HORMONES AND FLUID RETENTION IN CIRRHOSIS
2
1341 immunological susceptibility or persistence of the virus is not clear. The rarer condition of severe myocarditis may proceed rapidly to severe intractable heart failure, resolved only by heart transplantation or death. Whether some cases of congestive cardiomyopathy are the late manifestation of previous viral infection8 remains enigmatic but the possibility provides some further pressure on the physician to turn to an electrocardiogram in infective illness of uncertain nature; and to treat acute cardiac muscle infections with consideration and rest. Anti-inflammatory drugs such as steroid agents have been recommended in the acute illness, but there is evidence of possible harm from such treatment.9 DANGEROUSNESS PSYCHIATRY has moved far in the past 200 years. Its main function is no longer the protection of society from madness but the restoration of health to the mentally ill. Nonetheless, the psychiatrist concentrating on treating the patient has to remind himself continually that society is looking over his shoulder and monitoring his broad responsibilities. The average psychiatrist will break the Hippocratic Oath many times each year, since he has to compromise between what he regards as best for the patient and what society will tolerate. This conflict is shown most clearly at the special hospitals such as Broadmoor or Rampton, where apparently well patients may be detained for years because of their potential risk to society if they are released. There are many types of psychiatric disorder that society is prepared to tolerate, but the line is drawn at those which include the potential to do harm to others. Deluded schizophrenic, overactive manic, and hallucinating alcoholic patients are all accepted provided they do not act aggressively or threaten to do so. The concept of dangerousness has been embraced as a measure of this harmful risk although there is no unified definition to encompass all its aspects. Scott’ defined it as "an unpredictable and untreatable tendency to inflict or risk serious irreversible injury or destruction, or to induce others to do so". Although this definition is pertinent to individuals in the psychiatric context, activities in the South Atlantic show that it can be applied just as well to larger groups, and whether or not it is acceptable is culturally dependent. In a booklet published under the auspices of the Royal College of Psychiatrists the concept and implications of dangerousness are examined comprehensively. Despite its importance the subject has been resistant to objective inquiry, reflected by the fact that the 20 contributors can muster a total of only 138 references. J. R. Hamilton sums up the task of the psychiatrists at Broadmoor in the words "our job is to treat dangerous patients and remove their dangerousness", but all contributors are agreed that they have no way of ensuring that their treatment is effective. J. Gunn emphasises that "predicting who will do things again" is the key aim in assessment but P. McGrath admits that although psychiatrists have a contribution to make they "are no better 8. Cambridge G, MacArthur CGC, Waterson AP, Goodwin JF, Oakley CM. Antibodies to Coxsackie B viruses in congestive cardiomyopathy. Br Heart J 1979; 41: 692 692-96. 9. Kilbourne ED, Wilson CB, Perrier D The induction of gross myocardial lesions by a Coxsackie (pleurodynia) virus and cortisone J Clin Invest 1956; 35: 362-70. 1. Scott PD Assessing dangerousness in criminals. Br J Psychiatry 1977; 131: 127-42. 2 Hamilton JR, Freeman H, eds. Dangerousness psychiatric assessment and management London. Gaskell, for the Royal College of Psychiatrists (available from Headley Brothers Ltd, Queen’s Rd, Ashford, Kent TN24 8HH) 1982 Pp. 121. £4 75. in assessing dangerousness than members of many other disciplines". T. Harding and C. Montandon, in a cross- cultural comparison, found a 57% level of agreement in assessing dangerousness for the case-histories of patients from six countries-a level of prediction that is much better than chance but far too low to be of value in an individual case. The decision whether and when to discharge a patient who has acted dangerously in the past is an exercise in the analysis of risk that would frighten the most accomplished actuary. Most authorities agree that, to ensure that patients who are a danger to society do not leave hospital prematurely, at least two or three times as many patients will be detained unnecessarily. Those who are wrongly detained are deprived of their rights in a way that is unacceptable to the civil libertarians. In the United States several such patients have been judged unconstitutionally detained, and this has led to the release of many mentally ill people against the advice of their clinicians; and follow-up of these patients has shown a much lower incidence of violence than was predicted.3-5 Unfortunately there is no way of predicting when re-offences are likely to arise and a