Portal hypertension. Update on pathophysiology and management.

A lot has been learned about the pathophysiology of portal hypertension and its complications. This knowledge has led to vast advancements in therapy for this serious disease. I believe the future will carry more breakthroughs in therapy intercepting earlier steps in the disease process such as arresting fibrogenesis, inducing fibrinolysis or possibly targeting vascular remodeling and neovessel formation or employing hepatocytes transplantation.

Local arterial vasoconstriction induced by octreotide in patients with cirrhosis.

Peripheral vasodilation initiates the hyperdynamic circulation in cirrhosis. Somatostatin and its analogues, such as octreotide, have a vasoconstrictive effect in cirrhotic patients and experimental animals with portal hypertension. The exact mechanism of octreotide-induced vasoconstriction remains unknown. To investigate whether octreotide produces vasoconstriction through suppression of vasodilatory peptides, such as glucagon, or through a local effect, we evaluated the effect of an intra-arterial dose on forearm blood flow (FBF), while measuring systemic glucagon levels. FBF was measured in 10 cirrhotic patients by venous occlusion plethysmography. The brachial artery of the nondominant arm was catheterized, and vasoactive drugs were administered: methacholine 4 microg/min; octreotide 20 microg/h, and octreotide 20 microg/h + methacholine 4 microg/min. Each infusion, lasting 5 minutes, was followed by saline for washout. FBF was measured in both arms during the last minute of each infusion and at the end of washout, with the uninfused arm acting as the control. Nitrates and nitrites, octreotide, and glucagon blood levels were determined at baseline and after each infusion. Percent change in flow (%triangle up) was obtained by comparing the flow during drug administration to that during the preceding saline infusion. Saline infusion did not alter FBF, but octreotide infusion resulted in a 34% +/- 7.7 (P <.005) reduction in FBF in the infused arm. FBF in the control arm was unchanged despite a significant decrease in systemic glucagon levels. Methacholine infusion increased FBF around 300%, which was not altered by the concomitant infusion of octreotide. Octreotide has a local vasoconstrictive effect that seems nitric oxide (NO)-independent. Octreotide probably has a facilitating effect over vasoconstrictors increased in chronic liver diseases.

Differential diagnosis of bile duct injury and ductopenia.

Injury and loss of intrahepatic bile ducts are relatively common manifestations of liver disease in both adults and children. They occur in a wide variety of conditions ranging from developmental abnormalities and errors of metabolism to autoimmune disorders, infections, and iatrogenic states. Consequently the differential diagnosis is often complex. Moreover, although duct injury is generally easily detected in needle biopsy specimens, ductopenia is not infrequently both overlooked and overdiagnosed. This article reviews the differential diagnosis of duct injury and ductopenia in liver biopsy specimens and provides an algorithmic framework for narrowing down the differential diagnosis before correlation with the clinical findings.

Intestinal pseudoobstruction in acute Lyme disease: a case report.

We report here a case of acute Lyme disease in a 61-yr-old man who developed a facial nerve paralysis and a relentless intestinal pseudoobstruction 2 wk after the initial prodrome. Both the facial nerve paralysis and pseudoobstruction persisted for a month until the patient sought medical attention. Both lesions resolved only after treatment for Lyme disease was initiated. The temporal association of the pseudoobstruction with the somatic cranial neuropathy and the response of both to specific therapy for Lyme disease suggest that the former was likely the result of a reversible autonomic neuropathy or dysfunction.

Hepatomegaly and abnormal liver tests due to glycogenosis in adults with diabetes.

In adults with diabetes mellitus, hepatomegaly and abnormalities of liver enzymes occur as a consequence of hepatocellular glycogen accumulation, as has been well described in children. During periods of hyperglycemia glucose freely enters the hepatocytes driving glycogen synthesis, which is augmented further by administration of insulin to supraphysiologic levels. The accumulation of excessive amounts of glycogen in the hepatocytes is a function of intermittent episodes of hyperglycemia and hypoglycemia and the use of excessive insulin. Hepatic glycogenosis occurs in patients with poorly controlled insulin-dependent type I or type II diabetes. The clinical manifestations of this phenomenon may include abdominal pain and obstructive symptoms such as early satiety, nausea, and vomiting. Ascites has rarely been reported. The typical biochemical findings are mildly to moderately elevated aminotransferases, with or without mild elevations of alkaline phosphatase. Liver synthetic function is usually normal. All these abnormalities, including the hepatomegaly, are readily reversible with sustained euglycemic control. The other major cause of hepatomegaly in patients with diabetes is steatosis. This is a function of the body habitus and state of insulin resistance rather than glycemic control. However, the distinction between steatosis and glycogenosis is important: whereas steatosis may progress to fibrosis and cirrhosis, glycogenosis does not, but reflects the need for better diabetic control. Glycogenosis and steatosis cannot be distinguished reliably on ultrasound examination. The histology, however, is definitive. In glycogenosis, as in primary glycogen storage diseases, there is excess glycogen in the cytoplasm, and often also in the nucleus, of hepatocytes. The hepatocytes throughout the lobule appear pale and swollen with clearly defined cell boundaries. Ultrastructural examination reveals cytoplasmic glycogen in clumps displacing organelles to the periphery of the cell, and there is little if any steatosis. We have shown that hepatomegaly due to glycogenosis in adults with diabetes is similar in all respects to the condition seen in children. As in children, liver enzyme abnormalities are unreliable in predicting the presence or the extent of glycogenosis. Hepatic glycogenosis can occur at any age, and therefore should be included in the differential diagnosis of hepatomegaly in all insulin-requiring diabetics.

Intractable cough and abnormal pulmonary function in benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis (BRIC) is a syndrome characterized by recurrent episodes of cholestasis with associated pruritus. The intensity and duration of cholestatic episodes, and the length of the intervening periods, vary unpredictably. We report the case of a patient with BRIC who was incapacitated by a severe intractable cough that accompanied marked pruritus during her second cholestatic episode. No cause for the cough was found, and it resolved spontaneously with amelioration of mild restrictive abnormalities of pulmonary function as the cholestasis subsided. Although cough has not been recognized as a complication of cholestasis, we postulate that it may occur either (i) as a result of direct stimulation of sensory nerves by circulating humoral substances related to the cholestasis that act either peripherally in the airways or centrally, or (ii) through stimulation of the vagus nerve in the liver, leading to cough that is mediated either centrally or by reflex.

Primary lymphoma of the gallbladder; case report and review of the literature.

The term extranodal lymphoma refers to lymphoma arising in tissues other than lymph nodes or major lymphoid organs (1). The GI tract is commonly involved by lymphoma. Although lymphomas of the liver and the biliary tree are uncommon, they are well described in the literature. However, there are only nine cases of primary lymphoma of the gallbladder reported in the English literature. We report a patient with primary gallbladder lymphoma diagnosed preoperatively by ultrasound, with disease confined to the gallbladder on pathology specimens and radiological examination. His rapid disease progression to diffuse abdominal involvement in 6 wk points to the importance of a timely diagnosis. We postulate that delays in making the diagnosis may lead to the underdiagnosis of primary lymphoma of the gallbladder.