Comments, accounts, and speculations from an English Physician - now retired from practice. I try to realize the principle that opinions should derive from the analysis of demonstrable information, and should evolve if the information changes. kata phusin is classical Greek, meaning "according to natural reality". All original material is subject to Copyright.
Tuesday, October 27, 2009
The Endgame.
Monday, October 26, 2009
The DROLLS 1-3
Saturday, October 24, 2009
Liver Failure - Last Words [ for now ... ]
There exists no reliable system of artificial liver support, despite a half century of expensive research.
There are kidney machines, heart machines, lung machines; there are well established methods to manage loss of intestines, pancreas, endocrine glands, skin, even reproductive organs.
There is no liver machine, and less radical management of liver failure is reactive. We lack the fundamental understanding of liver function necessary for confident, precise management. We have no medical means to reactivate brain and kidney function in liver failure; only liver recovery or transplant does that.
Livers for transplant are hard to obtain. In liver failure the need is urgent: the patient will die in a few days without the transplant. Perfusion techniques mean a liver taken for transplant can now be kept in reasonable condition for a day or two, buying time to bring liver and patient together, in a prepared theatre, with experienced staff. Even so, the opportunities for transplant in liver failure are few. There is no prospect of a 'liver bank', like a blood bank.
In all surgery the best results are from routine, planned procedures. Liver transplantation is major surgery demanding specialised facilities and meticulous preparation.
Animal livers have not proved useful. They cannot be transplanted. In artificial systems they produce plasma for the animal species of origin, which is likely to have serious differences from human plasma.
Liver failure is an unsolved clinical problem. We may appreciate the magnitude and complexity of the abnormalities in liver failure, but so far there is no full understanding of what happens when the liver goes down. Without that strategic understanding management has to be based on trial and error, experience, even guesswork.
Liver medicine awaits a breakthrough in research into the basic physiology of the liver.
Thursday, October 22, 2009
Liver, Brain and Kidney
In my last posting but one I described the clinical features of liver failure. It is interesting that many problems in the management of liver failure are caused by the secondary failure of other organs, especially the brain and kidney. The direct consequences of liver failure - jaundice, blood clotting defects, low blood glucose and low body temperature - are less threatening or are easily treated.
Secondary brain and kidney failure occur together, though one may more severe. If the liver goes down it takes brain and kidney down with it.
Perhaps brain and kidney functions are impaired by the same abnormality, caused by loss of liver function.
If liver function recovers, naturally or after transplant, brain and kidney recover too. The problems are functional, not structural.
I have seen a woman in liver coma for five days recover consciousness in less than twelve hours after a successful liver transplant.
What do brain and kidney have in common? How might liver, brain and kidney interact?
Liver function is central to these questions: kidney failure from other causes does not affect liver or brain function; similarly, coma from other causes does not affect liver or kidney.
High blood flow is a common feature of these three organs. Each takes about a quarter of cardiac output at rest - over a litre per minute in each case. Reduced blood flow may be a factor in the secondary failure of the kidney, but not for the brain.
Brain and kidney also share a dependency on the sodium-potassium pumps in their cell membranes. These produce the chemical and osmotic gradients fundamental to kidney function, and the electrical potentials on which the brain depends.
The conventional wisdom is that liver failure is an intoxication, Substances accumulate in the blood which poison brain and kidney.
Ammonia is the traditional culprit. The problem is that clinical severity does not correlate with blood ammonium values, and washing out ammonium by dialysis does not improve the patient.
The ammonium ion is physically similar to the potassium ion: it is conceivable that ammonium could interfere with sodium-potassium pumps.
There is a long list of other candidate toxins, including methionine and tyrosine or derivatives, diazepam-like substances, and bacterial endotoxins. The same problems apply: poor correlation of biochemical values and clinical state, and failure to improve on dialysis.
These objections weaken if the toxin binds to plasma proteins, or is itself a protein or other macromolecule. But exchange transfusion is no benefit either.
The intoxication hypothesis is strengthened by the undoubted improvement after emptying the colon: patients in stupor or early coma may be aroused by purging or enema. 'Bowel sterilisation' using antibiotics may also be beneficial. Unfortunately these manoeuvres fail if the liver failure is severe.