long period of follow-up is necessary because repetition of arson, rape, and homicide may take place many years after release.6,7 Most re-offences occur without any warning and are impossible to prevent by means other than detention. The ethical aspects of dangerousness are discussed by N. Walker in a thoughtful contribution to the symposium that develops a theme of an earlier paper. He emphasises that the decision whether or not to release a mentally abnormal offender is one that appeals to values rather than relies on objective evidence or statistical risk. If detention in hospital may prevent lasting hardship to others; if the original offence was consistent with the patient’s personality and behaviour in hospital; if the circumstances of the original offence still exist; and if no other form of protection other than detention is possible-then it is acceptable to keep the offender in hospital, but only under conditions that are civilised and tolerable. The hazard of relying on value judgments is shown by the later contributions from A. Bothams and D. West, who disagree with the "protectionist" policy and argue for a more generous attitude towards offenders. We are left with an unenviable position because, in Tennent’s words,9 "in predicting rare behaviour there will be more false positives than accurate predictions". Those who are unfortunate enough to be caught amongst the false positives have cause for complaint. Those responsible for the detention and treatment of the apparently dangerous patient need to stress their case, lest the rate of false negatives increase and determine the reaction of society. HORMONES AND FLUID RETENTION IN CIRRHOSIS FLUID retention leading to ascites and peripheral oedema is a common feature of cirrhosis and advancing liver failure. At first it usually responds to salt and water restriction, diuretics, and removal of the cause (for example, by alcohol 3 Steadman HJ, Keveles G. The community adjustment and criminal activity of the Baxtrom patients 1966-70. Am J Psychiatry 1972: 129: 304-10 4 Cocozza JJ, Steadman HJ Some refinements in the measurement and prediction of dangerous behaviour. Am J Psychiatry 1974; 131: 1012-14 5. Thornberry TP, Jacoby JE. The criminally insane in a community follow-up of mentally ill offenders. Chicago. Chicago University Press. 1979 6. Soothill KL, Pope PJ Arson: a 20 year cohort study Med Sci Law 1973, 13: 127-38 7. Soothill KL, Jack A, Gibbens TCN. Rape: a 22-year cohort study Med Sci Law 1976; 16: 62-69 8. Walker N. Dangerous people. Int J Law Psychiatry 1978. 1: 37-49. 9. Tennent TG The dangerous offender. Br J Hosp Med 1971; 5: 269-74.
Transcript of HORMONES AND FLUID RETENTION IN CIRRHOSIS
1341
immunological susceptibility or persistence of the virus is notclear. The rarer condition of severe myocarditis may proceedrapidly to severe intractable heart failure, resolved only byheart transplantation or death. Whether some cases of
congestive cardiomyopathy are the late manifestation of
previous viral infection8 remains enigmatic but the
possibility provides some further pressure on the physician toturn to an electrocardiogram in infective illness of uncertainnature; and to treat acute cardiac muscle infections withconsideration and rest. Anti-inflammatory drugs such assteroid agents have been recommended in the acute illness,but there is evidence of possible harm from such treatment.9
DANGEROUSNESS
PSYCHIATRY has moved far in the past 200 years. Its mainfunction is no longer the protection of society from madnessbut the restoration of health to the mentally ill. Nonetheless,the psychiatrist concentrating on treating the patient has toremind himself continually that society is looking over hisshoulder and monitoring his broad responsibilities. Theaverage psychiatrist will break the Hippocratic Oath manytimes each year, since he has to compromise between what heregards as best for the patient and what society will tolerate.This conflict is shown most clearly at the special hospitalssuch as Broadmoor or Rampton, where apparently wellpatients may be detained for years because of their potentialrisk to society if they are released.There are many types of psychiatric disorder that society is
prepared to tolerate, but the line is drawn at those whichinclude the potential to do harm to others. Deluded
schizophrenic, overactive manic, and hallucinating alcoholicpatients are all accepted provided they do not act aggressivelyor threaten to do so. The concept of dangerousness has beenembraced as a measure of this harmful risk although there isno unified definition to encompass all its aspects. Scott’defined it as "an unpredictable and untreatable tendency toinflict or risk serious irreversible injury or destruction, or toinduce others to do so". Although this definition is pertinentto individuals in the psychiatric context, activities in theSouth Atlantic show that it can be applied just as well to largergroups, and whether or not it is acceptable is culturallydependent.
