Sample Lesson – Gilbert Syndrome + LFTs (AST/ALT/ALP), Conjugated Vs. Unconjugated Bilirubin, Acute Vs. Chronic Liver Failure, And The Color Of Blood/Pee/Poop/Pus



Next Step: Make Cards on the Automatic Key Concepts, and Vignettes

Remember, the more you automatically know what each sentence means on your test, the better you will do. There are 4 stages in making interpretation more automatic:

  • Stage 1: Unable to Make Pathophysiologic Chronologies in Either Timed or Untimed setting
  • Stage 2: Basic Pathophysiologic Chronologies, but with Significant Gaps
  • Stage 3: Detailed Pathophysiologic Chronology Without Time, but Unable to Consistently Generate PC During Timed Setting
  • Stage 4: Consistent Pathophysiologic Chronologies in Timed Setting

My goal with these vignettes is to help you reach Stage 4. How do you do so?

  • With the Automatic Key Concept cards, you can master the underlying information to move past Stages 1 + 2.
  • Then, with the Vignette/Pathophysiologic Chronology cards, you can teach yourself to make these connections on your exam.

summary of key concepts:



Automatic Key Concepts:

Copy + paste these into your cards, to make these key concepts more automatic.


What organ does most of the bilirubin in your blood come from? Why does that make sense?

Spleen – this where blood is broken down (where you “retire” the old RBCs)

Bilirubin is a breakdown product of heme


What color is O2-bound heme? Why?

Red – porphyrin rings absorb light in the visible spectrum, as do many compounds with conjugated double-bonds

Fun fact – chlorophyll, which gives plants their green color, also is a porphyrin ring


What color is bilirubin? Why?

Yellow – bilirubin is the breakdown product of heme, which is based on a porphyrin ring structure. Both have many conjugated double-bonds, and absorb light in the visible spectrum


What color is poop? Why?

Bacterial breakdown: bilirubin → urobilinogen → stercobilin → poop brown


What color is pee? Why?

Bilirubin broken down by bacteria → urobilinogen → reabsorbed into bloodstream → filtered in urine → air oxidation → urobilin → pee yellow


What important immune system enzyme uses a porphyrin ring? What color is it?

Myeloperoxidase – used in the neutrophil “respiratory burst” – contains heme → green color


Pneumonia – what question can you ask to help differentiate between bacterial and viral pneumonia? Why?

If there is sputum, what color is it? If green/yellow – indicates neutrophil presence, since their myeloperoxidase is green. Presumably if the heme breaks down (i.e., there are more dead neutrophils) → yellow color of bilirubin


If you suspect physical abuse rather than someone who “fell down the stairs” what physical evidence can help confirm your suspicions?

Look at the age of the bruises. Bruises that happened at the same time would all have the same color (e.g., they’d all be red with fresh blood leaking into the tissue)

Bruises where the heme has broken down → yellow

If the age of the bruises don’t match (i.e. some are red and some are red-yellow) → could not have occurred during the same incident

Also: defensive injuries (e.g., forearm bruising from using arms to block an attack)


Is (unconjugated) bilirubin water soluble or not? Why?

NOT water soluble – bilirubin = breakdown product of heme, which is based on a nonpolar porphyrin ring. It would make sense that the breakdown product of something nonpolar (heme) would itself be nonpolar (bilirubin)


Unconjugated bilirubin – will this be absorbed by the GI tract? Why/why not?

Unconjugated bilirubin is absorbed readily by GI tract. Recall that unconjugated bilirubin is a breakdown product of heme. Both heme (which uses a nonpolar porphyrin ring) and unconjugated bilirubin are non-polar → cross cell membranes easily → absorbed in GI tract easily.


What does “conjugation” of bilirubin accomplish?

Conjugate something to bilirubin to make it polar / water-soluble, so that it stays within the lumen of your GI tract and doesn’t cross the membranes into the bloodstream


Direct bilirubin – what does it refer to?

It refers to the conjugated bilirubin

FYI: Technically, they add a diazo reagent, which reacts more readily with the hydrophilic fraction of the bilirubin. Since the conjugated bilirubin is what you ”directly” measure → “direct bilirubin” (they then add something to accelerate the reaction in the hydrophobic fraction to measure the total bilirubin)


Indirect bilirubin – use what it is to explain how you would calculate it

It is the unconjugated bilirubin. It isn’t directly measured (hence the name “indirect”) – you can calculate it by:

Indirect bilirubin = total – direct bilirubin


Primary biliary cholangitis vs. primary sclerosing cholangitis – what is the difference?

PBC: Destructive disorder of the intrahepatic biliary tree.

PSC: Involves both the extrahepatic and intrahepatic biliary tree.