[A doctor prescribing an enema for a patient in liver coma should do it himself.]
Deficiency is the alternative to intoxication. The liver produces substances essential for brain and kidney function: loss of these essentials causes the secondary organ failures.
Glucose is an obvious example. Reduced blood glucose content will certainly impair and eventually damage the brain, but most patients in liver coma have adequate blood glucose, naturally or by infusion.
The rapid start-up of brain and kidney after transplant does suggest the restoration of something vital for brain and kidney cell function, either a substrate or an activator of a metabolic process.
Poor activity of membrane sodium-potassium pumps can be demonstrated in white blood cells from patients in liver failure. Incubating the cells in normal plasma rapidly restores full activity.
Such depressed pump activity resembles the effect of digoxin on normal cells. Patients in liver failure do not show the ECG changes familiar after digoxin dosage.
But, it is legitimate to ask, why do membrane sodium-potassium pumps have a receptor for digoxin? The same question asked of the brain and morphine led to the discovery of endorphins.
Digoxin and bile acids share the unusual 5-beta steroid nucleus. So far as I know, this type of steroid is produced only by the liver in humans. Bile acids accumulate in the blood if the bile duct is obstructed. They cause intense itching, and may affect the ECG, but brain and kidney functions are maintained.
So this is my hypothesis. The liver produces a regulating activator of the sodium-potassium pumping enzymes in cell membranes, especially in brain and kidney. Perhaps other ion transporting enzymes are similarly regulated. Function of these enzymes is impaired if supply of the liver activator fails, with consequent encephalopathy and nephropathy.
The activator may be a 5-beta steroid molecule, similar to a bile acid. It may be short lived in the body, so constant synthesis is necessary. The activator binds to the digoxin receptor on the enzyme, and increases its activity. Digoxin binds but does not activate, and blocks access of the activator.
Cerebral oedema is a lethal complication of liver coma. It must happen because the pumping of salt and water out of brain cells has collapsed. This is a hint that membrane pumps are failing, but of course other causes must be considered.
And. of course, the putative activator might not be a 5-beta steroid, but some other substance produced by the liver, maybe a peptide, maybe an active vitamin such as adenosyl-cobalamin, or something else entirely.
May be it is another metabolic pathway which is activated, such as ATP production. Ion pumps need ATP.
I have studied liver failure for many years. I have seen theories and treatments come and go. I perceive that there is a fatigue in liver research at present, especially in the mechanisms and management of liver failure. I suspect the subject needs a breakthrough in understanding of liver function, especially its interactions with other organs.
If I had a research facility, my priority would be liver-kidney interactions - much easier to study than the liver-brain axis. Membrane ion pumps would be my first focus.
Monday, October 19, 2009
The Death of Stephen Gately
What can reliably be concluded about the cause of death of Stephen Gately? Sudden death does occur in apparently fit 33 year old men, but the list of diseases which can do this is short.
Conditions which might cause sudden death in a young man without previous diagnosis include:
- aortic coarctation;
- hypertrophic cardiomyopathy;
- aortic valve stenosis;
- coronary thrombosis;
- pulmonary embolism;
- subarachnoid haemorrhage.
All these would be identified with confidence at necropsy.
Some infections can rarely cause acute death - death within hours of onset. Two might be listed:
- meningococcal septicaemia;
- influenzal pneumonia.
These have a notoriety in this respect, but of course other infections might just do it.
A patient would feel ill, and raise alarm, probably even if sedated.
The authorities have reported that Stephen Gately was found in a kneeling position by a sofa, his head on a pillow. He had vomited, but had not inhaled vomit. At necropsy he had pulmonary oedema.
Pulmonary oedema is fluid accumulation in the tissues and alveoli of the lungs. It can be rapidly fatal if untreated. An erect posture relieves the severe breathing difficulties of pulmonary oedema, so his position when found is consistent.
Pulmonary oedema is not the same as fluid obstructing airflow in the trachea and bronchi, as would be found if vomit were inhaled, or in drowning.
The fluid in pulmonary oedema comes from the blood, not from outside.
I can imagine him asleep on the sofa, awakening in severe respiratory distress, weakened and confused by lack of oxygen, and managing to struggle to a kneeling position before final collapse and death.
