Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus: auto-downregulation of pulmonary arterial blood supply.

It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V/Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days.

Cardiovascular complications of cirrhosis.

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis without adequate plasma volume expansion, transjugular intrahepatic portosystemic shunt (TIPS) insertion, peritoneovenous shunting and surgery. Cardiac failure is an important cause of mortality after liver transplantation, but improved liver function has also been shown to reverse the cardiac abnormalities. No specific treatment can be recommended, and cardiac failure should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and oxygen therapy when necessary. Special care should be taken with the use of ACE inhibitors and angiotensin antagonists in these patients. The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.

Cardiovascular complications of cirrhosis.

Cardiovascular complications of cirrhosis include cardiac dysfunction and abnormalities in the central, splanchnic and peripheral circulation, and haemodynamic changes caused by humoral and nervous dysregulation. Cirrhotic cardiomyopathy implies systolic and diastolic dysfunction and electrophysiological abnormalities, an entity that is different from alcoholic heart muscle disease. Being clinically latent, cirrhotic cardiomyopathy can be unmasked by physical or pharmacological strain. Consequently, caution should be exercised in the case of stressful procedures, such as large volume paracentesis without adequate plasma volume expansion, transjugular intrahepatic portosystemic shunt (TIPS) insertion, peritoneovenous shunting and surgery. Cardiac failure is an important cause of mortality after liver transplantation, but improved liver function has also been shown to reverse the cardiac abnormalities. No specific treatment can be recommended, and cardiac failure should be treated as in non-cirrhotic patients with sodium restriction, diuretics, and oxygen therapy when necessary. Special care should be taken with the use of ACE inhibitors and angiotensin antagonists in these patients. The clinical significance of cardiovascular complications and cirrhotic cardiomyopathy is an important topic for future research, and the initiation of new randomised studies of potential treatments for these complications is needed.

Validation of a self-administered modified CAGE test (CAGE-C) in a somatic hospital ward: comparison with biochemical markers.

OBJECTIVE: The time frame for the original CAGE questionnaire is lifetime and it does not quantify drinking frequency and may be less suitable in a population with very few teetotalers. The purpose of this study was to validate a variant of the CAGE questionnaire and compare it with the outcome of a thorough interview according to DSM-III and ICD-10 criteria and to the outcome of biochemical markers in inpatients in a somatic hospital setting. MATERIAL AND METHODS: The questionnaire and biochemical markers were tested on a random sample of 130 patients admitted to a department of orthopedic surgery. The result of a diagnostic interview with a trained staff member from the local alcohol treatment unit was used as the gold standard. Data were analyzed by means of receiver operating characteristic (ROC) curves. RESULTS: In this population 25 % had an alcohol problem and the questionnaire proved to be valid, with a sensitivity and specificity of 0.94 and 0.88, respectively, while the positive predictive value (PVpos) was 0.73 and the negative predictive value (PVneg) was 0.98. Carbohydrate-deficient transferrin (CDT) had a sensitivity and a specificity of 0.47 and 0.96, and PVpos and PVneg of 0.80 and 0.85, respectively. CONCLUSIONS: This new diagnostic questionnaire is simple, easy to administer and suitable for screening purposes in populations with a high prevalence of at-risk drinkers.

Review article: pathogenesis and pathophysiology of hepatorenal syndrome--is there scope for prevention?

The hepatorenal syndrome (HRS) is a functional impairment of the kidneys in chronic liver disease caused by a circulatory failure. The prognosis is poor, particularly with type 1 HRS, but also type 2, and only liver transplantation is of lasting benefit. However, recent research into the pathophysiology of ascites and HRS has stimulated new enthusiasm in their prevention and treatment. Patients with HRS have hyperdynamic circulatory dysfunction with reduced arterial blood pressure and reduced central blood volume, owing to preferential splanchnic arterial vasodilatation. Activation of potent vasoconstricting systems, including the sympathetic nervous and renin-angiotensin-aldosterone systems, counteracts the arterial vasodilatation and leads to a pronounced renal vasoconstriction with renal hypoperfusion, a reduced glomerular filtration rate, and intense sodium-water retention. Thus prevention of HRS should seek to improve liver function, limit arterial hypotension and central hypovolaemia, and reduce renal vasoconstriction and the renal and interstitial pressures. Portal pressure can be reduced with beta-adrenergic blockers and transjugular intrahepatic portosystemic shunt (TIPS). Precipitating events, like infections, bleeding, and postparacentesis circulatory syndrome, should be treated to avoid further circulatory failure. Improvement in arterial blood pressure and central hypovolaemia can be achieved with vasoconstrictors, such as terlipressin (Glypressin), and plasma expanders such as human albumin. In the future endothelins, adenosine antagonists, long-acting vasoconstrictors, and antileukotriene drugs may play a role in preventing and treating HRS.

