Hyperdynamic circulation of advanced cirrhosis: a re-appraisal based on posture-induced changes in hemodynamics.

Little is known about the effect of posture on the circulatory abnormalities of advanced cirrhosis. We evaluated the systemic hemodynamics, measured by Doppler-echocardiography, atrial natriuretic factor, plasma renin activity and plasma norepinephrine, in 10 patients with cirrhosis and ascites and 10 healthy controls, after 2 h of standing and during lying down for a further 2 h. Standing hemodynamic patterns of controls and patients with cirrhosis did not differ significantly. The latter, however, showed higher plasma renin activity, norepinephrine and atrial natriuretic factor. The assumption of the supine position led to greater increases in cardiac index and atrial natriuretic factor, and reduction in systemic vascular resistance in patients with cirrhosis. Norepinephrine and plasma renin activity declined in both groups to a similar extent, while heart rate only slowed in controls. Thus, after 2 h in the supine position, patients with cirrhosis showed hyperdynamic circulation with increased cardiac index and heart rate and reduced systemic vascular resistance. Norepinephrine, plasma renin activity and atrial natriuretic factor were also elevated. The hyperdynamic circulation in advanced cirrhosis appears during or is enhanced by lying down. This finding suggests that this syndrome is, at least in part, attributable to excessive blood volume translocation towards the central area. However, the persistent activation of renin-angiotensin and sympathoadrenergic systems suggests that a concomitant reduced vascular sensitivity to vasoconstrictors concurs in its development.

Renal sodium handling in cirrhosis with ascites: mechanisms of impaired natriuretic response to reclining.

We recently showed that patients with compensated cirrhosis can dispose of their fluid overload while reclining. In contrast, patients with ascites fail to develop supine-induced natriuresis. To assess the effect of reclining on renal sodium handling in patients with advanced cirrhosis and the mechanisms blunting natriuresis in this situation, renal function and plasma concentrations of atrial natriuretic factor, aldosterone and norepinephrine were evaluated in 10 nonazotemic patients with cirrhosis and ascites and 10 healthy controls standing for 2 h and reclining for 2 h. While standing, all patients showed marked sodium retention and significantly elevated plasma atrial natriuretic factor levels, aldosterone and norepinephrine. Glomerular filtration rate did not differ from healthy controls. The reclining increased renal sodium excretion in both groups, but this change was far less marked in patients; natriuresis only rose to the control range in two of them. An increase in atrial natriuretic factor and a depression of plasma aldosterone and norepinephrine was seen in both controls and patients. In the latter, despite the greater change in atrial natriuretic factor and aldosterone, the aldosterone to atrial natriuretic factor ratio, which was inversely correlated with natriuresis during both standing and reclining remained significantly elevated. In the two patients who achieved normal natriuresis during reclining, reclining was associated with both the normalization of the aldosterone/atrial natriuretic factor ratio, and with an increase in glomerular filtration rate. The supine-induced increase in atrial natriuretic factor was not only preserved but was even enhanced in cirrhosis with ascites.(ABSTRACT TRUNCATED AT 250 WORDS)

Gross pathologic types of hepatocellular carcinoma in Italian patients. Relationship with demographic, environmental, and clinical factors.

