Ascites

The word ascites is of Greek origin (askos) and means bag or sac. Ascites describes the condition of pathologic fluid accumulation within the abdominal cavity. Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle. This article focuses only on ascites associated with cirrhosis.

The accumulation of ascitic fluid represents a state of total-body sodium and water excess, but the event that initiates the unbalance is unclear. Three theories of ascites formation have been proposed.

The underfilling theory suggests that the primary abnormality is inappropriate sequestration of fluid within the splanchnic vascular bed due to portal hypertension and a consequent decrease in effective circulating blood volume. This activates the plasma renin, aldosterone, and sympathetic nervous system, resulting in renal sodium and water retention.

The overflow theory suggests that the primary abnormality is inappropriate renal retention of sodium and water in the absence of volume depletion. This theory was developed in accordance with the observation that patients with cirrhosis have intravascular hypervolemia rather than hypovolemia.

The most recent theory, the peripheral arterial vasodilation hypothesis, includes components of both of the other theories. It suggests that portal hypertension leads to vasodilation, which causes decreased effective arterial blood volume. As the natural history of the disease progresses, neurohumoral excitation increases, more renal sodium is retained, and plasma volume expands. This leads to overflow of fluid into the peritoneal cavity. According to the vasodilation theory, the underfilling theory is proposed to be operative early and the overflow theory is proposed to be operative late in the natural history of cirrhosis.

Although the sequence of events that occurs between the development of portal hypertension and renal sodium retention is not entirely clear, portal hypertension apparently leads to an increase in nitric oxide levels. Nitric oxide mediates splanchnic and peripheral vasodilation. Patients with ascites have greater hepatic artery nitric oxide synthase activity compared to patients without ascites.

Regardless of the initiating event, a number of factors contribute to the accumulation of fluid in the abdominal cavity. Elevated levels of epinephrine and norepinephrine are well-documented factors. Hypoalbuminemia and reduced plasma oncotic pressure favor the extravasation of fluid from the plasma to the peritoneal fluid, and, thus, ascites is infrequent in patients with cirrhosis unless both portal hypertension and hypoalbuminemia are present.

Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate of 50%. The development of refractory ascites carries a poor prognosis, with a 1-year survival rate of less than 50%.

Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle.

Collagenous and Lymphocytic Colitis

Collagenous colitis (CC) was described concurrently in 1976 by Lindstrom and by Freeman. In 1980, Read described microscopic colitis, which is clinically indistinguishable from CC but is differentiated from it by colonic biopsy features. Later, the term lymphocytic colitis (LC) was proposed by Lazenby to replace the term microscopic colitis and to distinguish it from infectious colitis and inflammatory bowel disease (ulcerative colitis and Crohn disease). The term microscopic colitis is now used to describe both CC and LC, and these conditions should be considered in any patient with unexplained nonbloody diarrhea. Patients undergoing either sigmoidoscopy or colonoscopy for unexplained diarrhea who have normal endoscopic findings should have biopsy samples taken to diagnose or rule out either form of microscopic colitis.

LC and CC are relatively rare conditions that are diagnosed when a patient with chronic watery nonbloody diarrhea has an endoscopically or radiographically normal colon, but colonic biopsies show unique inflammatory changes. Because the mucosa is not ulcerated or otherwise disrupted, the diarrhea generally does not contain blood or pus.

• The characteristic feature of LC is an infiltration of lymphocytes into the colonic epithelium. CC shares this feature but additionally shows a distinctive thickening of the subepithelial collagen table. LC and CC have been suggested to represent different phases of a single pathophysiologic process, with LC possibly being a precursor or earlier phase of CC; however, this has not been proven.

• The diarrhea in CC is more likely due to the inflammatory process than to the subepithelial collagen layer, although this layer may serve as a cofactor in the role of a diffusion barrier.

• Increased levels of immunoreactive prostaglandin E2 in stool water may contribute to a secretory diarrhea.

• Some patients with CC and concurrent collagenous infiltration of the duodenum and/or the ileum have demonstrated altered small bowel dysfunction, demonstrated by reduced D-xylose absorption.

• Some individuals have bile acid malabsorption demonstrated by the Se-75-homotaurocholate (SeHCAT) test, in which a positive test result is shown by retention of less than 11% of the administered dose of radioactivity after 7 days.