Serum YKL-40 is increased in patients with hepatic fibrosis.

BACKGROUND/AIMS: YKL-40, a mammalian member of the chitinase family, is a lectin that binds heparin and chitin. The function of YKL-40 is unknown, but it may function in tissue remodelling. The aims of this study were to assess the level of circulating YKL-40 in patients with various kinds and degree of chronic liver disease and its possible relation to liver fibrosis. METHODS: Serum YKL-40 levels were determined by radioimmunoassay in 129 patients with suspected liver disease and related to histological findings and immunohistochemical staining of YKL-40 in a liver biopsy taken simultaneously with the blood sample. RESULTS: The median serum YKL-40 was highest in patients with alcoholic cirrhosis (532 microg/l), in particular in patients with additional alcoholic hepatitis (740 microg/l). Patients with alcoholic cirrhosis, post-hepatitic cirrhosis (425 microg/l) and non-cirrhotic fibrosis (330 microg/l) had significantly higher serum YKL-40 than normal subjects (102 microg/l), patients with fatty liver (195 microg/l) or patients with viral hepatitis without fibrosis (174 microg/l). Serum YKL-40 was significantly (p<0.001) related to the degree of liver fibrosis with the highest levels in patients with moderate (466 microg/l) to severe (676 microg/l) fibrosis. Serum YKL-40 was also increased (p=0.018) in patients with slight fibrosis (270 microg/l) compared to patients without fibrosis. Immunohistochemical analysis demonstrated positive staining for YKL-40 antigen in areas with fibrosis, particularly areas with active fibrogenesis. YKL-40 staining was never found in hepatocytes. CONCLUSIONS: Our study indicates that the increased serum YKL-40 in patients with liver disease of various degree and aetiology seems to reflect fibrosis and fibrogenesis.

Increased arterial compliance in decompensated cirrhosis.

BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension in patients with biopsy-verified cirrhosis (Child-Turcotte classes A/B/C=10/15/6). RESULTS: COMPart was significantly higher in cirrhotic patients (n=31) than in controls (n=10) (1.44 vs 1.00 x 10(-3) l/mmHg, p<0.01). It increased significantly through the Child-Turcotte classes A, B, and C (1.02, 1.47, and 2.1 x 10(-3) l/mmHg, respectively, p=0.03). The stroke volume did not change significantly with the severity of the disease, but pulse pressure decreased through class A, B, and C (79, 65, and 50 mmHg, respectively, p<0.01). COMPart was slightly, but significantly correlated to the circulating level of CGRP (r=0.34, p<0.05), and a substantial but inverse correlation was present to MAP (r= -0.63, p<0.002). CONCLUSIONS: Elevated arterial compliance in cirrhosis is directly related to the severity of the disease and to the elevated level of circulating vasodilator peptide CGRP, and inversely related to the level of arterial blood pressure. The altered static and dynamic functions of the arterial wall in cirrhosis may have implications for the circulatory and homoeostatic derangement, and potentially for therapy with vasoactive drugs.

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism.

BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

Neurohumoral fluid regulation in chronic liver disease.

