Lecture 10 - Bilirubin Metabolism and secretion (Sanchez) Flashcards
icterus (jaundice)
bilirubin is an orange/reddish pigment that imparts a yellow color to tissues in which it has accumulated - this is called icterus or jaundice
what keeps bilirubin in solution in blood
its adsorption binding to plasma proteins - primarily albumin
how is bilirubin formed
as a breakdown product of tetrapyrolles that function as electron transport pigments.
what is the biggest source of bilirubin?
normal degradation of hemoproteins most of which are derived from hemoglobin
reticuloendothelial system
where released hemoglobin is split into heme and globin
what happens when the heme ring from hemoglobin is split?
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.
what is biliverdin?
an intensely green pigment which colors bile of herbivores and chickens
what happens to unconjuaged bilirubin?
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
what absorbs free bilirubin?
hepatocytes in the liver
what happens to bilirubin at the sinusoidal, basolateral membrane of the hepatocyte?
dissociation between albumin and bilirubin where bilirubin is transferred to ligandin.
is bilirubin uptake a carrier-mediated process?
yes!
what happens after bilirubin is uptaken?
it is conjugated to glucuronides by uridine diphosphate-glucuronosyltransferase
is conjugated bilirubin hydrophilic or hydrophobic?
hydrophilic
what is the rate-limiting step of bilirubin excretion?
when conjugated bilirubin is secreted actively into bile by a canalicular membrane protein against a steep concentration gradient
what happens to conjugated bilirubin in the intestinal tract?
it is poorly absorbed and is converted by microbes to urobilinogen and stercobilin.
what happens to urobilinogen in the intestinal tract
it is absorbed and enters the enterohepatic circulation
what happens to urobilinogen after it is exposed to air?
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
what is the main causes of hyperbilirubinemia?
increased production of bilirubin (typically caused by hemolysis)
impaired hepatic uptake or conjugation of bilirubin
impaired excretion of bilirubin
what happens with acute hemolysis?
red cells are rapidly degraded, overwhelming the liver’s capcity for excretion, hence a high proportion of free (or unconjugated) bilirubin.
what typically happens to the urate of urobilinogen formation in hemolytic diseases
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)
what happens when bilirubin excretion is impaired due to biliary obstruction?
what happens when it cannot be excreted properly?
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.
what does fasting do to bilirubin?
fasting reduces hepatic excretion of bilirubin.
what is unique about the horse with regards to bilirubin levels and fasting?
fasting will raise the plasma bilirubin concentration above normal and cause clearly icteric mucous membranes