• Some patients with CC may have increased mucosal secretion of vascular endothelial growth factor, a fibrosis-enhancing peptide.

United States

True incidence is not known. The disease has been increasingly diagnosed over the past 20 years, but it is still uncommon. A recently published population-based study found the incidence of microscopic colitis to increase significantly from 1.1 per 100,000 persons in the late 1980s to 19.6 per 100,000 persons by the end of 2001. Rates increased with age. Prevalence at the end of the study period was 103.0 per 100,000 persons (39.3 for CC and 63.7 for LC).

Morbidity is limited to the consequences of diarrhea and malabsorption, including metabolic abnormalities such as hypokalemia and dehydration, weight loss, fatigue, and vitamin deficiencies. This is not considered a life-threatening condition; however, profuse watery diarrhea may lead to severe dehydration and electrolyte abnormalities requiring intensive resuscitation.

LC affects similar numbers of men and women, while CC is up to 20 times more frequent in women than in men.

Both conditions are observed most commonly in people older than 40 years, with peak incidence in the sixth and seventh decades of life, and the incidence of both conditions increases with age. Isolated cases have been reported in younger populations, including children.

Hirschsprung Disease

Hirschsprung disease is a developmental disorder of the enteric nervous system and is characterized by an absence of ganglion cells in the distal colon resulting in a functional obstruction. Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century when Whitehouse and Kernohan described the aganglionosis of the distal intestine as the cause of obstruction in their series of patients (Whitehouse, 1948). In 1949, Swenson described the first consistent definitive procedure for Hirschsprung disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have been described, including the Duhamel and Soave techniques. More recently, advances in surgical technique, including minimally invasive procedures, and earlier diagnosis have resulted in decreased morbidity and mortality for patients with Hirschsprung disease.

Most cases are now diagnosed in the newborn period. Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours after birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard. Once the diagnosis is confirmed, the basic treatment is to remove the poorly functioning aganglionic bowel and create an anastomosis to the distal rectum with the healthy innervated bowel (with or without an initial diversion).

Congenital aganglionosis of the distal bowel defines Hirschsprung disease. Aganglionosis begins with the anus, which is always involved, and continues proximally for a variable distance. Both the myenteric (Auerbach) and submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function. The precise mechanism underlying the development of Hirschsprung disease is unknown.

Enteric ganglion cells are derived from the neural crest. During normal development, neuroblasts will be found in the small intestine by the 7th week of gestation and will reach the colon by the 12th week of gestation (Okamoto, 1967). One possible etiology for Hirschsprung disease is a defect in the migration of these neuroblasts down their path to the distal intestine. Alternatively, normal migration may occur with a failure of neuroblasts to survive, proliferate, or differentiate in the distal aganglionic segment. Abnormal distribution in affected intestine of components required for neuronal growth and development, such as fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors, may be responsible for this theory (Gaillard, 1982; Langer, 1994; Tosney, 1986).

Additionally, the observation that the smooth muscle cells of aganglionic colon are electrically inactive when undergoing electrophysiologic studies also points to a myogenic component in the development of Hirschsprung disease (Kubota, 2002). Finally, abnormalities in the interstitial cells of Cajal, pacemaker cells connecting enteric nerves and intestinal smooth muscle have also been postulated as an important contributing factor (Ward, 2001; Vanderwinden, 1996).

Three neuronal plexus innervate the intestine: the submucosal (ie, Meissner) plexus, the intermuscular (ie, Auerbach) plexus, and the smaller mucosal plexus. All of these plexus are finely integrated and involved in all aspects of bowel function, including absorption, secretion, motility, and blood flow.

Normal motility is primarily under the control of intrinsic neurons. Bowel function is adequate, despite a loss of extrinsic innervation. These ganglia control both contraction and relaxation of smooth muscle, with relaxation predominating. Extrinsic control is mainly through the cholinergic and adrenergic fibers. The cholinergic fibers cause contraction, and the adrenergic fibers mainly cause inhibition.