Impaired homeostasis of the blood volume, with increased fluid and sodium retention, is a prevailing element in the deranged systemic and splanchnic haemodynamics in patients with liver disease. In this review, some basic elements of the circulatory changes that take place and of neurohumoral fluid regulation are outlined in order to provide an update of recent investigations on the neuroendocrine compensation of circulatory and volume dysfunction in chronic liver disease. The underlying pathophysiology is a systemic vasodilatation in which newly described potent vasoactive substances such as nitric oxide and vasodilating peptides seem to play an important role. The development of central hypovolaemia and activation of potent vasoconstricting systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system lead to a hyperdynamic circulation with increased heart rate and cardiac output. Moreover, patients exhibit an autonomic dys- and hyperfunction with vascular hyporeactivity to pressor stimuli. The circulatory dysfunction may be part of a multiorgan failure with disturbed haemodynamics of various vascular beds, including those of the splanchnic system, kidneys, brain and lungs. It is still an enigma why patients with chronic liver disease are at the same time overloaded and functional hypovolaemic with a hyperdynamic, hyporeactive circulation. Further research is needed to find the solution to this apparent haemodynamic conflict concerning the abnormal neurohumoral fluid regulation in chronic liver disease.

[Decompensation]. / Inkompensation.

Fluid and sodium retention with peripheral oedema and ascites are often seen in decompensated patients with diseases of the liver, kidney and heart and in malignancies. Despite a careful clinical examination including relevant biochemical tests, decompensation is associated with diagnostic challenges. Two cases are presented where a haemodynamic investigation of the splanchnic and systemic circulation contributed to the establishment of a correct diagnosis, and the advantages of this diagnostic tool are discussed.

Plasma YKL-40: a new potential marker of fibrosis in patients with alcoholic cirrhosis?

BACKGROUND: YKL-40 (human cartilage glycoprotein-39, or 38-kDa heparin-binding glycoprotein) is a mammalian member of a protein family that includes bacterial chitinases. YKL-40 mRNA is expressed by human liver and may play a role in tissue remodelling. The aims were to assess whether circulating YKL-40 is released or extracted in the hepatosplanchnic system and to localize YKL-40 in liver tissue. METHODS: Plasma YKL-40 was determined by radioimmunoassay in 25 patients with liver diseases (alcoholic cirrhosis (n = 20), chronic active hepatitis (n = 2), cirrhosis of unknown aetiology (n = 2), and fatty liver (n = 1) and in 18 subjects with normal liver function during a haemodynamic investigation with catheterization of liver vein and the femoral artery. Immunohistochemical studies of the localization of YKL-40 in cryostal liver biopsy specimens were obtained from eight other patients with alcoholic liver disease. RESULTS: Plasma YKL-40 was significantly increased in patients with alcoholic cirrhosis (median, 523 micrograms/l; P < 0.001) compared with controls (106 micrograms/l), and plasma YKL-40 in the hepatic vein was higher (P < 0.01) than that of the artery in both the patients and controls, showing release of YKL-40 from the hepatosplanchnic area. The release rate of YKL-40 from the hepatosplanchnic area was higher in patients with liver disease than in controls (11.0 versus 2.1 micrograms/min, P < 0.05). Furthermore, the highest plasma YKL-40 levels were found in patients with a moderate or severe degree of liver fibrosis, and immunohistochemical studies showed positive staining for YKL-40 antigen in areas of the liver biopsy with fibrosis. CONCLUSIONS: The increased plasma YKL-40 in patients with alcoholic cirrhosis may reflect the remodelling of liver fibrosis.

Endothelins in chronic liver disease.

This review describes recent progress in the accumulation of knowledge about the endothelins (ETs), a family of vasoactive 21-amino acid polypeptides, in chronic liver disease. Particular prominence is given to the dynamics of ET-1 and ET-3 and their possible relation to the disturbed circulation and neurohumoral dysregulation found in cirrhosis. Recent studies have shown that the ET system is highly activated in most cirrhotic patients. Circulating ET-1 and ET-3 levels have a positive relation to the severity of the disease and fluid retention, with the highest values recorded in patients with functional renal failure. Studies on liver biopsies have revealed synthesis of ET-1 in hepatic endothelial and other cells, and recent investigations have identified the hepatosplanchnic system as a major source of ET-1 and ET-3 spillover into the circulation, with a direct relation to portal venous hypertension. In addition, marked associations with disturbance of systemic haemodynamics and with abnormal distribution of blood volume have been reported. Although the pathophysiological importance of the ET system in chronic liver disease is not completely understood, similarities to other vasopressive and antinatriuretic regulatory systems (i.e. the sympathetic nervous system, renin-angiotensin-aldosterone and vasopressin) are apparent, with respect to kinetics and haemodynamic dysregulation. Cirrhosis seems to be a pathophysiological condition with indications of the occurrence of ETs, not only as local modulators, but also as a system with potential importance for systemic regulation.