The problem is that pulmonary oedema is not a complete diagnosis. In Britain a death certificate citing pulmonary oedema alone would be returned by the registrar. Pulmonary oedema is due to a primary condition, most commonly affecting the left ventricle of the heart and causing it to fail.
The first four conditions listed above could do this, but none is mentioned by the authorities. Perhaps more information will be released eventually.
Speculation is always dangerous, especially where there is celebrity and controversy. However I can think of one further cause of sudden death from pulmonary oedema, and that is the drug Ecstacy, MDMA.
Acute heart failure and pulmonary oedema are recognised complications of high doses of MDMA. This cause of death might not be evident at necropsy.
I understand samples are in the toxicology laboratory, so this hypothesis will be tested.
In the meantime we can only reflect again on the fragility of life, especially when acutely challenged, and mourn the death of a man in his prime.
Friday, October 16, 2009
Cirrhosis: Foul and Fatal
Cirrhosis: cirrhosis of the liver. It is an untreatable, lethal disease. Any study of the prognosis of cirrhosis in Britain is likely to find that, from the time of diagnosis, half are dead within one year, and very few will survive five years. Many cancers have similar prognoses.
The incidence of liver cirrhosis is increasing, especially among women. Epidemic alcoholism is the most important cause, but demographic change is increasing the number of cases of imported liver disease, notably chronic hepatitis B and C.
Cirrhosis should be an active subject of public and political concern, but there is lack of understanding about the disease, and a popular tendency to dismiss warnings about alcohol.
Make no mistake. Cirrhosis is deadly, and a foul way to go. The occasional patient can be rescued by liver transplant, but the opportunities for this dramatic intervention are few.
Cirrhosis is a process which destroys normal liver structure and function. Sustained or repeated injury to the liver lights up a chronic inflammation, which progressively damages and destroys liver cells. Fibrous scars develop in the liver substance. The injury also damages the liver's normal regeneration and repair mechanisms, so that abnormal nodules of liver cells begin to replace surviving normal liver tissues.
These nodules fail to link properly into liver blood and bile systems: the nodular cells cannot provide normal liver function.
Eventually the smooth normal liver is replaced by a nodular scarred mass, essentially a fibrous conglomerate of benign liver tumours.
Cirrhosis, once started, tends to progress remorselessly: stopping drinking has little effect.
The blood supply of the liver is unusual. Blood coming from the intestines, spleen and pancreas is intercepted by the liver, for processing before release into the general circulation. The veins from intestines, spleen and the pancreas join to form the portal vein, which then branches into the liver. There is an arterial supply, the hepatic artery, but this is relatively small.
Total blood flow through the liver at rest is about one quarter of cardiac output, approximately equal to blood flow through the brain.
What is the function of the liver? This was a favourite question to students, and few indeed were the occasions when the answer was satisfactory.
The liver is a gland secreting two fluids.
Bile is the first: a liquid secreted through the bile duct into the duodenum. It is the pathway for the excretion of bilirubin, a breakdown product of haemoglobin. Bile also assists digestion, providing the detergent bile acids, phospholipids and cholesterol needed, especially for the absorption of fats.
Blood plasma is the second secretion of the liver, and by far the most important.
Blood is the product of three organs: bone marrow and lymphatics supply the cellular components; the kidney regulates water and mineral balance; the liver synthesises and controls the complex array of organic molecules which make up the plasma - glucose, albumin, blood clotting factors and so on.
The liver is the custodian of the constancy of the internal environment, the condition for free life, independent of the environment.
If the body is an engine, the liver is the carburettor.
Liver function ensures that the blood has a constant composition: the concentrations of plasma components are controlled within strict limits. It synthesises as necessary, stores and releases glucose and other nutrients, and removes wastes and foreign substances.
Liver function maintains the plasma volume, by regulating the synthesis and plasma concentration of albumin.
The liver is the main source of body heat at rest: its intense metabolism produces heat. It is notably hot to the touch, and blood leaving the liver is the hottest in the body, commonly at least one centigrade degree above the body temperature.
The liver has defence functions too - trapping and destroying bacteria and foreign materials in the blood from the intestines.
Liver, kidney and bone marrow function must be closely co-ordinated. These interactions are poorly understood, but their failure in liver disease has important clinical consequences.
