Epidemiology and Aetiology Major health problem – 300 million carriers Incubation 1 - 4 mths Parenteral transmission – sexual, IV, perinatal 0.5% of UK population are carriers, but this is as much as 10-15% in some countries in the developing world. in some far eastern countries, 1/3 of people are carriers. E.g. in Yemen ¼ of the population have hep B PresentationAcute Hepatitis B
So you're sitting in a bus when you see a baby smile sunnily and gurgle at his mother. Your automatic response? You smile too. You're jogging in the park, when you see a guy trip over his shoelaces and fall while running. Your knee jerk reaction? You wince. Even though you're completely fine and unscathed yourself. Or, to give a more dramatic example; you're watching Titanic for the umpteenth time and as you witness Jack and Rose's final moments together, you automatically reach for a tissue and wipe your tears in whole hearted sympathy ( and maybe blow your nose loudly, if you're an unattractive crier like yours truly).
And here the question arises- why? Why do we experience the above mentioned responses to situations that have nothing to do with us directly? As mere passive observers, what makes us respond at gut level to someone else's happiness or pain, delight or excitement, disgust or fear? In other words, where is this instinctive response to other people's feelings and actions that we call empathy coming from?
Science believes it may have discovered the answer- mirror neurons.
In the early 1990s, a group of scientists (I won't bore you with the details of who, when and where) were performing experiments on a bunch of macaque monkeys, using electrodes attached to their brains. Quite by accident, it was discovered that when the monkey saw a scientist holding up a peanut, it fired off the same motor neurons in its brain that would fire when the monkey held up a peanut itself. And that wasn't all. Interestingly, they also found that these motor neurons were very specific in their actions. A mirror neuron that fired when the monkey grasped a peanut would also fire only when the experimenter grasped a peanut, while a neuron that fired when the monkey put a peanut in its mouth would also fire only when the experimenter put a peanut in his own mouth. These motor neurons came to be dubbed as 'mirror neurons'.
It was a small leap from monkeys to humans. And with the discovery of a similar, if not identical mirror neuron system in humans, the studies, hypotheses and theories continue to build. The strange thing is that mirror neurons seem specially designed to respond to actions with clear goals- whether these actions reach us through sight, sound, smell etc, it doesn't matter. A quick example- the same mirror neurons will fire when we hop on one leg, see someone hopping, hear someone hopping or hear or read the word 'hop'. But they will NOT respond to meaningless gestures, random or pointless sounds etc. Instead they may well be understanding the intentions behind the related action. This has led to a very important hypothesis- the 'action understanding' ability of mirror neurons.
Before the discovery of mirror neurons, scientists believed our ability to understand each other, to interpret and respond to another's feeling or actions was the result of a logical thought process and deduction. However, if this 'action understanding' hypothesis is proved right, then it would mean that we respond to each other by feeling, instead of thinking. For instance, if someone smiles at you, it automatically fires up your mirror neurons for smiling. They 'understand the action' and induce the same sensation within you that is associated with smiling. You don't have to think about what the other person intends by this gesture. Your smile flows thoughtlessly and effortlessly in return.
Which brings us to yet another important curve- if mirror neurons are helping us to decode facial expressions and actions, then it stands to reason that those gifted people who are better at such complex social interpretations must be having a more active mirror neuron system.(Imagine your mom's strained smile coupled with the glint in her eye after you've just thrown a temper tantrum in front of a roomful of people...it promises dire retribution my friends. Trust me.)
Then does this mean that people suffering from disorders such as autism (where social interactions are difficult) have a dysfunctional or less than perfect mirror neuron system in some way?
Some scientists believe it to be so. They call it the 'broken mirror hypothesis', where they claim that malfunctioning mirror neurons may be responsible for an autistic individual's inability to understand the intention behind other people's gestures or expressions. Such people may be able to correctly identify an emotion on someone's face, but they wouldn't understand it's significance. From observing other people, they don't know what it feels like to be sad, angry, surprised or scared.
