Flashcards in Jaundice Ebook Deck (56):
Where do liver cells first excrete bile?
What are canaliculi?
intercellular spaces between the liver cells
Where do canaliculi drain?
right and left hepatic ducts, after which bile travels via the common hepatic and cystic ducts to the gall bladder.
Function of the gallbladder?
concentrate the bile 10 fold by removing water and stores bile until a person eats
Describe the exretion of bile
Bile is discharged from the gallbladder via the cystic duct into the comon bile duct and then into the duodenum, where it begins to dissolve the fat ingested by food
Blood supply (oxygenated blood) to the gallbladder?
cystic artery and is usually a branch of the right hepatic artery. When the cystic artery reaches the neck of the gallbladder, it divides into anterior and posterior divisions
Venous supply (draining) for the gallbladder?
small veins that either directly enter into the liver, or, rarely to a large cystic vein that carries blood back to the portal
What is a HIDA scan (also called hepatobiliary scintigraphy, cholescrintigraphy, hepatobiliary scan)?
A HIDA scan is an imaging procedure that helps track the production and flow of bile from your liver to your small intestine.
Describe process of HIDA scan
Technetium-99m-labeled iinodiacetic acid analogs (new class of organic anion) are taken up and secreted by hepatocyte into hepatic bile by a carrier-mediated organic anion system. The amount of uptake and the rapidity of its elimination from the liver is dependent upon the structural configuration of the agent as well as the function integrity of the hepatocyte and the patency of the biliary system.
(essentially you are tracking the movement of a labeled molecule that mimics bile, checking for any obstruction to flow using special imaging)
Can the body metabolize cholesterol to simpler constituent (CO2, H2O, etc.)
How does the body eliminate cholesterol?
The only mechanism the body possesses to eliminate cholesterol is via the bile acids (and their derivatives, the bile salts) in the feces
What are the primary bile acids?
Cholic acid and chenodeoxycholic acid ; these are the initial products of bile-targeted cholesterol metabolism in the liver
What enzyme is the rate limiting step catalyzed by in bile synthesis?
How are bile acids different from cholesterol?
24 carbon atoms, amphipathic nature, presence of two or three -OH groups, and negative charge
How are primary bile acids further modified?
The primary bile acids are further modified with amide linkages of glycine or taurine to the ring's carboxyl group, to produce the primary bile salts, glycocolic acid and taurocholic acid
(Why make these modifications? enhance their hydrophilicity/lower pka)
Which verison of bile salts enter circulation?
The modified primary bile salts (glcocolic and taurocholic acid) enter the enterohepatic circulation
Where are the glycine and taurine residues removed? Why does this matter? How does it?
1. in the colon
2. allows for passive uptake of bile acids
3. bacteria in the gut (specifically the colon)
What is cholelithiasis?
The precipitation or crystallization of cholesterol if more cholesterol enters the bile than can be excreted
What causes cholelithiasis
caused by a decrease of bile acids in the bile
What can cause a decrease in bile acids in bile?
(1) gross malabsorptionof bile acids from the intestine; seen in patients with severe ileal disease
(2) obstruction of the biliary tract
(3) sever hepatic dysfunction, leading to decreased synthesis of bile salts, or other abnormalities in bile production
(4) excessive feedback suppresion of bile acid synthesis as a result of an accelerated rate of recycling of bile acids
Recommend treatment of asymptomatic gallstones?
Surgical treatment of asymptomatic gallstones without medically disease is discourage. Approximately 25% of patients with gallstones develop symptoms within 10 years. The risk of complications arising from interventions is higher than the risk of symptomatic disease.
(I think this is saying to not do anyting if it is asymptomatic).
When is removal of the gallbladder recommended?
Removal of the gallbladder (cholecystectomy) is generally indicated in patients who have experienced symptoms or complications of gallstones, unless the patient's age and generalhealth make the risk of surgery prohibitive.
Other options to surgurical removal?
