Portal cirrhosis

The serum bile salt concentration ratio in patients with portal cirrhosis or other types of hepatic cell injury has some usefulness, therefore, in the differential diagnosis of jaundice. Jaundiced patients with a bile salt concentration ratio of less than 1 will more likely be jaundiced because of hepatic cell injury, whereas those with a ratio greater than 1 will more likely be jaun- 

TABLE V. Comparison of Average Serum Concentrations of Bile Salts, Bilirubin, and Alkaline Phosphatase for Groups of Patients with Various Hepatobiliary Disorders 

Disease No. Trihy-patients droxy Dihy- droxy Total Ratio tri/di bilirubin (mg %) phosphatase (KA units) 

Although useful in diagnosis, the concentration ratio is perhaps more helpful in revealing the extent of liver injury. Jaundiced patients with a concentration ratio of less than 1 are more likely to have other evidence of extensive liver injury such as hypoalbuminemia, 3+ to 4-f cephalin flocculation, and increased serum immunoglobulin concentrations. Patients with impending or actual hepatic coma often have only chenodeoxycholate detectable in their serum, and all have had ratios of less than 1. A concentration ratio of less than I is by no means an irreversible event. Acute alcoholic liver injury is the most common example of its reversibility. When such patients are admitted to the hospital, their concentration ratio is frequently less than 1 but reverts to higher values with abstinence from alcohol, rest, good diet, and time (50). 

The primary bile salt concentration ratio also has prognostic significance in patients with chronic liver disease, since it is related to the extent of liver injury. Patients with a ratio of less than 1 usually have other evidence of 

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Tissue reserves of retinoids in the healthy adult are sufficiently large to require long-term dietary deprivation to induce deficiency. Vitamin A deficiency occurs more commonly in chronic diseases affecting fat absorption, such as biliary tract or pancreatic insufficiency, sprue, Crohn s disease involving the terminal ileum, and portal cirrhosis deficiency may also occur following partial gastrectomy or during extreme, chronic dietary inadequacy. 

Ricketts, W.E., Kirsner, J.B., Palmer, W.L., Sterling, K. Observations on the diagnostic value of liver biopsy, tests of hepatic function, and electrophoretic fractionation of serum proteins in asymptomatic portal cirrhosis. J. Lab. Clin. Med. 1950 35 403-407... 

Grinnell, R. Omentopexy in portal cirrhosis of the liver with ascites. A review of twenty-three cases. Ann. Surg.1935 101 891 -901... 

Polyclonal increases in serum immunoglobulins are the normal response to infections. IgG response predominates in autoimmune responses IgA in skin, gut, respiratory, and renal infections and IgM in primary viral infections and bloodstream parasites, such as malaria. Chronic bacterial infections may cause an increase in serum levels of all immunoglobulins. In such cases, estimations of the individual immunoglobulins seldom provide more information than protein electrophoresis. They are of value, however, in the differential diagnosis of liver disease and of intrauterine infections. In primary biliary cirrhosis, the IgM level is greatly increased in chronic active hepatitis, IgG and sometimes IgM are increased and in portal cirrhosis, IgA and sometimes IgG are increased. In intrauterine infections, production of IgM by the fetus increases, and the IgM level in umbilical cord blood is increased. Estimations of IgE are used in the management of asthma and other allergic conditions, especially in children. 

Hepner G, Vesell E. Assessment of aminopyrine metabolism in man by breath analysis after oral administration of " C-aminopyrine. Effects of phe-nobarbital, disulfiram and portal cirrhosis. N Engl J Med 1974 291 1384-8. 

Elevated serum copper and ceruloplasmin levels were recorded in various forms of acute and chronic liver disease (BIO, G13, G17, P6, R2, R6, R14, S9). In a group of patients with portal cirrhosis the serum non-ceruloplasmin-bound copper was also elevated (G13). The elevation of serum copper and ceruloplasmin is most marked in biliary cirrhosis and, generally... 

Fig. 5. Serum bile salt concentration ratios are plotted by disease group. The group with bile duct obstruction, whether intra- or extrahepatic, tends to have a higher ratio (greater than 1) than the portal cirrhosis group, in which the ratio is usually greater than 1 (see text for details).

Portal cirrhosis Viral hepatitis Bile duct disease... 