However, the jury is still out on this one folks. The broken mirror hypothesis has been questioned by others who are still skeptical about the very existence of these wonder neurons, or just how it is that these neurons alone suffered such a developmental hit when the rest of the autistic brain is working just dandy? Other scientists argue that while mirror neurons may help your brain to understand a concept, they may not necessarily ENCODE that concept. For instance, babies understand the meaning behind many actions without having the motor ability to perform them. If this is true, then an autistic person's mirror neurons are perfectly fine...they were just never responsible for his lack of empathy in the first place.
Slightly confused? Curious to find out more about these wunderkinds of the human brain? Join the club. Whether you're an passionate believer in these little fellas with their seemingly magical properties or still skeptical, let me add to your growing interest with one parting shot- since imitation appears to be the primary function of mirror neurons, they might well be partly responsible for our cultural evolution! How, you ask? Well, since culture is passed down from one generation to another through sharing, observation followed by imitation, these neurons are at the forefront of our lifelong learning from those around us. Research has found that mirror neurons kick in at birth, with infants just a few minutes old sticking their tongues out at adults doing the same thing.
So do these mirror neurons embody our humanity? Are they responsible for our ability to put ourselves in another person's shoes, to empathize and communicate our fellow human beings? That has yet to be determined. But after decades of research, one thing is for sure-these strange cells haven't yet ceased to amaze and we definitely haven't seen the last of them. To quote Alice in Wonderland, the tale keeps getting "curiouser and curiouser"!
Anatomy and pathology of the nervous system is understood by directly visualizing it. This is best accomplished by handling the brain (or model of the brain as the case may be) and dissecting or taking it apart for direct examination. The purpose (for the clinician) of understanding neuroanatomy and neurophysiology is to be able to use that knowledge to solve clinical problems. The first step in solving a clinical problem is anatomical localization. So, if one cannot directly inspect the patient's brain, how is this localization accomplished? The "window" to the patient's brain is the neurological examination. The neuro exam is a series of tests and observations that reflects the function of various parts of the brain. If the exam is approached in a systematic and logical fashion that is organized in terms of anatomical levels and systems then the clinician is lead to the anatomical location of the patient's problem.
The registrar's face was taking on a testy look. So enduring was the silence our furtive glances had developed a nystagmic quality. “Galactosaemia” came her peremptory reply. Right on queue the disjointed chorus of ahs and head nods did little to hide our mental whiteboard of differentials being wiped clean. At the time conjugated bilirubinaemia in children only meant one thing: biliary atresia. A fair assumption; we were sitting in one of three specialist centres in the country equipped to treat these patients. Ironically the condition has become the unwieldy yardstick I now measure the incidence of paediatric disease.
Biliary atresia is the most common surgical cause of neonatal jaundice with a reported incidence of 1 in 14-16ooo live births in the West. It is described as a progressive inflammatory obliteration of the extrahapatic bile duct. And Dr Charles West, the founder of Great Ormond Street Hospital, offers an eloquent description of the presenting triad of prolonged jaundice, pale acholic stools and dark yellow urine:
‘Case 18...It was born at full term, though small, apparently healthy. At 3 days however, it began to get yellow and at the end of 3 weeks was very yellow. Her motions at no time after the second day appeared natural on examination, but were white, like cream, and her urine was very high coloured.’
1855 was the year of Dr West's hospital note. An almost universally fatal diagnosis and it would remain so for the next 100 years. The time's primordial classification of biliary atresia afforded children with the 'noncorrectable' type, a complete absence of patent extrahepatic bile duct, an unfortunate label; they were beyond saving. Having discovered the extent of disease at laparatomy, the surgeons would normally close the wound. The venerable Harvardian surgeon, Robert E. Gross saved an enigmatic observation: “In most instances death followed a downhill course…”
K-A-S-A-I read the ward’s board. It was scrawled under half the children's names. I dismissed it as just another devilishly hard acronym to forget. The thought of an eponymous procedure had escaped me and in biliary atresia circles, it's the name everyone should know: Dr Morio Kasai.
Originating from Aomori prefecture, Honshu, Japan, Dr Kasai graduated from the National Tohoku University School of Medicine in 1947. His ascension was rapid, having joined the 2nd department of Surgery as a general surgeon, he would assume the role of Assistant Professor in 1953. The department, under the tenure of Professor Shigetsugu Katsura, shared a healthy interest in research.