The liver has a huge functional reserve: probably 90% of liver function may be lost before clinical problems begin.
The syndrome of liver failure has three main parts.
Jaundice is the first: accumulation of bilirubin in the blood. This is disfiguring, but does little to impair health otherwise.
The second is nephropathy: impaired kidney function. The patient cannot excrete salt and water adequately. Daily urine volume falls, and sodium excretion may be less than a tenth of normal. The normal urinary excess of sodium over potassium is reversed.
Oedema develops, especially of the lower parts - feet, legs, abdomen. There is likely also to be fluid accumulating in the abdomen - ascites.
This retention of water dilutes the plasma: thus the concentration of albumin falls, but the total body albumin pool is normal or even increased.
In some way the liver drives kidney water and salt excretion. The mechanism of this interaction is not clear.
The third is encephalopathy - disturbance of brain function. In the early stages this causes apathy, loss or reversal of diurnal rhythms, loss of social inhibitions, poor spatial discrimination, and other neuro-psychiatric changes. 'Flapping tremor' is a transient, abrupt loss of posture of the out-stretched hands, with instant recovery. It occurs in other metabolic brain diseases.
Stupor leading to coma is the final state of liver failure. Once established, coma is difficult to reverse and the prognosis is poor.
Fetor is common in liver failure - an unpleasant smell to the breath, like bad meat. It is caused by the excretion of methylated sulphur compounds into the inspired air.
Liver failure is one mode of death in cirrhosis. There are at least two more.
Blood flow through a cirrhotic liver is impeded. Pressure increases in the portal vein, and venous pathways bypassing the liver open up. Eventually varicose veins develop, notably in the lower oesophagus, but also in the rectum and round the umbilicus. These are points where the portal and systemic circulations meet.
Oesophageal varices are large, thin-walled veins, carrying a big flow of blood. They rupture easily, causing severe bleeding into the oesophagus, and so massive vomiting of blood. This dangerous catastrophe is difficult to manage. Varices can be blocked by endoscopic injections of sclerosing substances, when they are not bleeding. Occasionally other interventions are possible.
No one who has witnessed a patient dying in a bed-full of blood will ever doubt the dreadful consequences of cirrhosis.
Finally, malignancy may develop in a cirrhotic liver. Usually a sudden deterioration raises suspicion. Sometimes a blood test can confirm the diagnosis, but the diagnosis may be made only at post-mortem. Malignant change is untreatable and likely to be rapidly fatal.
Never risk cirrhosis. Heed warnings about safe drinking; immunise against hepatitis; practise safe sex - hepatitis is transmitted venereally.
Cirrhosis is as lethal as cancer.
Sunday, October 11, 2009
Artemis Rampant
The season of fashion shows is here. Haute Couture is strutting its stuff. And bizarre stuff it often is: do some of these apparitions appear anywhere but on the catwalk?
I gaze in disbelief at the pictures in the weekend supplements. Is it because I'm male, or because I'm 70+, or maybe both?
Being male may be a factor. These beanstalk models and their fantasy outfits are not meant to be attractive to men; they are, if anything, anti-sexy, male-repellent.
The models project challenging female self-sufficiency: feminist, not feminine. Their gait and manner is arrogant, unsmiling, unappealing. The clothes neither flatter nor enhance a female figure; on the contrary, they flatten and conceal any curves the model may have. A fashion designer said recently on television that his clothes did not hang well on a woman more than size 12.
The whole appearance is designed to impress and dominate, especially other women.
These are the votaries of Artemis: Aphrodite has no place here.
Catwalk models may be admired role models for anorexics, but I suspect these two groups of underweight woman differ in psychology.
Those models do not show the classic features of anorexia nervosa. Self confidence is the opposite of the 'daddy's little girl' posturing of the truly anorexic; charming, manipulative, devious, untruthful, so badly treated by others. Watch the famous interview by Lady Diana - the adult anorexic personality on display.
Severely affected anorexics starve themselves into extreme body wasting, but the breasts are often surprisingly preserved. No doubt catwalk models starve themselves too, and smoke cigarettes rather than eat, but I suspect they are often naturally tall, skinny women, with poorly developed female body contours.