In a booklet published under the auspices of the RoyalCollege of Psychiatrists the concept and implications ofdangerousness are examined comprehensively. Despite itsimportance the subject has been resistant to objectiveinquiry, reflected by the fact that the 20 contributorscan muster a total of only 138 references.J. R. Hamilton sums up the task of the psychiatrists atBroadmoor in the words "our job is to treat dangerouspatients and remove their dangerousness", but allcontributors are agreed that they have no way of ensuring thattheir treatment is effective. J. Gunn emphasises that
"predicting who will do things again" is the key aim inassessment but P. McGrath admits that althoughpsychiatrists have a contribution to make they "are no better
8. Cambridge G, MacArthur CGC, Waterson AP, Goodwin JF, Oakley CM. Antibodiesto Coxsackie B viruses in congestive cardiomyopathy. Br Heart J 1979; 41: 692692-96.
9. Kilbourne ED, Wilson CB, Perrier D The induction of gross myocardial lesions by aCoxsackie (pleurodynia) virus and cortisone J Clin Invest 1956; 35: 362-70.
1. Scott PD Assessing dangerousness in criminals. Br J Psychiatry 1977; 131: 127-42.2 Hamilton JR, Freeman H, eds. Dangerousness psychiatric assessment and
management London. Gaskell, for the Royal College of Psychiatrists (availablefrom Headley Brothers Ltd, Queen’s Rd, Ashford, Kent TN24 8HH) 1982 Pp.121. £4 75.
in assessing dangerousness than members of many otherdisciplines". T. Harding and C. Montandon, in a cross-cultural comparison, found a 57% level of agreement inassessing dangerousness for the case-histories of patientsfrom six countries-a level of prediction that is much betterthan chance but far too low to be of value in an individualcase.
The decision whether and when to discharge a patient whohas acted dangerously in the past is an exercise in the analysisof risk that would frighten the most accomplished actuary.Most authorities agree that, to ensure that patients who are adanger to society do not leave hospital prematurely, at leasttwo or three times as many patients will be detained
unnecessarily. Those who are wrongly detained are deprivedof their rights in a way that is unacceptable to the civillibertarians. In the United States several such patients havebeen judged unconstitutionally detained, and this has led tothe release of many mentally ill people against the advice oftheir clinicians; and follow-up of these patients has shown amuch lower incidence of violence than was predicted.3-5Unfortunately there is no way of predicting when re-offencesare likely to arise and a long period of follow-up is necessarybecause repetition of arson, rape, and homicide may takeplace many years after release.6,7 Most re-offences occurwithout any warning and are impossible to prevent by meansother than detention.The ethical aspects of dangerousness are discussed by
N. Walker in a thoughtful contribution to the symposiumthat develops a theme of an earlier paper. He emphasises thatthe decision whether or not to release a mentally abnormaloffender is one that appeals to values rather than relies onobjective evidence or statistical risk. If detention in hospitalmay prevent lasting hardship to others; if the original offencewas consistent with the patient’s personality and behaviour inhospital; if the circumstances of the original offence still exist;and if no other form of protection other than detention ispossible-then it is acceptable to keep the offender in
hospital, but only under conditions that are civilised andtolerable. The hazard of relying on value judgments is shownby the later contributions from A. Bothams and D. West, whodisagree with the "protectionist" policy and argue for a moregenerous attitude towards offenders.We are left with an unenviable position because, in
Tennent’s words,9 "in predicting rare behaviour there will bemore false positives than accurate predictions". Those whoare unfortunate enough to be caught amongst the false
positives have cause for complaint. Those responsible for thedetention and treatment of the apparently dangerous patientneed to stress their case, lest the rate of false negatives increaseand determine the reaction of society.
HORMONES AND FLUID RETENTION IN CIRRHOSIS
FLUID retention leading to ascites and peripheral oedema isa common feature of cirrhosis and advancing liver failure. Atfirst it usually responds to salt and water restriction,diuretics, and removal of the cause (for example, by alcohol
3 Steadman HJ, Keveles G. The community adjustment and criminal activity of theBaxtrom patients 1966-70. Am J Psychiatry 1972: 129: 304-10
4 Cocozza JJ, Steadman HJ Some refinements in the measurement and prediction ofdangerous behaviour. Am J Psychiatry 1974; 131: 1012-14
5. Thornberry TP, Jacoby JE. The criminally insane in a community follow-up ofmentally ill offenders. Chicago. Chicago University Press. 1979
6. Soothill KL, Pope PJ Arson: a 20 year cohort study Med Sci Law 1973, 13: 127-387. Soothill KL, Jack A, Gibbens TCN. Rape: a 22-year cohort study Med Sci Law 1976;
16: 62-69
8. Walker N. Dangerous people. Int J Law Psychiatry 1978. 1: 37-49.9. Tennent TG The dangerous offender. Br J Hosp Med 1971; 5: 269-74.