1955 was the landmark year. Katsura and Kasai operated on their first case: a 72 day old infant. Due to bleeding at the incised porta hepatis, Katsura is said to have 'placed' the duodenum over the site in order to staunch the flow. She made a spectacular postoperative recovery, the jaundice had faded and there was bile pigment in her stool. During the second case, Katsura elected to join the unopened duodenum to the porta hepatis. Sadly the patient's jaundice did not recover, but the post-mortem conducted by Kasai confirmed the development of a spontaneous internal biliary fistula connecting the internal hepatic ducts to the duodenum. Histological inspection of removed extrahepatic duct showed the existence of microscopic biliary channels, hundreds of microns in diameter. Kasai made a pivotal assertion: the transection of the fibrous cord of the obliterated duct must contain these channels before anastomosis with the jejunal limb Roux-en-Y loop. This would ensure communication between the porta hepatis and the intrahepatic biliary system. The operation, entitled hepatic portoenterostomy, was first performed as a planned procedure for the third case at Tohoku. Bile flow was restored and Kasai published the details of the new technique in the Japanese journal Shujutsu in 1959. However, news of this development did not dawn on the West until 1968 in the Journal of Pediatric Surgery. The success of the operation and its refined iterations were eventually recognized and adopted in the 1970s. The operation was and is not without its dangers. Cholangitis, portal hypertension, malnutrition and hepatopulmonary syndrome are the cardinal complications. While diagnosing and operating early (<8 weeks) are essential to the outcome, antibiotic prophylaxis and nutritional support are invaluable prognostic factors.
Post operatively, the early clearance of jaundice (within 3 months) and absence of liver cirrhosis on biopsy, are promising signs. At UK centres the survival after a successful procedure is 80%. The concurrent development of liver transplantation boosts this percentage to 90%. Among children, biliary atresia is the commonest indication for transplantation; by five years post-Kasai, 45% will have undergone the procedure.
On the 6th December 2008, Dr Kasai passed away. He was 86 years old and had been battling the complications of a stroke he suffered in 1999. His contemporaries and disciples paint a humble and colourful character. A keen skier and mountaineer, Dr Kasai lead the Tohoku University mountain-climbing team to the top of the Nyainquntanglha Mountains, the highest peaks of the Tibetan highlands. It was the first successful expedition of its kind in the world. He carried through this pioneering spirit into his professional life. Paediatric surgery was not a recognized specialty in Japan. By founding and chairing multiple associations including the Japanese Society of Pediatric Surgeons, Dr Kasai gave his specialty and biliary atresia, the attention it deserved.
Despite numerous accolades of international acclaim for his contributions to paediatric surgery, Dr Kasai insisted his department refer to his operation as the hepatic portoenterostomy; the rest of the world paid its originator the respect of calling it the ‘Kasia’. Upon completion of their training, he would give each of his surgeons a hand-written form of the word ‘Soshin’ [simple mind], as he believed a modest surgeon was a good one.
At 5 foot 2, Kasai cut a more diminutive figure one might expect for an Emeritus Professor and Hospital Director of a university hospital. During the course of his lifetime he had developed the procedure and lived to see its fruition. The Kasia remains the gold standard treatment for biliary atresia; it has been the shinning light for what Willis J. Potts called the darkest chapter in paediatric surgery. It earned Dr Kasai an affectionate but apt name among his peers, the small giant.
Miyano T. Morio Kasai, MD, 1922–2008. Pediatr Surg Int. 2009;25(4):307–308.
Garcia A V, Cowles RA, Kato T, Hardy MA. Morio Kasai: a remarkable impact beyond the Kasai procedure. J Pediatr Surg. 2012;47(5):1023–1027.
Mowat AP. Biliary atresia into the 21st century: A historical perspective. Hepatology. 1996;23(6):1693–1695.
Ohi R. A history of the Kasai operation: Hepatic portoenterostomy for biliary atresia. World J Surg. 1988;12(6):871–874.
Ohi R. Morio Kasai, MD 1922-2008. J Pediatr Surg. 2009;44(3):481–482.
Lewis N, Millar A. Biliary atresia. Surg. 2007;25(7):291–294.
This blog post is a reproduction of an article published in the Medical Student Newspaper, April 2014 issue.