Shankar is finally shifted out to the room

His potassium levels are fine
His blood pressures are fine
His blood is no more alkaline

And that day finally came, when on rounds, I could ask him about the powder he was having.

Kayam Churnam is a traditional Ayurvedic medicine used to treat constipation.

It contains Senna leaves which are known herbal laxatives and more importantly, Yashtimadhu or Glycyrrhiza glabra - also called Licorice.

Licorice consumption has been very strongly associated..

with low potassium.

Excessive licorice intake is a well-known cause of hypertension 

The licorice component glycyrrhizin inhibits an enzyme in the  kidney

This leads to rise in the hormone cortisol level leading to loss of potassium and increase in blood pressure!

The problem with Kayam Churnam and products that contain Senna laxatives is that they reach a threshold and then they do not work, unless doses are increased

Across 2 months of daily use, Shankar had slowly & steadily increased Kayam use which led to severe potassium loss..

leading to hypokalemia which thereafter precipitated hepatic encephalopathy or brain failure.

Licorice herbal products MUST BE taken with caution especially in high risk patient groups such as cirrhosis

They may appear and are marketed as safe, but truth is not always sweet

After spending almost three weeks in the hospital, Shankar was finally discharged home

Back home, first thing he did was throw away Kayam Churnam out the window

Shankar teary eyed, watched his daughter dance with her husband on the day of her wedding

He sent me a message..

on that day.

It did not contain any words.

Only two emoticons

This one <3 and :-)

It has been two years

Shankar has never had a brain failure since the last time we fought for him and he fought on the ventilator.