Interpretation of simultaneous measurements of hepatic extraction fractions of indocyanine green and sorbitol: evidence of hepatic shunts and capillarization?

Sorbitol and indocyanine green (ICG) have high hepatic extraction fractions (E(sorb) and E(ICG)) in normal subjects. A curved relationship has been observed between E(sorb) and E(ICG) in liver disease. According to one interpretation, the decrease of E(sorb) is a result of intrahepatic shunting and 1 - E(sorb) is the fraction of shunted flow (the shunt hypothesis). Under the further assumption that capillarization of functioning sinusoids prevents hepatic uptake of plasma protein-bound ICG and allows uptake of water-soluble sorbitol, the difference E(sorb) - E(ICG) has been suggested as a measure of capillarization. We propose an alternative hypothesis: that the sinusoidal permeability-surface area products for sorbitol and ICG are reduced in proportion by liver disease (proportional reduction hypothesis). Based on the sinusoidal perfusion model, predictions were produced from both hypotheses for the relation between E(sorb) and E(ICG) and the additional effects of capillarization were described. By use of liver vein catheterization, E(sorb) and E(ICG) were simultaneously measured during continuous infusions in 53 human subjects with varying degrees of liver disease. The data were in better agreement with the predictions of the proportional reduction hypothesis than with the shunt hypothesis. Even though both intrahepatic portosystemic shunts and sinusoidal capillarization are known to occur in cirrhosis and also may have influenced our data, they appeared to be of minor importance from a kinetic point of view. These findings favor the proportional reduction hypothesis and do not support the use of systemic nonrenal clearance of sorbitol as a measure of "functional liver blood flow."

Plasma cholecystokinin and its precursors in hepatic cirrhosis.

BACKGROUND/AIMS: The liver influences the metabolism of several peptide hormones. The metabolic effect may, however, change considerably by diseases in the liver. This study examined whether hepatic cirrhosis influences the occurrence and concentrations of procholecystokinin (proCCK) and its products in plasma. METHODS: The sum of proCCK and its products (both processing intermediates and bioactive fragments) in plasma were measured by a recently developed "processing-independent analysis". Bioactive forms of CCK in plasma were measured using a highly specific radioimmunoassay directed against the C-terminal epitope of CCK. RESULTS: In plasma from patients with primary biliary cirrhosis the basal concentration of the total proCCK product was increased. Moreover, a mixed meal increased plasma concentrations of both bioactive CCK (i.e. carboxyamidated an 0-sulfated CCK peptides) and the total proCCK product in primary biliary cirrhosis. In contrast, plasma concentrations of bioactive CCK and the total proCCK product were normal in patients with alcoholic liver cirrhosis-both pre- or postprandially. The fraction of bioactive CCK in plasma from patients with both biliary and alcoholic cirrhosis was also normal. Hence, in primary biliary cirrhosis, alcoholic cirrhosis and in controls, respectively, bioactive CCK constituted 15%, 15% and 17% of the total proCCK product in the basal state; 70%, 58% and 53% 30 min after and 48%, 56% and 51% 90 min after the meal. As shown by gel chromatography, plasma from patients with primary biliary cirrhosis and controls sampled 30 min after a meal contained CCK-33, -22 and -8-like peptides. In addition, plasma contained non-amidated (approximately non-bioactive) proCCK products corresponding in size to CCK-83, -58 and -33. Ninety minutes after a meal, CCK-8 predominated in plasma from patients with primary biliary cirrhosis, whereas plasma from controls displayed a CCK profile similar to that obtained 30 min post-prandially. CONCLUSIONS: The results show that CCK-8 is metabolized at a slower rate in patients with primary biliary cirrhosis.

Urological septicemia. A retrospective study.

In order to investigate the clinical course and outcome of septicemia in urological patients, data were collected retrospectively from all patients admitted to a specialized urological department, in whom positive blood cultures were drawn. During a 5-year period 91 patients were registered with urosepsis corresponding to an incidence of 1.2%. In non-iatrogenic urosepsis due to ureteral obstruction women dominated over men, however, in iatrogenic disease--after investigative manoeuvres as well as after surgery--men by large dominated the material. Gram-negative bacteria were responsible for almost 75% of the septicemias and for 99% of the cases where septic shock was present. Where a urinary infection was demonstrated prior to septicemia (45%- identical bacteria were subsequently found in the blood, whether the focus had been successfully treated or not. Septic shock developed in 20 of the patients of whom 3 died. This overall mortality of 3% occurred only in patients with comcomitant serious disease. In general the course of septicemia was benign and the complication rate low. It is concluded that in urological patients septicemia is a less serious problem than in gastroenterological patients. The possible explanation for this is discussed in relation to the more discrete diagnostic and therapeutical procedures in the urological clinic.