Teaching file No 1 .A case of jaundice

Six year old girl brought with yellowish discoloration of eyes and urine for the last  one and a half months.

There was no fever any time in during the illness. No abdominal pain or discomfort.
Overall course was gradual onset and slow progress.
No significant bleeding manifestations, through bowel urine oral mucosa or skin.
She was not constipated and stool was normally colored.
No skin rashes or nodules.
No joint pain or swelling.
No alteration of sensorium or behavioral problems.Sleep was normal.
No recent weight loss.

 

 

Born out of non consanguineous marriage to 32 year old father and 25 year old mother,elder girl child is healthy. No family history of jaundice, blood transfusion,abdominal surgery.
No significant neurological / psychological  problems   in blood relatives.

She was born at term after normal pregnancy. Birth weight was normal, neonatal period uneventful . There was no significant jaundice at that time. All her developmental milestones were normal and now she is studying in first standard.
No significant illness in the past requiring hospitalization.
No drug intake from modern medicine or other systems of medicine.

No travel outside.

She is immunized update 

No similar illness in the neighborhood.

before discussion just go through the basics

discussion at the level of history

Any patient coming with history of yellowish discoloration of eyes or urine first point is to make sure that it is jaundice.ie staining with bilirubin,with elevation of blood level of bilirubin.Answer to this question is mainly by clinical examination of both eyes and by macroscopic examination of eyes and the dress or towels stained yellow.(of course this point can be confirmed by simple lab tests later)

Entities confuse us when a patient comes with discoloration of eyes 

1.First step One eye only yellow.This may occur because bleeding in and around eye may lead to local bilirubin production by macrophages and stain the conjunctiva. This may follow a conjunctival bleed ,trauma or surgery. Here we are making a wrong diagnosis of jaundice when there is no true elevation of bilirubin in blood. Another situation where one eye is only stained is an artificial eye. Here we ll go wrong as a real case of jaundice being missed.In this case we asked the patient to look down keeping the upper lid elevated. Both side upper sclera yellow.

Same way interpretation of yellow urine.Discoloration of urine may be misinterpreted Consider possibility of food or drug causing discoloration,Consider concentrated urine.Rarely hematuria or hemoglobinuria may be wrongly interpreted as jaundice.

2.Second step.Try to interpret four items together.Check the color of  urine , faeces, see whether towel or dress is stained by sweat and secretions.

There can be different situations based on this.Here consider the bilirubin metabolism.If there is discoloration of eyes and body but urine not stained,  accumulated is  unconjugated bilrubin . Here stools will be brown as the stercobilinogen content is normal or high.
If eyes are stained ,urine stained with or without pale stools and stained dress the problem is beyond conjugation.
Our analysis is just like neurological case approach.First we are trying to pinpoint where is the problem and second step ,what is the nature of pathology.For one "anatomical" localised problem pathology can be of different types depending on many factors.So this step basically help to say whether the problem is before or after conjugation.

If the problem is before conjugation    

ie predominant unconjugated bilirubin problem can again be of two types. 
a.increased level of heme which the conjugation system is not able to tackle.This system can compensate eight times and only when this capacity is exceeded bilirubin level goes up. Classical example of this group is hemolysis of any sort. The compensation is the reason hemolytic patients presents usually with pallor and spleen only and no jaundice even though we consider this triad as supporting hemolysis.If the liver is otherwise damged or some other factor add to the burden of conjugation jaundice occur
b.Normal heme load but the conjugation system is not able to tackle the load.This can occur when there is a problem with the receptar /acceptar protein or transport inside the cell/ligandin which takes bilirubin for conjugation. Classical condition is gilbert syndrome.

If the problem is beyond the level of conjugation

It can be at three levels

a.the first step is delivery of conjugated bilrubin from hepatocytes to the canaliculi.This step is unique as in this entity direct bilirubin goes high in blood but no other evidence of biliary stasis ie other chemicals excreted through bile like cholesterol bile salt and bile acids not elevated in blood.Dubin jhonson syndrome is the classicl example.Most useful question is  "is there itching?"  .If itching is there  it is not Dubin jhonson syndrome.

b.Intrahepatic bile canaliculi.Imagine the gap between two hepatocytes.They can get blocked with the situation of any swelling of hepatocytes.This ll be there in almost all of hepatic parenchymal injuries which happens either due to infection,toxins,metabolic problems etc.when the pathology inside the cells clears the obstruction also clears off.This is the reason for transient obstruction in most of the parenchymal disorders. Many of these canaliculi joins and finally they form right and left hepatic ducts.Hallmark of this situation is cell involvement and so functional derangement of liver is most likely when the direct bilirubin rise in this case.eg low plasma albumin,low coagulation factors leading to bleeding manifestations and in severe cases features of hepatic encephalopathy.

c.obstruction due to exta hepatic biliary system.Main feature of these area are the ducts are lined by smooth muscles and they can contract. So it can lead to colicky pain.So this is  very useful clinical point.One more point is functional derangement of liver is late in this group.

Entities in pediatric age group are biliary  stones,choledochal cyst and in young infant all grades of biliary attresia.

3.Step Three
With the above analysis we localised the problem anatomically. 
Now we ll ask what is the pathology?
.Patholgoy for any of the above entities can be different at different levels. 
eg:in the above case if history is reliable she must be having an acquired problem after the conjugation. It is difficult to pinpoint whether it is intrahepatic or extrahepatic problem from the history.   History does not support functional derangement.At the same time there is no colicky pain or intermittent worsening. So in the anatomical localisation we cant differentiate between the three possibilities at this stage. 
Pahological basis-  It is unlikely to be due to infection.There is no history of drugs or toxins. One other entity which can occur without fever is auto immune hepatitis .But history did nt support.Family history did nt support a metabolic problem which again is one of the entities to be considered.
One point we forgot to mention we did nt consider malignancies in this case.Remember focal pathologies like abscess,parasitic cyst,local malformations or abscess wont lead to jaundice because rest of the normally functioning live tissue will tackle the bilirubin. This can rarely happen if they encroach on to the porta hepatis.

