Lecture 10 - Bilirubin Metabolism and secretion (Sanchez)

Question 1

icterus (jaundice)

Answer 1

bilirubin is an orange/reddish pigment that imparts a yellow color to tissues in which it has accumulated - this is called icterus or jaundice

Question 2

what keeps bilirubin in solution in blood

Answer 2

its adsorption binding to plasma proteins - primarily albumin

Question 3

how is bilirubin formed

Answer 3

as a breakdown product of tetrapyrolles that function as electron transport pigments.

Question 4

what is the biggest source of bilirubin?

Answer 4

normal degradation of hemoproteins most of which are derived from hemoglobin

Question 5

reticuloendothelial system

Answer 5

where released hemoglobin is split into heme and globin

Question 6

what happens when the heme ring from hemoglobin is split?

Answer 6

the heme ring is split, releasing free iron and a straight chain of four pyrolle nuclei. the iron is removed for reuse and the porphyrin ring is opened giving biliverdin which is quickly reduced to free (unconjugated) bilirubin.

Question 7

what is biliverdin?

Answer 7

an intensely green pigment which colors bile of herbivores and chickens

Question 8

what happens to unconjuaged bilirubin?

Answer 8

it is gradually released from macrophages into plasma, where it is quickly bound to albumin.

Note that this bound form is still considered free (unconjugated) bilirubin

Question 9

what absorbs free bilirubin?

Answer 9

hepatocytes in the liver

Question 10

what happens to bilirubin at the sinusoidal, basolateral membrane of the hepatocyte?

Answer 10

dissociation between albumin and bilirubin where bilirubin is transferred to ligandin.

Question 11

is bilirubin uptake a carrier-mediated process?

Answer 11

yes!

Question 12

what happens after bilirubin is uptaken?

Answer 12

it is conjugated to glucuronides by uridine diphosphate-glucuronosyltransferase

Question 13

is conjugated bilirubin hydrophilic or hydrophobic?

Answer 13

hydrophilic

Question 14

what is the rate-limiting step of bilirubin excretion?

Answer 14

when conjugated bilirubin is secreted actively into bile by a canalicular membrane protein against a steep concentration gradient

Question 15

what happens to conjugated bilirubin in the intestinal tract?

Answer 15

it is poorly absorbed and is converted by microbes to urobilinogen and stercobilin.

Question 16

what happens to urobilinogen in the intestinal tract

Answer 16

it is absorbed and enters the enterohepatic circulation

Question 17

what happens to urobilinogen after it is exposed to air?

Answer 17

it is oxidized to form urobilin or stercobilin in the urine or feces.

this is what accounts for much of the golden brown color or urine or feces.

in herbivores, chlorophyll pigments in the feces mask this color, hence only the feces of neonatal herbivores have a yellow color

Question 18

what is the main causes of hyperbilirubinemia?

Answer 18

increased production of bilirubin (typically caused by hemolysis)

impaired hepatic uptake or conjugation of bilirubin

impaired excretion of bilirubin

Question 19

what happens with acute hemolysis?

Answer 19

red cells are rapidly degraded, overwhelming the liver’s capcity for excretion, hence a high proportion of free (or unconjugated) bilirubin.

Question 20

what typically happens to the urate of urobilinogen formation in hemolytic diseases

Answer 20

the rate of urobilinogen formation is increased, as is the formation of urobilin.

this is clinically apparent by an increase of urobilin in the urine (bilirubinuria)

Question 21

what happens when bilirubin excretion is impaired due to biliary obstruction?

what happens when it cannot be excreted properly?

Answer 21

free bilirubin enters the hepatic cells and is conjugated normally.

when it cannot be excreted properly, its returned to the blood stream, resulting in increased conjugated bilirubin.

Question 22

what does fasting do to bilirubin?

Answer 22

fasting reduces hepatic excretion of bilirubin.

Question 23

what is unique about the horse with regards to bilirubin levels and fasting?

Answer 23

fasting will raise the plasma bilirubin concentration above normal and cause clearly icteric mucous membranes