(1) temporary drainage of pus from the gallbladder
(2) endoscopic retrograde sphinceterotomy
(a. endoscopic refers to the use of an endoscope
b. retrograde refers to the insertion of the endoscope up into the ducts in a direction opposite to or against the normal flow of bile down the ducts
c. sphincterotomy, which means cutting of the sphincter or muscle that lies at the juncture of the intestine with both the bile and pancreatic ducts.)
What is a way to prevent gallstones?
UDCA (ursodeoxycholic acid) treatment
How does UDCA work?
efficacy of UDCA treatment has been debated and the mechanism of action in humans have still not been defined. UDCA, a bile acid with fewer hepatotoxic properties than endogenous bile acids, competes with the endogenous bile acids for absorption in the terminal ileum. Eventually, with therapy, ursodeoxycholic acid will become the predominant bile, accountin for up to 40% or 50% of the total bile-acid pool. It appears to promote the endogenous secretion of bile acid and to reduce the cytotoxic potential of endogenous bile acids, altering and reducing inflammatory cytokine production, protecting cell membranes from disruption, and reducing the display of abrrant HLA antigens.
(basically UDCA is also a bile acid but a healthier one. eventually, it becomes the main bile acid and doesn't do the damage endogenous bile acid would)
Where is VLDL created? What does it contain?
VLDL is created in the liver, containing "endogenous" TAGs and CE
Describe VLDL formation in the liver
Nascent VLDL enters the circulation containing Apo B-100 and amounts of Apo E and CII. As with chylomicrons,
additional Apo E and C‐II are donated to VLDL from HDL. The presence of Apo C-II stimulates LPL to degrade the
TAGs present in the particle, again resulting in the delivery of (liver-originating) fatty acids to adipose and
other peripheral organs. The result of action of LPL on the VLDL particle is its conversion to the VLDL-remnant (sometimes also called the IDL (intermediate density lipoprotein)).
What is the half-life of a VLDL particle?
The half‐life of a VLDL particle is expressed in terms of hours, not the fractions of hours that apply to chylomicrons.
Desribe processing of VLDL to LDL
Approximately half of the VLDL remnants are cleared from the circulation by the liver, via Apo E and its receptor (in a manner identical to that for chylomicrons). The remaining half are remodeled to LDL (low
remain in circulation. This
conversion requires the action of another lipase, hepatic lipase (HL), and the further elimination of both TAGs and PLs from the nascent LDL particle. As a consequence of the cumulative action of LPL and HL on these particles, the LDL particle is significantly enriched in CEs.
Describe the clearance of LDL (once VLDL)
(1) via the ldl receptor
(2) via scavenger receptor
What is the half-life of LDL ?
on the order of days
Describe clearance of LDL by the LDL receptor
Approximately two-‐thirds of the circulating LDL is taken up by the liver via Apo B-‐100 binding to the LDL receptor. The remaining third is taken up, for the most part via Apo B-‐100 and the LDL receptor, in peripheral tissues, thereby amounting to a significant source of cholesterol for
these peripheral tissues (along with endogenous synthesis). However, the LDL receptor is not the ONLY mechanism for clearance of LDL particles from the blood.
Describe clearance of LDL via the scavenger receptor?
Macrophages and some endothelial cell types posses a lower affinity but also broader specificity receptor, able to recognize both normal and "damaged" LDL particles
Turn over of red blood cells?
How is heme degraded?
By macrophage using heme oxygenase?
Function of heme oxygenase?
breaks one of the methynyl bridges holding the four part ring together, releasing green pigemented bilverdin, iron and carbon monoxide?
What is significant about the products in the reaction catalyzed by heme oxygenase?
this reaction is the only endogenous source of CO production. the products of heme oxygenase are shown to be cytoprotective. Bilverdin = antioxidant, CO = vasodilator (beneficial in stroke victims)
Purpose of biliverdin reductase
catalyze conversion of biliverdin to the red-orange colored bilirubin
Characteristics of bilirubin
poorly soluble in plasma (transported to the liver bound to albumin)
What happens to bilirubin in the liver?