Anorexia nervosa is a flight from sex and motherhood, a wish to remain juvenile, a phobia of fat, perceived as a symbol of sexual maturity. It is aberrant development of the maternal instinct; turning inward to love of the immature self.
Catwalk models suppress and disguise their normal sexuality.
So who designs these fantasy outfits for for these anti-feminine women? Well, are high proportion are homosexual men.
Draw your own conclusions.
What strange lives these people must lead.
But I suggest there is material for a doctorate thesis in psychology in just one season of these fashion shows.
Thursday, October 08, 2009
These Stubborn Islanders
I prize my first edition copy of Chester Wilmot's book 'The Struggle for Europe', published 1952. It is a classic history of the allied invasion of Normandy and the subsequent campaigns which ended with the defeat of Nazi Germany. Wilmot was an Australian who reported for the BBC. He saw the campaign in the west from its beginning: he flew in on D-Day in a glider. He was present at its end, at the surrender of the German High Command on the Lüneberg Heath.
He was killed in 1954, in the first BOAC comet disaster.
He wrote this about the British reaction to defeat in 1940, and Hitler's misjudgement of the British mood - a misjudgement which proved critical for Germany's eventual defeat.
>>
Once the first shock of the disaster in Flanders had passed, the people of Britain, with their strange capacity for seeing victory in defeat, drew encouragement from Dunkirk.
The miraculous escape of 225,000 British troops from what had appeared to be certain destruction or capture came to be regarded as a divine deliverance which gave men and women throughout the land new faith in themselves and their destiny.
This was not the first time that a continental despot had stood on the shores of France and hurled threats across the channel. Time and again in the past 400 years England had fought to prevent the domination of Europe by a single power. Hitler was now faced with the same British stubbornness that had baulked Philip of Spain, Louis XIV, Napoleon and Kaiser Wilhelm II.
When Hitler looked across the Channel from Cap Gris Nez in June, he saw only Britain's present material weakness; he did not appreciate the strength and courage her people drew instinctively from the past.
Ignoring the warning of history, Hitler clung to the hope of another 'Munich', or at least an 'Amiens', but he was extravagantly optimistic in thinking that the traditional Balance-of-Power could be jettisoned by any British statesman in the summer of 1940, not least by the descendent of its most renowned exponent, John Churchill, first Duke of Marlborough."
<<
I understand that on Cap Gris Nez that day, a general reminded Hitler of the words of one of Napoleon's marshals, as they stood on the same spot under similar circumstances:
"There are bitter weeds in England".
We now know now that Hitler's first taste of the bitterness of defeat was delivered by Hurricanes and Spitfires: each carrying eight machine guns, and powered by the Rolls Royce Merlin engine.
In the light of this recent history, how should we Britons today respond to the unfolding conspiracy to entrap us in a European super-state, under German-French hegemony? Do we consent to most of our policies being decided by unelected Eurocrats? Is our elected Westminster parliament still to be the 'sole power under God' in this United Kingdom? Do we submit to a future as second-class offshore islanders?
Do we, at last, abandon our Balance-of-Power strategy?
When they say Tony Blair is the best man to be our new, unelected, President, are we expected to applaud? Will they tell us if the new President will have precedent over our Prime Minister - and what is the status of the Queen in all this?
When Edward Heath took Britain into the Common Market [as then it was called], assurances came from all sides that this was not the first step towards our assimilation in a United States of Europe: it was a commercial union, not a political movement. On this assurance I voted 'yes' in the subsequent referendum. How badly we were deceived became apparent as the years passed, and successive governments signed up to increasingly political European treaties.
It is reported that now 70% of the time of parliament is spent passing rules and regulations from Brussels into British law.
It is true that European integration has made war in Europe unthinkable, and that is a huge advance. I believe that for a thousand years until my generation no Frenchman had lived to 70 without seeing his country invaded by Germany.
This most welcome development was already achieved in the Common Market: nothing is added by the ensuing drive for political integration.
I shall never agree the Lisbon Treaty is valid until it has been approved by a free vote of the British people. I believe this opinion is consistent with traditional British values and strategies.
The promised referendum is the bitter weed in England which the Eurocracy has conspired to kill.
Wednesday, October 07, 2009
Fascism in the 21st. Century
'Fascist' - it has become a term of abuse, intended to induce guilt, a contemptuous dismissal of opinions which the speaker doesn't like, but can't rebut convincingly.
