ePathoPlusPage

Liver Dysfunction

Outline

A. Jaundice
        1. by itself  jaundice is completely harmless (except in neonates) but it
         always is a manifestation of hematopoietic or biliary disease

        2. normal bilirubin metabolism

a. the rbc's are broken down in the liver or spleen and the heme (from the
             hemoglobin) is converted into biliverdin.Biliverdin is then converted into
             unconjugated bilirubin. This is insoluble and so is bound to albumin as it
             circulates through the blood. Because it is insoluble it cannot be excreted
             by the kidney

        b. hepatocytes take up unconjugated bilirubin and convert it to conjugated
              bilirubin. Some of this finds its way into the blood and it can be executed
              by the kidney because it is water soluble.( it gives the urine its            
              characteristic yellow color). Most of it becomes stored in  the gall bladder as a constituent of bile

         c. when conjugated bilirubin (in bile ) is released into the small intestine,
              special bacteria convert it into urobilongen. Urobilinogen is the pigment
              that gives stool it's characteristic brown color. Some urobilinogen finds
              its way into the blood where it can be excreted by kidneys.

          d. Summary of bilirubin products:
                1. unconjugated bilirubin - found in blood only
                2. conjugated bilirubin- some found in blood, some excreted in urine (called urine bilirubin)
                3. total bilirubin - combination of unconjugated and
                 conjugated bilirubin found in blood
                4.urobilinogen- mostly excreted in feces, some finds way into blood and excreted by urine

    3. pathophysiology of jaundice
        a. Unconjugated hyperbilirubinemia (elevation of unconjugated bilirubin)
            due to
                1.increased bilirubin production- as would occur in cases of hemolysis

2. impaired delivery of bilirubin to liver- as would occur in R sided CHF or in reaction to drugs such as salicylates, sulfonamides, rifampin

                3.decreased conjugation of bilirubin as would occur in neonatal
                    jaundice

        b. Conjugated hyperbilirubinemia (elevation of conjugated bilirubin)
            1. N.B.   cholestasis is a general term which is applied to any situation in
                 which there is an abnormality in the excretory pathway of bile

            2. due to intrahepatic cholestasis without mechanical obstruction as might
                 occur in viral hepatitis, alcoholic hepatitis, lymphomas, sickle cell Dx,
                 atresia of bile ducts

            3. due to intrahepatic cholestasis secondary to mechanical obstruction as
                 might occur in cirrhosis, metastatic liver disease

            4. cholestasis due to extrahepatic obstruction as might occur in common
                 bile duct stones, pancreatitis, parasites, stricture of common bile duct

B. Hepatitis ( an inflammation of the liver)
    a. viral hepatitis
        1. symptoms (general to all types of hepatitis)
                fatigue
                anorexia
                taste changes
                nausea
                flu like symptoms
                dark urine, clay colored stools
                jaundice

        2. liver function tests often show - ALT (formerly SGPT) and AST (formerly
             SGOT) elevated.

        3. comparison of different types of hepatitis

C. Cirrhosis
    1. term applied to disease of liver characterized by diffuse inflammation and
         fibrosis of liver tissue causing structural changes and significant loss of liver
         function.

    2. types
        a. Biliary

b. Postnecrotic

c. Cardiac

d. Laennec's (caused by alcoholism, most common in US)

3.. Stages and symptoms

a. Liver inflammation

b. liver necrosis
    1. increased portal pressure

    2. alterations in bilirubin metabolism

    3. decreased hormonal metabolism

    4. decreased protein

    5. decreased Vit K absorption and synthesis of clotting factors

c. total liver failure
     1. liver can no longer take up ammonia (breakdown product of protein)
                 and convert it into urea, so ammonia levels build up in bloodstream.
                 Ammonia can cross blood brain barrier. Leads to hepatic
                 encephalopathy

     2. Stages of hepatic encephalopathy
          a. prodromal

                  b. impending

                  c. stuporous

           d. comatose

D. Cholecystitis and Cholelithiasis   
1. cholecystitis can be either acute or chronic
     a. infection or blockage leads to inflammation- distention (can impair
                 circulation)- lead to necrosis

2. cholelithiasis
            a. may either precede or follow chronic cholecystitis

            b. three factors contribute
                1. metabolic (increased concentration of bile acids, pigment and or
                cholesterol)

        2. stasis

       3. inflammation
   

Discussion  

    Vaccines are available for Hepatitis A and B, but not for C. Anyone contemplating travel to an area of the world with poor sanitation would be well advised to be vaccinated against HAV. HBV vaccine is mandatory for health care workers and beginning for all people born in the last few years.Vaccination against HBV protects against HDV. Hepatitis C is a major health concern. About 10,000 people die of the disease each year and the numbers are increasing. The CDC estimates that there are four times as many people infected with HCV as with HIV. About 4 million Americans have HCV, i.e. 2% of the population.  It is expected that in the next 10 years the death rate from HCV will triple. When first infected with the virus, people seldom get sick immediately (as with HAV and HBV). Rather, the virus quietly damages the liver. In some cases, it may be 20 years before the symptoms appear. The only treatment available for HCV is interferon. And this treatment doesn't always work. It clears the virus from the bloodstream in only about 20% of the patients treated with it. In addition, treatment, which requires thrice weekly injections for several months, has many side effects. These side effects include flu like symptoms, depression, alopecia. It is difficult to develop a vaccine against HCV sin ce it can mutate easily. Currently there are six different genotypes and more than 30 subtypes of HCV. HCV may be present in anyone who received a blood transfusion prior to 1992. About 10% of the transmissions are unexplained, 50% are linked to IVDA., 20% to sexual transmission (multiple sex partners increases the risk) 

Clinically  

    Jaundice can occur in association with a variety of disorders. Evaluation of findings from the health history and physical exam can help aid in the differential diagnosis. Generally speaking, consider an extreme case of someone with a complete obstruction to the outflow of bile (an example of a posthepatic condition)   In this case no conjugated bilirubin enters the intestine, therefore, no urobilinogen is produced and the stool is "clay colored". Since the conjugated bilirubin is blocked from excretion into the intestine, more of it is absorbed into the bloodstream, hence the level of conjugated bilirubin is elevated (therefore, total bilirubin is also elevated) and the level of urine bilirubin is elevated, giving the urine a darker than usual color. A urinalysis reveals decreased urobilinogen in the urine.This pattern, although extreme, is typical of what is referred to as an obstructive jaundice. Consider the findings in a case of hemolytic anemia. (an example of a prehepatic condition). The major event is the increased destruction of rbc's leading to an increased production of unconjugated bilirubin. Assuming the liver is normal it increases its handling of unconjugated bilirubin, converting it into conjugated bilirubin and subsequently this is converted into urobilinogen. This increased urobilinogen shows up in the urine. There is so much unconjugated bilirubin that even though the liver is increasing its production of conjugated bilirubin, inevitably unconjugated bilirubin backs up into the blood (waiting to be processed, so to speak). Thus, the level of unconjugated bilirubin rises *therefore, the level of total bilirubin goes up). This pattern is referred to as hemolytic jaundice.