Arterial hypoxaemia in cirrhosis: fact or fiction?

Background—Although low arterial oxygen tension (PO(2)) has been claimed to occur in one to two thirds of patients with cirrhosis, hypoxaemia appears to be rare in clinical practice. 
Aims—To assess the frequency of arterial hypoxaemia in cirrhosis in relation to clinical and haemodynamic characteristics. 
Patients—One hundred and forty two patients with cirrhosis without significant hepatic encephalopathy (grades 0-I) (41 patients in Child class A, 57 in class B, and 44 in class C) and 21 patients with hepatic encephalopathy. 
Results—Mean PO(2) in kPa was 11.3 in Child class A, 10.8 in class B, 10.6 in class C, and 10.6 in patients with encephalopathy (p<0.05). The fraction of patients with PO(2) below the lower normal limit of 9.6 kPa was 10%, 28%, 25%, and 43%, respectively in class A, B, C, and in patients with encephalopathy (p<0.05). Oxygen saturation (SO(2)) in these groups was respectively: 96%, 96%, 96%, and 93% (NS). SO(2) was below the lower limit of 92% in 0%, 9%, 7%, and 24% (p<0.05). In patients without hepatic encephalopathy, a multivariate regression analysis revealed that independent determinants of a low PO(2) were a high arterial carbon dioxide tension, a low systemic vascular resistance, and a low indocyanine green clearance (p<0.0001). 
Conclusion—The prevalence of arterial hypoxaemia in cirrhosis is about 22% in patients without encephalopathy, but it varies from 10-40% depending on the degree of hepatic dysfunction. Arterial hypoxaemia in patients with cirrhosis of differing severity seems lower than previously reported, and patients with severe arterial hypoxaemia are rare. 

 Keywords: cirrhosis; encephalopathy; haemodynamics; hepatopulmonary syndrome; hyperdynamic circulation; hypoxaemi

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. 

 Keywords: bone mineral density; carboxy terminal cross linked telopeptide of type I collagen; chronic liver disease; fibrosis; hepatic osteodystrophy; portal hypertensio

Omeprazole promotes proximal duodenal mucosal bicarbonate secretion in humans.

The proton pump inhibitor, omeprazole, surprisingly resulted in higher rates of proximal duodenal mucosal bicarbonate secretion than previously reported using an H2 receptor antagonist for gastric acid inhibition. Gastroduodenal perfusions were performed in healthy volunteers to evaluate whether this incidental finding is explained by more potent gastric acid inhibition by omeprazole or might be caused by the different mode of drug action. Basal and stimulated gastric and duodenal bicarbonate secretion rates were measured in the same subjects in control experiments (n = 17) and after pretreatment with high dose omeprazole (n = 17) and ranitidine (n = 9), respectively, by use of a technique permitting simultaneous measurements. Concentrations of bicarbonate were measured in the respective effluents by the method of back titration. Both omeprazole and ranitidine completely inhibited gastric acid secretion (pH 6.9 v 6.8; p > 0.05). Omeprazole caused higher rates of basal (mean (SEM)) (597 (48) v 351 (39) mumol/h; p < 0.02) and vagally stimulated (834 (72) v 474 (66) mumol/h; p < 0.02), but not acid stimulated (3351 (678) v 2550 (456) mumol/h; p > 0.05) duodenal bicarbonate secretion compared with control experiments. Also the combination of omeprazole and ranitidine increased (p = 0.05) duodenal bicarbonate secretion, while ranitidine alone caused no change in either basal or stimulated secretion. In the stomach basal as well as vagally stimulated bicarbonate secretion was independent of the means of acid inhibition. These results show that the proton pump inhibitor, omeprazole, promotes proximal duodenal mucosal bicarbonate secretion apparently independent of its gastric acid inhibitory effect. The mechanism of action remains speculative

Characterization of the Cysteinyl Leukotriene 2 Receptor in Novel Expression Sites of the Gastrointestinal Tract

Cysteinyl leukotrienes (cysLTs: LTC4, LTD4, and LTE4) are pro-inflammatory lipid molecules synthesized from arachidonic acid. They exert their actions on at least two cysLT receptors (CysLT1R and CysLT2R). Endothelial expression and activation of these receptors is linked to vasoactive responses and to the promotion of vascular permeability. Here we track the expression pattern of CysLT2R in a loss-of-function murine model (CysLT2R-LacZ) to neurons of the myenteric and submucosal plexus in the small intestine, colonic myenteric plexus, dorsal root ganglia, and nodose ganglion. Cysteinyl leukotriene (LTC4/D4) stimulation of colonic submucosal venules elicited a greater permeability response in wild-type mice. In a dextran sulfate sodium-induced colon inflammation model, the disease activity index and colonic edema (measured by wet:dry weights and submucosal thickness) were significantly reduced in knockout (KO) mice compared to controls. Tumor necrosis factor-α levels in colon tissue were significantly lower in KO mice; however, myeloperoxidase activity was similar in both the KO and wild-type groups. Finally, patch-clamp recordings of basal neuronal activity of colonic-projecting nociceptive neurons from dorsal root ganglia (T9-13) revealed significantly higher excitability in KO neurons compared to wild type. These results suggest that a lack of neuronal expression of CysLT2R in the murine colonic myenteric plexus attenuates colitis disease progression via a reduction in inflammation-associated tissue edema and increases neuronal sensitivity to nociceptive stimuli