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Duel Blood Supply of Liver

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hepatic portal vein and hepatic arteries.

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hepatic portal vein

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carries venous blood drained from the gastrointestinal tract

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hepatic arteries

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supply arterial blood to the liver

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Liver functions

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produces many substances (synthesis) and which maintains the balance many nutrients (homeostasis).

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excretory function

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Our body makes many waste products (such as bilirubin) which can be excreted only by the liver

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defense mechanisms

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The liver strategic placement between the gut and the rest of our body permits it to acts as a filter and prevents the passage of bacteria from the gut

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Liver disease is categorized both by

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cause and the effect it has on the liver

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Causes

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include infection, injury, exposure to drugs or toxic compounds, autoimmune processes, or a genetic defect.

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Causes of Liver disease can lead to

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hepatitis, cirrhosis, stones that develop forming blockages, fatty liver, and in rare instances liver cancer

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Genetic defects

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can prevent vital liver functions and lead to the deposition and build-up of damaging substances, such as iron or copper

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how does bilirubin get to the liver

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Bilirubin is transported to the liver is association with albumin, rapidly taken up by the hepatocytes by a carrier mediated active transport process and bound intracellularly to mostly ligandin and Z protein.

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What is bilirubin conjugated to

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glucuronic acid to produce bilirubin diglucuronide which isthen excreted into the bile.

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lower intestinal tract the three urobilinogens are spontaneously oxidized to

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stercobilin, mesobilin, and urobilin, which are the orange-brown pigment of the stool.

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Unconjugated

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Bilirubin which has not be conjugated with glucuronic acid. This form represents pre-liver processed complex. It is lipid but not water soluble

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Conjugated

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Bilirubin which has been conjugated with glucuronic acid. This form represents post-liver processed complex. It is water soluble.

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Crigler-Najjar Syndrome-

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rare genetic disorder which has a lower than normal hepatic bilirubin uridine diphosphate glucuronyltransferase (UDP-glucuronyltransferase) activity

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Gilberts Syndrome

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as heterogeneous condition usually ascribed to a decreased UDP-glucuronyltransferase activity

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Crigler-Najjar Syndrome and Gilberts Syndrome

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bilirubin cannot be conjugated at the normal rate, the rate of excretion of bilirubin is significantly reduced, and the serum concentration of unconjugated bilirubin increases.

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Unconjugated Hyperbilirubinemia

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newborn jaundice total serum bilirubin level above 5 mg per dL (86 µmol/L

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Association with disease Hyperbilirubinemia

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newborn period can be associated with severe illnesses such as hemolytic disease, metabolic and endocrine disorders, anatomic abnormalities of the liver, and infections

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Kernicterus

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refers to the neurologic consequences of the deposition of unconjugated bilirubin in brain tissue.

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bilirubin level is above 25mg/dL (428 µmol/L).

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bilirubin toxicity

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Unconjugated Hyperbilirubinemia Treatment

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Phototherapy, Exchange Transfusion

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Phototherapy

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employs blue wavelengths of light to alter unconjugated bilirubin in the skin

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Exchange Transfusion

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removes partially hemolyzed and antibody-coated erythrocytes and replaces them with uncoated donor red blood cells that lack the sensitizing antigen.

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Conjugated Hyperbilirubinemia

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conjugated and unconjugated bilirubin are retained in these disorders, and a wide range of abnormal serum concentrations of each form may be observed.

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Obstruction of the biliary tree

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an increased synthesis of enzymes such as gamma-glutamyl transferase and alkaline phosphatase.

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Mechanical obstruction of the biliary tress Causes

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carcinoma of the head of the pancreas, common bile, or ampulla of Vater.

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Dubin-Johnson Syndrome

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a rare and benign genetic disorder of bilirubin excretion where the uptake and storage of bilirubin are normal but the excretion of bilirubin into the bile is markedly impaired.

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Rotor Syndrome

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A rare idiopathic form of hyperbilirubinaemia affecting both sexes, with onset shortly after birth or in childhood. It is due to a defect in the excretion of unconjugated bilirubin into the biliary craniculi with the bilirubin being absorbed into the blood and excreted in the urine. Primarily reported in patients from the Philippines.

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Prehepatic Jaundice

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causes of jaundice include hemolysis and hematoma resorption, which lead to elevated levels of unconjugated bilirubin.

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Intrahepatic Jaundice

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disorders can lead to unconjugated or conjugated hyperbilirubinemia. The conjugated bilirubin level is often elevated by alcohol, infectious hepatitis, drug reactions, and autoimmune disorders.

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Posthepatic Jaundice

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disorders also can cause conjugated hyperbilirubinemia. Gallstone formation is the most common posthepatic process that causes jaundice

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classic definition of jaundice is a serum bilirubin level

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greater than 2.5 to 3 mg per dL (42.8 to 51.3 µmol per L) in conjunction with a clinical picture of yellow skin and sclera

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First-line serum testing in a patient presenting with jaundice should include

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CBC, total and direct bilirubin, liver enzymes

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AST and ALT

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markers of hepatocellular injury

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Alkaline phosphatase and gamma-glutamyltransferase

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markers for cholestasis.

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The second-line serum investigations may include

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tests for Hepatitis A IgM antibody, Hepatitis B surface antigen and core antibody, Hepatitis C antibody, and autoimmune markers such as antinuclear, smooth muscle, and liver-kidney microsomal antibodies.

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Acute viral hepatitis

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levels of ALT to rise several thousand units per liter. Patients with acute alcoholic hepatitis have AST and ALT levels that rise to several hundred units per liter

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alcohol-induced damage

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ratio of AST to ALT is usually greater than 1

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ALT Levels greater than 10,000 U per L

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acute injury to the liver from another source (e.g., drugs [acetaminophen] or ischemia).

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primary biliary cirrhosis

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positive for antimitochondrial antibody

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Protein Synthesis

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primary site of plasma protein synthesis.

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Albumin

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Synthesized only by the liver

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Hypoalbuminemia

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various liver disorders and may be a consequence of decreased synthesis or distribution.

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Prealbumin

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synthesized by the liver and is a sensitive indicator of alteration in hepatic synthetic or catabolic function.

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Serum immunoglobulins

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indirectly reflect impairment of hepatocyte uptake and impairment of the reticuloendothelial system to filter incoming intestinal tract antigens from venous blood.

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Ceruloplasmin

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levels increase in liver disease such as chronic active liver diseases, biliary cirrhosis and hemochromotosis.

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haptoglobin

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low levels are seen in liver disease.

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Parenchymal liver disease

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bleeding disorders.

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Ammonia Metabolism

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Under normal circumstances most of the portal vein ammonia load is metabolized to urea in hepatocytes through the urea cycle during the first pass through the liver.

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Liver Cancer

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Hepatitis and cirrhosis

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The most common type Liver Cancer

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hepatocellular carcinoma, cancer that develops in the liver’s hepatocyte cells. According to the American Cancer Society, this type encompasses about 3 out of 4 cases of primary liver cancer.

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Hemochromatosis

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most common genetic liver disorder. It involves excess iron storage and is usually diagnosed in adults.

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Reye's Syndrome

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potentially fatal disease that causes numerous detrimental effects to many organs, especially the brain and liver.

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