The ammonia produced by enteric bacteria and absorbed into portal venous blood and the ammonia produced by tissues are rapidly removed from circulation by the liver and converted to urea. Only traces (10—20 Ig/dL) thus normally are present in peripheral blood. This is essential, since ammonia is toxic to the central nervous system. Should portal blood bypass the liver, systemic blood ammonia levels may rise to toxic levels. This occurs in severely impaired hepatic function or the development of collateral links between the portal and systemic veins in cirrhosis. Symptoms of ammonia intoxication include tremor, slurred speech, blurred vision, coma, and ultimately death. Ammonia may be toxic to the brain in part because it reacts with a-ketoglutarate to form glutamate. The resulting depleted levels of a-ketoglutarate then impair function of the tricarboxylic acid (TCA) cycle in neurons. 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Describe the epidemiology and social impact of portal hypertension and cirrhosis. 

O Portal hypertension is the precipitating factor for the complications of cirrhotic liver disease—ascites, spontaneous bacterial peritonitis (SBP), variceal bleeding, and hepatic encephalopathy. Lowering portal pressure can reduce the complications of cirrhosis and decrease morbidity and mortality. 

Cirrhosis is the progressive replacement of normal hepatic cells by fibrous scar tissue. This scarring is accompanied by the loss of viable hepatocytes, which are the functional cells of the liver. Progressive cirrhosis is irreversible and leads to portal hypertension that is in turn responsible for many of the complications of advanced liver disease. These consequences include (but are not limited to) spontaneous bacterial peritonitis (SBP), hepatic encephalopathy, and variceal bleeding.1... 

FIGURE 19-1. The portal venous system. (From Timm EJ, Stragand JJ. Portal hypertension and cirrhosis. In DiPiro JT, Talbert RL, Yee GC, et al, (eds.) Pharmacotherapy A Pathophysiologic Approach. 6th ed. New York McGraw-Hill 2005 694, with permission.)... 

Portal hypertension is a consequence of increased resistance to blood flow through the portal vein. Increased resistance is usually due to restructuring of intrahepatic tissue (sinusoidal damage) but may also be caused by presinusoidal damage such as portal vein occlusion from trauma, malignancy, or thrombosis. A third (and the least common) mechanism is outflow obstruction of the hepatic vein. This latter damage is posthepatic, and normal liver structure is maintained. This chapter will focus on portal hypertension caused by intrahepatic damage from cirrhosis. 

Sinusoidal damage from cirrhosis is the most common cause of portal hypertension. The sinusoids are porous vessels within the liver that surround radiating rows of hepatocytes, the basic functional cells of the liver (Fig. 19-2). Progressive destruction of hepatocytes and an increase in fibroblasts and connective tissue surrounding the hepatocytes culminate in cirrhosis. Fibrosis and regenerative nodules of scar tissue... 

The sinusoids transport both portal and arterial blood to the hepatocytes. The systemic blood delivered to the liver contains nutrients, drugs, and ingested toxins. The liver processes the nutrients (carbohydrates, proteins, lipids, vitamins, and minerals) for either immediate use or for storage, while the drugs and toxins are metabolized through a variety of processes known as first-pass metabolism. The liver also processes metabolic waste products for excretion. In cirrhosis, bilirubin (from the enzymatic breakdown of heme) can accumulate this causes jaundice (yellowing of the skin), scleral icterus (yellowing of the sclera), and tea-colored urine (urinary bilirubin excretion). 

The pathophysiologic mechanisms of portal hypertension and of cirrhosis itself are entwined with the mechanisms of ascites (Fig. 19-3). Cirrhotic changes and the subsequent decrease in synthetic function lead to a decrease in production of albumin (hypoalbuminemia). Albumin is the major intravascular protein involved in maintaining oncotic pressure in the vascular system low serum albumin levels and increased capillary permeability allow fluid to leak from the vascular space into body tissues. This can result in peripheral edema, ascites, and fluid in the pulmonary system. The obstruction of hepatic sinusoids and... 

Clinical Presentation of Cirrhosis and Complications of Portal Hypertension... 

Drug therapy for portal hypertension and cirrhosis can alleviate symptoms and prevent complications but it cannot reverse cirrhosis. Drug therapy is available to treat the complications of ascites, varices, spontaneous bacterial peritonitis, hepatic encephalopathy, and coagulation abnormalities. 

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