General Examination 

She was not sick .Her vitals stable.Pulse 84/mt  and volume was normal.BP 96/66 mms of Hg
Weight 16.5 kg expected 20 ie  83 percent.Height 108 expected 112, parameters almost normal.

Eyes yellow,

No pallor,NO  congestion of palpebra,No bleed
No KF ring,No evidence of Vitamin A deficiency
No cateract, No xanthelasma palpebrum
Nails normal, no clubbing ,no other discoloratin.
No pedal odema.
No palmar erythema,dupetrens contracture.Mild pigmentation of knuckles.did nt seem significant ,she was dark in complexion.
No scrach marks, bleeds or rashes on the skin.
No spider naevi,No gynecomastia,Flapping tremor could not be elicited.
No significant lymph node enlargement.
Thyroid was normal.

Discussion at the end of General examination 

There were no evidence of decompensation.
What we were looking for at this stage is to get any clue which ll help us to move forward from the above analysis.If there was any features of decompensation like odema ,bleeding manifestations we could have argued for a parenchymal pathology.

One thing is sure. It is unlikely due to an acute infection. Acute infections like hepatitis A,E and lepto usually follow a course of maximum problems within few weeks. Same way rare situations of enteric fever,malaria,ricketsiels ,dengue are out. 

But few infections can still present in a scenario like this evolving over weeks, Classical one is hepatitis C , infectious mononeucleosis ,toxoplasma.But many features almost argue against these possibilities also. eg IMN without any lymph node ,No rash , normal throat no fever almost rules out 

So possibility of other entities which we discussed were to be looked for.

Clues towards auto immune and metabolic liver disorders.

Here no rash, no thyroid enlargement,joints normal , no rashes.

No KF ring.(This was checked by an opthalmologist ,did a slit lamp examinationa and  ruled out KF ring and cateract)

So did we move forward in the above analysis?   Not much.

Gastrointestinal system examination 

Lips, gums, oral mucosa ,tongue and throat normal.

Abdomen examination showed normal skin,no dilated veins,Normal umbilicus.
Minimal distention upper aspect of abdomen.No visible mass
Liver was palpable five cms in the right midclavicular line,eight cms in the epigastrium,span 14cms..Firm in consistency sharp margins,surface smooth.
Spleen six cms firm
No free fluid
No other mass palpable.
No bruit over abdomen.
Other systems within normal limits 

Discussion at the end of system examination
In the inspection of  abdomen in every case of cholestasis spend some time on inspection. Gall bladder is more visible than palpable. This is most common error made and choledochal cyst  missed many times.
In the inspection look for dilated veins and assess the direction of flow.Importance in this situation is caput medusa occur only if the portal obstruction is at the level of liver.Remember the umbilical vein which joins the left branch of hepatic vein.
At the end of GIT examinations we have more important findings which helps. Most important one is the consistency of liver.Even though the history was short firm liver argues that the pathology must be of long duration.
Presence of spleen this size and firm also argues long duration problem. It narrows down the possibilties 
a.Portal hypertension
b.Enlargement of spleen as part of basic illness.Eg.Autoimmune, malaria etc.both entities are unlikely in this case.
So at the end of examination,possibility of chronic liver disease with portal hypertension is likely.
What is the reason for the Chronic liver disease 

1. Is it chronic infection like hepatitis C or B
2. Is it metabolic liver disorder if so which one. 
3. Is it auto immune liver disease

No markers of auto immune nature. No features to support metabolic liver disease .
KF ring is not there, pigmentation does nt seems significant enough to support hemochromatosis. Wilson still can t be ruled out as family history may not be traceable,KF ring occur in 20% cases of hepatic wilson
Chronic infections of hepatitis C can not be ruled out clinically.

investigations

Discussion at the end of investigation.
Could we narrow down the possibilities. One thing confirmed. There is functional derangement which suggests parenchymal liver problem.
Did the investigation help to pinpoint the problem
No. 
Viral markers all negative. So our possibility of hepatitis B,C are ruled out.
Auto immune markers all negative
Metabolic liver diseases also .none of the investigations supported ,common disorders like wilson,hemochromatosis, variants of thyrosinemia

Now what to do ?

Discussion.

Here is the importance of going back to the investigations once again

There are few points which we may not notice in the investigations but ,they are strong clues for diagnosis.

Points which we rarely use,  but very helpful

1. How many times the transaminase elevated.(always do serial measurements)
2. OT/PT ratio
3. Look at the alkaline phosphatase is it unusually low or high
4. Calculate ratio of alkaline phosphatase and GGT

In our case there are few hidden points in the lab parameters.

Look at the OT PT ratio  OT is more than PT

Look at the alkaline phosphatase. It is low

A/G reversal is there 

Out of this in a child the first two investigations strongly argue for the possibility of wilsons disease

But you may argue  that  KF ring is negative and Ceruloplasmin is normal, "cant we rule out wilson?
No Lesson in this case is "common things always common". 
Investigations may mislead you 

we should rule out wilson.

We are planning to send for Challenge with Pencillamin and Liver biopsy next 
i ll update. 
(thanks to Dr.Mohankumar for allowing me to discuss this case. Case belong to P2 unit)