In patients with Hirschsprung disease, ganglion cells are absent, leading to a marked increase in extrinsic intestinal innervation. The innervation of both the cholinergic and adrenergic systems is 2-3 times that of normal innervation. The adrenergic (excitatory) system is thought to predominate over the cholinergic (inhibitory) system, leading to an increase in smooth muscle tone. With the loss of the intrinsic enteric inhibitory nerves, the increased tone is unopposed and leads to an imbalance of smooth muscle contractility, uncoordinated peristalsis, and a functional obstruction.

Ogilvie Syndrome

Ogilvie syndrome, or acute colonic pseudo-obstruction (ACPO), is a clinical disorder with the signs, symptoms, and radiographic appearance of an acute large bowel obstruction with no evidence of distal colonic obstruction. The colon may become massively dilated; if not decompressed, the patient risks perforation, peritonitis, and death.

In 1948, Sir Heneage Ogilvie described 2 patients with metastatic cancer and retroperitoneal spread to the celiac plexus. The patients also had signs and symptoms of colonic obstruction but with no evidence of organic obstruction to the intestinal flow. Ogilvie hypothesized that the etiology of their conditions was an imbalance in the autonomic nervous system with sympathetic deprivation to the colon leading to unopposed parasympathetic tone, regional contraction, and, thus, a functional obstruction.

In 1958, Dudley et al used the term pseudo-obstruction to describe the clinical appearance of a mechanical obstruction with no evidence of organic disease during laparotomy.

PATOFISIOLOGI

The pathophysiology of ACPO is not clearly understood. Research into the neurophysiology of the colon reveals that Ogilvie's hypothesis was close to the proposed current understanding. The parasympathetic nervous system is responsible for stimulating gut motility. The vagus nerve supplies the parasympathetic tone from the upper GI tract to the splenic flexure, and the sacral parasympathetic nerves (S2 to S5) supply the left colon and rectum. Sympathetic stimuli result in the inhibition of bowel motility and contraction of sphincters. The lower 6 thoracic segments supply the sympathetic tone to the right colon, while lumbar segments 1-3 supply the left colon.

Based on evidence from pharmacologic studies, metabolic abnormalities, retroperitoneal trauma, and various spinal blockade studies, an imbalance in the autonomic innervation appears to lead to a functional bowel obstruction. Unlike Ogilvie's hypothesis, some current evidence suggests that an interruption of the sacral parasympathetic nerves occurs, leading to an adynamic distal colon that is similar to Hirschsprung disease, except with normal ganglion cells observable on autopsy. Other research supports the belief that the sympathetic tone increases in these patients, who usually are very ill, leading to inhibition of colonic motility.

The cecum is the usual site of the largest dilatation in patients with ACPO and is thus prone to the greatest risk of perforation. The Laplace law indicates that the intraluminal pressure needed to stretch the wall of a hollow tube is inversely proportional to its diameter. The largest diameter in the colon is the cecum; therefore, the cecum requires the smallest amount of pressure to increase in size and to thus increase wall tension. As the wall tension of the colon increases, ischemia with longitudinal splitting of the serosa, herniation of the mucosa, and perforation can occur.

Buyer beware of psychiatric genetic tests

You can now buy a commercial genetic test that claims to assess your risk of developing bipolar disorder. Genetic tests for major depression and schizophrenia are also expected to reach the market soon. However, although the suspects are numerous, the genes responsible for most brain disorders remain unknown. So, when it comes to commercial genetic tests, we just don’t know enough to make the tests useful, reports the May issue of the Harvard Mental Health Letter.
One problem is that the genetics field is advancing so rapidly that it’s hard to keep up with developments, never mind figure out which ones are clinically relevant. Most experts also believe that psychiatric disorders develop because of the interplay between multiple genes, each exerting small effects. That makes finding the responsible genes harder. Further complicating matters, research has revealed that many healthy relatives of people with psychiatric disorders have risk genes. Whether a person develops an illness depends on unknown ways the risk genes interact with other genes and environmental factors.

Scientists have identified perhaps thousands of candidate genes that may contribute to psychiatric conditions. But experts continue to debate which genes are actually involved. Most candidate genes fail to hold up—meaning that the association between the gene and a given illness disappears when scientists try to replicate the results. One analysis estimated that 70% to 80% of candidate genes are false positives.

Dr. Michael Miller, editor in chief of the Harvard Mental Health Letter,notes that someday it may be possible to reliably assess risk for psychiatric disorders. But at this point, the technology—and the science—is still evolving.