Unconjugated bilirubin – use whether it is water soluble or not to explain whether an unconjugated hyperbilirubinemia would lead to dark urine

Would NOT lead to dark urine

Unconjugated bilirubin = poorly water soluble → stays bound to albumin → will not be filtered via kidneys to urine → urine not dark


Conjugated hyperbilirubinemia – would this lead to dark urine or not? Why?

WOULD lead to dark urine

Bilirubin conjugation → water-soluble → stays dissolved in serum → filtered via kidneys to urine → dark urine


If you had complete blockage of the common bile duct, what color would the stool be? Why?

”Clay-colored” – bilirubin would NOT be able to enter the GI tract → breakdown into urobilinogen ↓↓ → formation of stercobilin ↓↓ → no brown color in stool


If you had complete blockage of the common bile duct, what color would the urine be? Why?

Dark urine – conjugated bilirubin wouldn’t enter the GI tract, but would back-up into liver/bloodstream → conjugated hyperbilirubinemia → soluble in serum (because it’s conjugated) → filtration through the kidneys → enter urine → dark urine


Gilbert syndrome – use the genetic basis to explain what you would see on liver function tests

UDP-glucuronyltransferase activity ↓ → ability to conjugated bilirubin ↓ → isolated (unconjugated) hyperbilirubinemia


Aspartate aminotransferase (AST), alanine aminotransferase (ALT) – if these are elevated on serum tests, what does this indicate?

These enzymes are found INSIDE of cells. They are not specific to liver cells, but are found in high concentrations inside of liver cells. If they are elevated in the serum, then it is an indication of liver damage.


Alkaline phosphatase – what organs release the majority of it?

80+% is released from liver and bone, and in small amounts from the intestine; also released from placenta (isolated ALP increase in pregnant women)


Alkaline phosphatase – use its proposed role in bone to explain what bone conditions it is elevated

Found in osteoblastic (bone-forming) diseases, like Paget’s, vitamin D deficiency, or even children (presumably due to their increased bone formation)

Interestingly, it is NOT known what the general function of alkaline phosphatases are in most cases


Alkaline phosphatase – elevated levels indicate what in the liver? How is this thought to occur?

Biliary obstruction → ALP ↑

Interestingly, rather than simply being that ALP “spills” into the blood from the biliary tract, ALP synthesis actually increases in biliary obstruction.


Alkaline phosphatase – if you see an elevation, what test should you order next? Why?

GGTP (gamma-glutamyl transferase), which is more specifically found in biliary obstruction, rather than elevation for other things (e.g., bone formation, placenta, etc.)


LFTs – use what is measured to explain why it is a misnomer

This is a misnomer, because it is not really a measure of liver function


What is measured instead, to measure synthetic liver function? Why?

Serum albumin, and prothrombin time (PT)

Albumin is made in the liver

Most coagulation factors are also made in the liver; liver synthetic function ↓ → coagulation factors ↓ → PT ↑


In liver failure, what is affected first, the serum albumin levels or the PT? Why?

PT is affected first. Factor VII has a short half-life (3-6 hours), and thus must be made constantly. If synthesis stops → factor VII levels ↓ quickly → PT ↑

Albumin has a half-life of weeks (18-20 days). If the liver stopped making albumin → levels wouldn’t fall for weeks


Acute vs. chronic liver failure – what lab values would you measure to differentiate? How can you use the results to differentiate between the two?

Measure serum albumin and PT (prothrombin time)

Acute liver failure: serum albumin normal, PT ↑ (if synthetic liver function stopped for hours/days, factor VII levels fall rapidly, but serum albumin – which has a half-life of 18-20 days – wouldn’t fall for weeks)

Chronic liver failure: serum albumin ↓, PT ↑ (if synthetic liver function stopped for weeks, factor VII levels would have already fallen, but serum albumin would also be low)

vignette/pathophysiologic chronologies:


A 15-year-old boy comes to his physician for nausea and vomiting for the past 2 days after a school potluck. Several of his classmates and teachers reported similar nausea and vomiting. Temperature is 37 C (98.6 F), blood pressure is 120/80 mmHg, and pulse is 72/min. On exam, there is mild scleral icterus. Abdomen is soft, non-tender, and mildly distended. Labs are significant for:

What is the pathophysiologic chronology?



Gilbert: Born with UDP-glucuronyltransferase (UGT1A1) activity ↓ → asymptomatic, until has GI illness → conjugation of bilirubin ↓ → isolated unconjugated hyperbilirubinemia


Born with UDP-glucuronyltransferase (UGT1A1) activity ↓ → asymptomatic, until has GI illness → nausea/vomiting/anorexia + illness → UDP-glucuronyltransferase ↓ further → conjugation of bilirubin ↓ → isolated unconjugated hyperbilirubinemia → bilirubin poorly water soluble → bilirubin stays bound to albumin → NOT filtered via nephron → urine not darker (unlike conjugated hyperbilirubinemia which has darker urine)


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