Effect of oxygen inhalation on systemic, central, and splanchnic haemodynamics in cirrhosis.

BACKGROUND/AIMS: Patients with cirrhosis exhibit a hyperdynamic circulation with increased cardiac output and low arterial blood pressure. The aim of the present study was to assess the effects of oxygen inhalation on systemic, central, and splanchnic haemodynamics and vasoactive systems in patients with cirrhosis (n = 19). RESULTS: Spirometry was normal, but the carbon monoxide diffusing capacity (transfer factor) was significantly decreased, 18.8 ml.min-1.mmHg-1 (-32% of that predicted, p < 0.0001), and correlated significantly with the cardiac output (r = 0.78, p < 0.0005), plasma volume (r = 0.72, p < 0.001) and the central and arterial blood volume (r = 0.67, p < 0.005). After inhalation of 100% oxygen over a period of 20 min, the cardiac output decreased from 7.4 to 6.6 l/min (p < 0.0005), and the systemic vascular resistance increased from 980 to 1124 dyn.s.cm-5 (p < 0.005). The change in systemic vascular resistance was significantly greater in patients with mild liver dysfunction than in those with severe liver dysfunction (p < 0.02). In contrast, no significant changes were seen in the arterial or portal venous pressures during inhalation of oxygen. Arterial concentrations of catecholamines, renin, endothelin-1, and calcitonin gene-related peptide were all increased in patients with cirrhosis, but only the catecholamine concentrations decreased significantly (noradrenaline -13%, p < 0.02 and adrenaline -16%, p < 0.01) in response to oxygen. CONCLUSION: During oxygen inhalation cardiac output decreases and systemic vascular resistance increases in association with a decrease in arterial concentrations of catecholamine, but oxygen supply in patients with cirrhosis does not normalise the hyperdynamic circulation or the low arterial blood pressure.

[Portal hypertensive gastropathy]. / Portal hypertensiv gastropati.

Portal hypertensive gastropathy (PHG) as defined by congestive changes in the gastric mucosa owing to increased portal pressure, was first described about ten years ago. Whereas definition and grading of severity are still under debate, there is general agreement that PHG is a new clinical entity. PHG is present in 50-80% of patients with liver cirrhosis. PHG is a major cause of upper gastrointestinal bleeding in patients with portal hypertension (25-90% depending on severity). Presence of portal hypertension is a prerequisite for the development of PHG, and reduction of portal pressure and splanchnic blood flow with beta-adrenergic blockers has shown promising results, but an established medical treatment of PHG does not exist. Trials with new vasoactive drugs are awaited.

Carbohydrate-deficient transferrin--a valid marker of alcoholism in population studies? Results from the Copenhagen City Heart Study.

Carbohydrate-deficient transferrin (CDT) was analyzed by a modified radioimmunoassay test in a random population sample of 400 individuals, and results were compared with reported alcohol intake derived from a structured questionnaire. Among the 180 men, the test was found to be acceptable with respect to detecting harmful alcohol intake (> 35 beverages/week) and alcohol intake above the recommended level (21 beverages/week), although the positive predictive values were low. Among the 220 women, the test was invalid with low predictive values. CDT was compared with other known markers of high alcohol intake, and it was observed that CDT had higher sensitivity and specificity than AST and short Michigan Alcoholism Screening Test (sMAST) in men, whereas the positive and negative predictive values were low in all tests. A combination of CDT and AST proved to be a better marker of both harmful alcohol intake and alcohol intake above the recommended level than the other markers. Neither CDT, AST, CDT/AST, nor sMAST proved to be useful as markers of alcohol intake in women. There were no differences between the values for pre- and postmenopausal women. These results from a population survey indicate that CDT is a marker of alcohol intake among men, although not ideal, but CDT cannot be used in the screening of harmful alcohol intake in women.