What is the correct use of this word?
Fascisti was the name of Mussolini's political party in Italy, 1922-1943. The Latin fasces means a bundle, and was used for the axe bundled in rods which was the symbol of a Roman magistrate. Fascism came to be the group name for similar political movements and governments in other European countries in the 20's and 30's; in Germany, Spain, Croatia and Romania. There was a British Fascist Party in the 1930's, but it never achieved mass support.
Italy had been a single state only for a half-century when the fascist movement began: the bound bundle of rods had a significance we easily overlook.
Paranoid nationalism is a key feature of fascism. The nation is threatened or unjustly treated by enemies within and without. Militarism is one response. I remember seeing a faded slogan painted on a house wall in Italy:
Il Credo Del Fascismo E L'Eroismo.
Another response is oppression of those perceived to be hostile, or secretly plotting against the nation.
Judeophobia is intrinsic to fascism.
Fascist patriotism demands submission to the state as embodied in the fascist party and its leader. Democracy is a danger and a distraction: the party, by definition, knows best, and will be violent towards any that demur.
Fascist parties typically include paramilitaries: brownshirts, blackshirts and so on: street brawlers marching, drinking, singing, and fighting opponents. In Germany they became official private armies - the SA and SS.
Idolatry of The leader is perhaps the distinctive feature of fascism: Der Führer, Il Duce, El Caudillo. A leader endowed with mystical wisdom and power, who will lead the Nation to salvation. Remember those grainy films of huge crowds, enraptured to hysteria by the sight and words of the Führer? We may gaze in disbelief now, but it happened.
Fascist economic policies are socialist; a command economy, driven in part by preparations for war. "Far right" is an absurd name for fascist parties.
But fierce anti-communism is universal in fascism, despite the close similarities between the two. Stalin, Mao, Kim Il Sung: these were fascist leaders in most respects, except title.
In Ireland Sinn Fein - 'ourselves alone' - is arguably fascist, except it never had a great leader. But it had dangerous paramilitaries, and its founder was notoriously judeophobe.
I perceive very little native fascism in Europe today. There are nationalist parties of varying popularity, but none has the intensity, paranoia and idolatry of fascism.
Yet the evil that Fascists did lives after them. The shame and guilt of the fascist era corrodes the self-confidence of modern Europeans, inhibiting action if any echo of fascism is perceived.
Fascism enjoyed mass support for a time: from this memory comes the suspicion of democracy so prominent in the godfathers of the European Union.
Today the shadow of fascism taints even the benign nationalism needed to counter the unelected Eurocracy in its quest for Napoleonic powers.
Real Fascism today is mostly religious.
Islam, for example, is a hierocracy with strong fascist features: paranoia, warrier-worship, submission, crudely socialist economics, judeophobia, and idolatry of leaders who claim to be agents of the Greatest Leader of all. It also has paramilitaries; young men [and some women] persuaded that suicidal violence is the sure way into God's great Playboy Mansion in the sky.
In the 1930's and 40's many muslims made common cause with European fascists.
So it is bizarre to see muslims demonstrating and brawling under the banner of "Unite Against Fascism". It is equally bizarre to see communists making common cause with them.
The great struggle of the 21st. century is between those who pray to God the Father, and those who prostrate to God the Führer.
Friday, October 02, 2009
Magna est Veritas
I suppose, in these days, few have heard of Coventry Patmore, and fewer still value his poetry. His Victorian style is unfashionable. Mannered archaic usage and lapses into sentimentality were popular in his time, but date him now.
At his best he achieves greatness, recognised by four entries in the New Oxford Book of English Verse.
Here is one I shall never forget. Of course 'reality' is my reading of 'truth', and likely to differ from catholic Patmore's.
It captures the sense of futility to which 70-year olds are prone.
Magna est Veritas
Here, in this little bay,
Full of tumultuous life and great repose,
Where, twice a day,
The purposeless, glad ocean comes and goes,
Under high cliffs, and far from the huge town,
I sit me down.
For want of me the world's course will not fail;
When all its work is done, the lie shall rot;
The truth is great, and shall prevail,
When none cares whether it prevail or not.