On the prevention of myopia

I was astonished to read that still today one can question the development of myopia when working in dim light (1). The extra accomodation strain that it causes on the reading eye is indisputable. Suboptimal lighting, however, is only a minor factor in the development of myopia. The constant haste combined with vast close-work in the modern society maintain accomodation stress that often leads to accomodation spasm. Thus the present prevention of myopia is a global disgrace. It has been allowed to be continued unchanged for the past 100 years!

The old beliefs of myopia being inherited hinder the acceptance of the fact based on practical experience that this is not the case.

The most important way to counteract the development of myopia is if a child as early as possible would use reading glasses (+3.0, possibly as add to the plus-distant correction) in all close work. In the case that myopia already has developed it is of uttermost importance to avoid close work with distant correction. Bifocals with significant plus addition is the method of choice.

In year 1972 I published Tetralogia (2), which arosed severe resistance among my Finnish colleagues. Tetralogia deals with accommodation strain leading to accommodation spasm and pseudomyopia and the prevention of myopia. I have developed polyphasic fogging method for revealing the spasm of accomodation (3). I stressed also the clinical significance, which accommodation strain has to our organism as a whole (2,4).

From the year 1973 Donald S Rehm has handled the same theme. As the President of International Myopia Prevention Association he, in year 2005, wrote a petition to FDA, which became rejected (5). It is sad to see, that all the leading American Institutions have done everything in their power to hide this knowledge from the parents and to retain the business of minusglasses and the billions- bringing operative activity of healthy corneas. Quoting President Rehm if professionals “had any concern for the people of the world they could expose and end this tragedy almost overnight”.

For an ophthalmologist it is impossible to think that a professional on the eyebranch would not understand this much about the physiology of accommodation. Is this unconcernedness thus a question of conscious denying of the truth or is this all about the money?

Blood-Thinner No Help for Dialysis Treatment

TUESDAY, May 13 (HealthDay News) -- A major trial has dashed the hope that the clot-preventing drug Plavix could help in the delicate balancing act needed to establish a blood vessel suitable for dialysis for kidney patients.

Giving Plavix (clopidogrel) did reduce the risk that a blood clot would block the vessel created by combining a vein and an artery, a standard procedure for kidney dialysis. But adding the clot-preventing drug did not increase the number of fistulas, as they are called, that could be used for artificial kidney treatment over the long run, the study authors reported.

The study was done because "early thrombosis [blood clotting] is one of the major causes of fistula failure," said Dr. Laura M. Dember, an associate professor of medicine at Boston University, and lead author of the report.

"What we found was that despite the reduction in thrombosis that was clear enough, there was an equal proportion of fistula failure," Dember said. "What is ultimately important is the usability of the fistula for dialysis."

The researchers published their findings in the May 14 issue of the Journal of the American Medical Association.

About 470,000 Americans have kidney failure and are kept alive by dialysis, in which their blood is run through a machine that filters out impurities. The preferred technique for linking to the artificial kidney is to create a fistula, which has lower rates of thrombosis -- blockage -- and infection than alternatives such as synthetic artery-vein grafts. But many fistulas never mature enough to allow dialysis.

The multi-center trial included 877 people with total or partial kidney failure who underwent surgery to create a fistula. Half were given Plavix for six weeks after the surgery, while the other half were not.

Plavix did reduce the risk of blockage by 37 percent over the six-week period. Among the 866 people who were tested, 12.2 percent of those given Plavix had a blockage, compared to 19.5 percent of those not given the anti-clotting drug.

But Plavix therapy did not reduce the incidence of cases in which the fistula could not be used for dialysis, which was 61.8 percent in those getting the drug and 59.5 percent in those getting a placebo.

The rate of fistula failure was about 50 percent higher than anticipated, Dember said, and that might have an effect on future practice.

"There has been an increased emphasis on trying to create fistulas in as many patients as possible," she said. "So, the criteria have changed. We need to develop better methods for selecting suitable candidates for fistula creation."

The trial also indicated the direction that that research should take, Dember said.

"Our future efforts should be directed at understanding the basic mechanisms of fistula maturation," she said. "If we better understand those mechanisms, we should be able to identify maturity-enhancing interventions.