Ch. 18 4-6 (Dobson) Flashcards
This is defined as a decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra- or extra-hepatic bile ducts.
Cholestasis
What is the hallmark of cholestasis?
Accumulation of green-brown plugs of bile pigment in hepatocytes and dilated canaliculi.
Hepatic bile serves two major functions, which are…
1) Emulsification of dietary fat in the lumen of the gut through the detergent action of bile salts.
2) Elimination of bilirubin, excess cholesterol, xenobiotics, trace metals, and other waste products that are insufficiently water-soluble to be excreted into urine.
________ is a toxic end product of heme degradation that is processed by the liver and excreted in the bile.
Bilirubin
The majority of bilirubin produced daily is derived from breakdown of senescent _______ by macrophages in the spleen, liver, and bone marrow.
RBCs
Hepatic handling of bilirubin involves uptake from the circulation, intracellular storage, conjugation with _______ _______, and excretion into bile.
Glucuronic acid
Total serum bilirubin levels in the normal adult vary between 0.3 and 1.2 mg/dL. _________ becomes evident when the serum bilirubin levels rise above 2 to 2.5 mg/dL.
Jaundice
What are the types of bilirubin?
Unconjugated (Indirect)
Conjugated (Direct)
Testing for conjugated and unconjugated plasma bilirubin helps determine the cause of hyperbilirubinemia. Excess bilirubin production (ie, due to hemolytic anemia or ineffective erythropoiesis) or defective conjugation (due to immaturity or hereditary causes) leads to the accumulation of _________ bilirubin.
Unconjugated
This form of bilirubin is largely insoluble and cannot be excreted in the urine.
Unconjugated
Although most unconjugated bilirubin is tightly bound to ________ in the blood, at excessive levels the unbound fraction rises and may diffuse into tissues, particularly the brain in infants, producing neurologic damage known as ________.
Albumin
Kernicterus
_________ hyperbilirubinemia most often results from hepatocellular disease, bile duct injury, and biliary obstruction.
Conjugated
This form of bilirubin is water-soluble and loosely bound to serum albumin, so it can be excreted in the urine.
Conjugated
Elevated bilirubin becomes clinically evident as yellow discoloration of the skin, called _______, and sclera, called _______.
Jaundice
Icterus
Other manifestations of cholestatic disease include pruritus, skin ________ (focal accumulation of cholesterol), or symptoms related to intestinal malabsorption, including deficiencies of fat-soluble vitamins.
Xanthomas
These are the characteristic laboratory findings of cholestatic disease. The enzymes are present on the apical (canalicular) membranes of hepatocytes and bile duct epithelial cells.
Elevated serum ALP
Elevated GGT
In physiologic jaundice of the newborn, levels of _______, the enzyme responsible for bilirubin glucuronidation, are low at birth and do not reach adult levels until 3-4 months of age.
UGT1A1
Breastfeeding of a newborn may exacerbate unconjugated hyperbilirubinemia, possibly because of the presence of what enzymes in breast milk?
Bilirubin-deconjugating enzymes
In most infants, what is the treatment to keep unconjugated bilirubin within a safe range? How does it work?
Phototherapy with blue light, which converts bilirubin to a soluble isomer that is readily excreted in the urine.
This disease is autosomal recessive and contains mildly low UGT activity. This results in increased unconjugated bilirubin. Overall patients usually don’t have problems, but they can develop jaundice during times of stress like during an infection.
Gilbert Syndrome
This disease has an absence of UGT, resulting in increased unconjugated bilirubin. Results in kernicterus and is usually fatal.
Crigler-Najjar Syndrome I
***Type II has decreased UGT, very similar to Gilbert!
This is an autosomal recessive disease that is due to a deficiency of bilirubin canalicular transport protein. There is a mutation in the protein MRP2. This causes increased conjugated bilirubin. It is not clinically significant but there is deposition of brown-black melanin-like pigment in the hepatocytes and can lead to blackening of the liver.
Dubin-Johnson Syndrome
***Liver conjugates the bilirubin but can’t move it anywhere!
This disease is similar to Dubin-Johnson but does NOT have the blackening of the liver.
Rotor Syndrome
This disease causes inflammation that disrupts hepatocytes and small bile ductules, causing both conjugated and unconjugated bilirubin to increase. The urine is dark due to increased urine bilirubin, but urine urobilinogen is normal or decreased.
Viral hepatitis