Bisphosphonate kinetics in patients undergoing continuous ambulatory peritoneal dialysis: relations to dynamic bone histomorphometry, osteocalcin and parathyroid hormone.

In the evaluation of renal osteodystrophy bone biopsy is often performed. However, a reliable noninvasive test could be very useful, and recently the estimation of osseous tracer uptake as an index of bone formation has been introduced-the bone bisphosphonate clearance (BBC). The aim of the present investigation therefore was to compare BBC with parameters of bone histology, serum levels of osteocalcin, alkaline phosphatase, and parathyroid hormone in patients (n = 8) undergoing continuous ambulatory peritoneal dialysis (CAPD). No significant correlations were found between BBC values and the bone histomorphometrical variables measured. A positive correlation was seen between serum osteocalcin and resorption and active resorption surface (p < 0.05), as well as tetracycline-labelled surface, bone formation rate, surfaces, volume and tissue referents, respectively (p < 0.01). Furthermore, levels of alkaline phosphatase showed significant correlations to mineral appositional rate, tetracycline-labelled surface and bone formation rate, volume referent (p < 0.05). Values of parathyroid hormone were significantly correlated to resorption surface (p < 0.02), active resorption surface, mineral appositional rate and mineralization lag time (p < 0.05). In conclusion, BBC was of no use in patients treated with CAPD as a noninvasive test for evaluation of bone histomorphometry. However, osteocalcin correlated best with resorption and bone dynamics indices. Levels of alkaline phosphatase and parathyroid hormone were of a more limited value.

Long-term effects of oral propranolol on splanchnic and systemic haemodynamics in patients with cirrhosis and oesophageal varices.

Splanchnic and systemic haemodynamics were measured in 24 patients with cirrhosis and oesophageal varices and no previous bleeding. The patients were randomized either to long-term treatment with propranolol (14 patients) or no active treatment (controls, 10 patients). Catheterization was performed again 1 year after randomization. After 1 year of treatment the hepatic venous pressure gradient had decreased in both the propranolol and control group (-16% versus -24% (NS), respectively). Hepatic blood flow decreased substantially in both groups but significantly more in the propranolol group (-39% versus -17% (p less than 0.05), respectively). Azygos blood flow was significantly reduced after 1 year in the propranolol group (-47%, n = 5 (p less than 0.05)), and no obvious effect was observed in the control group (-2%, n = 4). The cardiac index decreased significantly in the propranolol group but not in the control group (-20% versus -1% (p less than 0.05), respectively). Our results demonstrate that the splanchnic hyperdynamic condition observed in cirrhosis is in some of the patients partly reversible without pharmacologic treatment. No additional effect of propranolol was observed on portal pressure after 1 year of treatment with propranolol, whereas a decrease in azygos blood flow was observed only in the propranolol group. The beneficial effect of propranolol on the risk of bleeding from oesophageal varices may, therefore, mostly be due to a selective decrease in collateral blood flow and thereby variceal blood flow.

The effect of 0.5% ropivacaine on epidural blood flow.

Twenty patients scheduled for elective abdominal surgery received epidural analgesia with 20 ml 0.5% ropivacaine or 0.5% bupivacaine. Epidural blood flow was measured by an epidural 133Xe clearance technique on the day before surgery (no local anaesthetic) and again 1 h before surgery, 30 min after injection of the local anaesthetic during continuous infusion (8 ml/h). Median initial blood flow was 5.0 ml/min and 6.0 ml/min per 100 g tissue in patients receiving ropivacaine and bupivacaine, respectively. After epidural bupivacaine, blood flow increased in 8 of 10 patients to 6.9 ml/min per 100 g tissue (P less than 0.05) in contrast to a decrease in 9 of 10 patients to 3.3 ml/min per 100 g tissue after ropivacaine (P less than 0.05), (P less than 0.01 between groups). The median level of sensory analgesia was T3.5 and T4.5 in the ropivacaine and bupivacaine group, respectively (P greater than 0.05). The demonstrated vasoconstrictor effect of epidural ropivacaine may influence the duration of its local anaesthetic effect.