BACKGROUND: The prevalence of the different hepatocellular carcinoma (HCC) macroscopic types, and the association between these types and age, gender, blood group, alcohol and coffee intake, smoking habit, hepatitis virus markers, underlying cirrhosis, and cancer histologic type were retrospectively assessed in 416 unselected patients (321 with cirrhosis). METHODS: The gross pathologic types of HCC were assessed by ultrasonography combined, in most cases, with computed tomography and angiography. RESULTS: Solitary HCC was the most common cancer type (54.8%), followed by the multinodular (31%), diffuse (7.7%), and massive (6.5%) types. Cirrhosis and blood group other than O were independent risk factors for multinodular HCC (relative risk [RR] 1.6, P < 0.05; and RR 1.7, P < 0.005, respectively); the absence of cirrhosis and a heavy smoking habit were risk factors for the massive type (RR 4.9, P < 0.001; and RR 3.3, P < 0.01, respectively); and blood group O for the solitary type (RR 1.4, P < 0.001). The prevalence of highly undifferentiated cells increased as the tumor size did, so that grade IV cell atypia was associated with massive size of the carcinoma (P < 0.05). In cirrhotic patients, advanced liver dysfunction was associated with diffuse HCC (P < 0.05). As far as solitary HCC is concerned, the tumor size was greater in noncirrhotic than in cirrhotic patients (7 +/- 0.4 cm versus 4.8 +/- 0.15, P < 0.001). CONCLUSIONS: In Italian patients, HCC presents most frequently as a solitary nodule. The presence or absence of cirrhosis, blood group, and smoking habit can influence the likelihood of developing certain HCC shapes. The probability of harboring highly undifferentiated cells increases as the cancer increases in size. In cirrhosis, advanced liver dysfunction may predispose to diffuse HCC.

Renal sodium retention during upright posture in preascitic cirrhosis.

BACKGROUND: Renal sodium handling in preascitic cirrhosis is not clearly defined. This issue was addressed by evaluating renal sodium metabolism with different postures. METHODS: Renal function and plasma atrial natriuretic factor (ANF), aldosterone, and norepinephrine levels were determined after 2 hours of standing and 30, 60, and 120 minutes after taking up the supine position in 10 patients and 10 healthy subjects. RESULTS: When upright, patients' glomerular filtration rate and plasma ANF and norepinephrine levels did not differ from those of controls. Conversely, renal sodium excretion was reduced. Plasma aldosterone levels, which were slightly elevated, inversely correlated with renal sodium excretion. In the supine position, natriuresis increased by 308% +/- 99% in patients and 113% +/- 29% in controls (P = 0.016), so that it no longer differed between the two groups. Plasma norepinephrine and aldosterone levels decreased to a similar extent in controls and cirrhotics, whereas the increase in plasma ANF level was greater in patients. The changes in natriuresis correlated with those in plasma ANF levels and plasma aldosterone-ANF ratios in both controls and patients. CONCLUSIONS: Aldosterone-dependent sodium retention develops in preascitic cirrhosis during standing. The supine position is the means whereby standing-induced sodium retention can be balanced.

The hemodynamic status of preascitic cirrhosis: an evaluation under steady-state conditions and after postural change.

To assess the hemodynamic status of patients with compensated cirrhosis, mean arterial pressure, cardiac index and peripheral vascular resistance and markers of central (plasma concentrations of atrial natriuretic factor) and arterial volemia (plasma norepinephrine concentration, plasma renin activity) were studied in 10 patients and 10 healthy control subjects under steady-state conditions (after 2 hr of standing) and after assumption of the supine position (30, 60, and 120 min). After standing, neither hemodynamics nor markers of effective volemia differed significantly between controls and patients. By evaluating the areas under the curve during the 2 hr of supine posture, the increase in cardiac output and plasma natriuretic factor and the decrease in peripheral vascular resistance were greater in patients (2.59 +/- 0.43 [S.E.M.] L/min/hr; 32.8 +/- 7.2 pg/ml/hr -1,103 +/- 248.4 dyn.sec/cm5/hr, respectively) than in controls (0.53 +/- 0.24 L/min/hr, p = 0.005; 17.4 +/- 4.7 pg/ml/hr, p = 0.005; -265.5 +/- 206.2 dyn.sec/cm5/hr, p = 0.02). The declines in heart rate, plasma norepinephrine concentration and plasma renin activity did not differ significantly. Mean arterial pressure did not significantly change. Our results suggest that during periods of upright posture, cirrhotic patients in the preascitic stage, who are known to have expanded blood volume, compensate for dilatation of the splanchnic vascular bed through total hypervolemia. The latter becomes excessive during recumbency, leading to supernormal increases in venous return, central volemia and cardiac index. The decline in peripheral vascular resistance appears to be a compensatory mechanism to maintain steady arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)