In the liver, bilirubin glucuronyl transferase adds two molecules of glucuronic acid (itself a derivative of glucose) to bilirubin, making the more waer-soluble bilirubin diglucuronide
What is the fate of bilirubin digluuronide?
Secreted into the bile ducts and stored in the gall bladder until released into intestine
What does bacteria in the gut do to bilirubin?
Bacteria in the gut hydrolyzes conjugated bilirubin and reduce free bilirubin to a colorless, urobilinogen.
Fate of urobilinogen?
(1) oxidation to yield urobilins, which gives feces the characteristic brown color
(2) reabsorbed into the circulatory sysem, retrieved by the kidney, converted to urobilin (which gives urine its yellow color) and excreted in the urine
What is the function of haptoglobin?
a plasma glycoprotein that binds extracorpuscular hemoglobin in a tight noncovalent complex; the function of haptoglobin is to prevent loss of free hemoglobin into the kidney - conserves the valuable iron present in hemoglobin
Why are levels of haptoglobin low in patients with hemolytic anemia?
the half-life of Hb-Hp complex is about 90 minutes, the complex being rapidly removed from plasma by hepatocytes
Free hemoglobin and the glomerules
Free hemoglobin passes through the glomerulus of the kidney, enters the tubules, and tends to precipitate therein
What happens during van den Bergh reaction? What's its purpose?
Van den bergh reactions is still the most clinical hemistry laboratories to determine the seru bilirubin level. In this assy, bilirubin is exposed to diazotized sulfanilic acid, splitting into two relatively stable dipyrrylmethene azopigments that absorb maximally at 540 nm, allowing for photometric analysis. The direct fraction is that which reacts with diazotized sulfanilic acid in the absence of an accelerator substance such as alcohol. The direct fraction provides an approximate determination of the conjugated bilirubin in serum. The total serum bilirubin is the amount that reacts after the addition of alcohol. The indirect fraction is the difference between the total and the direct bilirubin and provides an estimate of the unconjugated bilirubin in serum.
(I really hope this doesn't matter, but basically take serum which has bilirubin in it expose it to a special acid. If you get emission of light after mixing bilirubin with special acid, that accounts for direct or conjugated bilirubin. find the total bilirubin concentration (didn't specify how) and substrate it by the now known conjugated/direct concentration)
What is Jaundice?
A condition characterized by yellow discoloration of the skin, conjunctivae, and mucous membranes as a result of widespread tissue deposition of the pigmented metabolite bilirubin.
Multiple causes/types of jaundice
(1) hemolytic jaundice
(2) obstructive jaundice
(3) obstructive jaundice
(4) hepatocellular jaundice
What happens during hemolytic jaundice?
Massive lysis of RBCs (caused by some other pre-existing condition) which releases heme in quantities that exceed the liver's capacity to process it to bilirubin diglucuronide. Bilirubin itself builds up in the blood and hence in peripheral tisues
What happens during obstrutive jaundice?
Obstructive jaundice stems from a mechanical obstruction of the bile duct (which in turn may have one of several causes), preventing the ‘draining’ of conjugated bilirubin into the intestines.
Color of feces resulting from obstructive jaundice?
Feces have a characteristic pale clay
color, due to the relative absence of the brown colored stercobilin
What happens during hepatocellular jaundice?
Hepatocellular jaundice occurs when damage to
liver cells (such as via liver disease, alcoholism, or hepatitis) results in a decrement in normal biochemical functions of these cells for heme metabolism, such that they cannot meet the loads presented even under otherwise normal circumstances. Both liver uptake of bilirubin and the conjugation of bilirubin can be affected.
What happen's during neonatal jaundice?
Neonatal Jaundice results, particularly in premature infants, due to low levels of the hepatic enzyme UDP-‐glucuronyl transferase (UDP-‐GT) at birth. Adult levels of UDP-‐GT is achieved in about a month.
How can neonatal jaundice be avoided?
To avoid the adverse neurologic outcomes of elevated circulating bilirubin levels, newborns receive phototherapy to improve the convert bilirubin to a more soluble derivative (which can be filtered in the urine).