1342
withdrawal or by corticosteroid treatment of autoimmuneactive chronic hepatitis). Later, ascites may become
intractable, and heroic treatments such as the LeVeen
peritoneovenous shunt, or ascitic dialysis and reinfusion ofthe concentrated ascitic protein with the Rhone-Poulencpump,2 may be contemplated. Numerous hormones havebeen implicated in the pathogenesis of the fluid retention ofcirrhosis but there is no good objective evidence for a
deficiency of natriuretic hormone or a surplus of vasoactiveintestinal polypeptide.3 The roles of hyperaldosteronism inthe sodium retention 3,4 and vasopressin in the water
retention are still controversial.That sodium retention happens in cirrhosis is not in
question: many untreated patients are unable to excrete morethan 5 mmol sodium a day compared with the normal rate ofmore than 100 mmol. The old explanation was that
development of ascites leads to a reduction in the "effective"extracellular fluid and that the renin/angiotensin/aldosteronesystem is activated to restore the deficit. Reduced breakdownof aldosterone by the liver was also thought to play part. 6Evidence for hyperaldosteronism included the therapeuticefficacy of the aldosterone antagonist spironolactone in
reversing the sodium retention, the efficacy of
adrenalectomy, and the arterial hypotension induced insome patients by infusion of the angiotensin-11 antagonist,1-sarcosine 8-alanine angiotensin 11.8 If aldosterone weredominant in the aetiology of the sodium retention, one wouldexpect high renin activity and high concentrations ofaldosterone in plasma. In practice, three studies of cirrhoticswith ascites and sodium retention but not renal failure, showthat only about one-third of such patients have raised plasmarenin activity and plasma aldosterone levels, and plasmarenin activity and angiotensin are positively correlated withaldosterone levels.4,9,10 The increased plasma renin activityseems to be related to hyponatraemia and the shunting ofrenal blood flow from outer cortical to juxtamedullarynephrons. The lack of activation of the renin/angiotensin/aldosterone system in two-thirds of the patients casts doubton a dominant role of aldosterone in sodium retention; but,since sodium retention is related to plasma and urinaryaldosterone levels, there is still the possibility thataldosterone receptors are hypersensitive in cirrhotic
patients.4 .
The investigation of arginine vasopressin (mammalianantidiuretic hormone) in the pathogenesis of disease has beenhampered by the unreliability of plasma radioimmunoassays:
1. Epstein M. Peritoneovenous shunt in the management of ascites and the hepatorenalsyndrome. Gastroenterology 1982; 82: 790-99.
2. Lévy VG, Opolon P, Pauleau N, Caroli J. Treatment of ascites by reinfusion ofconcentrated peritoneal fluid-review of 318 procedures in 210 patients. PostgradMed J 1975; 51: 564-66.
3. Epstein M. Deranged sodium homeostatis in cirrhosis Gastroenterology 1979; 76:622-35
4. Wilkinson SP, Williams R. Renin-angiotensin-aldosterone system in cirrhosis. Gut1980; 21: 545-54.
5. Bichet D, Szatalowicz V, Chaimovitz C, Schrier RW. Role of vasopressin in abnormalwater excretion in cirrhotic patients. Ann Intern Med 1982, 96: 413-17
6. Vecsei P, Düsterdieck G, Jahnecke J, Lommer D, Wolff HP. Secretion and turnover ofaldosterone in various pathological states. Clin Sci 1969; 36: 241-56.
7. Henley KS, Streeten DHP, Pollard HM. Hyperaldosteronism in liver disease. Thetreatment of refractory ascites by adrenalectomy and by the administration ofspironolactones. Gastroenterology 1960, 38: 681-89.
8. Schroeder ET, Anderson GH, Goldman SH, Streeten DHP. Effect of blockade ofangiotensin II on blood pressure, renin and aldosterone in cirrhosis. Kidney Int1976; 9: 511-19.
9. Epstein M, Levinson R, Sancho J, Haber E, Re R. Characterisation of the renin-aldosterone system in decompensated cirrhosis. Circ Res 1977; 41: 818-29
10. Wernze H, Spech HJ, Müller G Studies on the activity of the renin-angiotensm-aldosterone system (RAAS) in patients with cirrhosis of the liver. Klin Wschr 1978;56: 389-97.
three early studies with bioassay techniques yieldedconflicting results. Work in laboratory animals suggests thatvasopressin may be a factor in the water retention of liverdisease. When the bileduct was ligated in Brattleboro rats (aspecial strain with hypothalamic diabetes insipidus) and incontrol rats, the Brattleboro rats handled a water load
normally whereas the control rats showed water retention."Similarly, normal rats with carbon-tetrachloride-inducedcirrhosis could not excrete a water load and their plasmaarginine vasopressin concentrations were raised, whereasBrattleboro rats with comparable liver disease handled awater load normally.12 In the dog, acute portal veinconstriction reduces the ability to excrete water and thisabnormality is partly corrected when endogenousvasopressin secretion is stopped by hypophysectomy. 13The inability of cirrhotic patients to handle a water load 14 is
clinically important. Hyponatraemia is common, causes
thirst, and thus encourages water ingestion. Indirect evidencefor a role of vasopressin in water retention comes from theobservation that alcohol I and demeclocycline,16 bothinhibitors of vasopressin secretion, increase urine flow anddecrease urine osmolarity. Bichet et al. tried the effect of a 20ml/kg water load on 12 stable alcoholic cirrhotic patients andfound in 7 patients a reduced water excretion (mean 27 - 3% in5 h) associated with a failure to dilute urine to below 262mosmol/kg; this inability to excrete a water load wasassociated with inappropriately high plasma argininevasopressin levels, whereas the 5 patients who handled theload normally had unmeasurably low concentrations. The 7patients unable to excrete the load had more severe liverdisease and more ascites than the 5 who responded morenormally. Bichet and co-workers concluded that vasopressinsecretion is stimulated non-osmotically by a decrease in"effective" blood volume and that this is a factor in theabnormal water secretion seen in cirrhotic patients. Blendis etal. 17 likewise found raised plasma vasopressin levels incirrhotic patients with severe ascites but after insertion of aLeVeen peritoneovenous shunt urine output, plasmasodium, and osmolar clearance increased, and urine
osmolarity decreased, but plasma vasopressin was
unchanged. These data suggest that in this situation theimprovement in water clearance is unrelated to vasopressinand probably results from intravascular volume expansionand increased delivery of glomerular filtrate to the distalnephron segment. As with the renin/angiotensin/aldosteronesystem and sodium retention, there seems to be more to waterretention in cirrhotics than vasopressin, and intrarenalfactors which are probably not hormonally mediated-suchas the reduced renal blood flow due to renal arteryvasoconstriction and corticomedullary shunting ofblood-must be implicated.
11. Better OS, Aisenbrey GA, Berl T, et al Role of antidiuretic hormone in impairedurinary dilution associated with chronic bile-duct ligation. Clin Sci 1980, 58:493-500.
12. Linas SL, Anderson RJ, Guggenheim SJ, Robertson GL, Berl T. Role of vasopressin inimpaired water excretion in conscious rats with experimental cirrhosis Kidney Int1981; 20: 173-80.
13 Anderson RJ, Cronin RE, McDonald KM, Schrier RW. Mechanisms of portalhypertension induced alterations in renal hemodynamics, renal water excretion andrenin excretion. J Clin Invest 1976; 58: 964-70
14. Klinger EL Jr, Vaamonde CA, Vaamonde LS, et al. Renal function changes in cirrhosisof the liver Arch Intern Med 1970; 125: 1010-15
15. Strauss MP, Birchard WH, Saxon L. Correction of impaired water excretion incirrhosis ofthe liver by alcohol ingestion or expansion of extracellular fluid volumethe role of antidiuretic hormone Trans Assoc Am Phys 1956; 69: 222-28.
16. De Troyer A, Pillay W, Bioechaert I, Demanet JC Demeclocycline treatment of waterretention in cirrhosis. Ann Intern Med 1976, 85: 336-37
17. Blendis LM, Reznick RK, Langer B, Taylor BR, Seif S. Hyponatraemia and ADHsecretion in hepatic ascites. Gut 1982, 23: A449
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