Approach to Patients with Jaundice with Case

00:00 Welcome.

00:01 Today we'll talk about the general approach to the patient with jaundice.

00:06 So we'll start with a case.

00:08 An 85-year-old woman is admitted to the hospital with fever, epigastric pain and jaundice.

00:14 She has no known history of liver or biliary disease.

00:17 Her vitals are notable for temperature of 39.3C and heart rate of 110 bpm.

00:23 Physical exam reveals jaundice and right upper quadrant tenderness without rebound or guarding.

00:29 No hepatosplenomegaly is noted.

00:31 Her labs reveal a white cell count of 20,000/uL, ALT 420 (U/L) AST 360 (U/L) and total bilirubin 8.5 (mg/dL) with a direct bilirubin of 6.8 (mg/dL).

00:45 Right upper quadrant ultrasound reveals dilated intra and extrahepatic bile ducts with gallstones but no findings of cholecystitis.

00:54 So what is the most likely diagnosis? To help us answer that question, let's look at some key features.

01:00 So she has fever, epigastric pain and jaundice.

01:04 This should prompt you to remember Charcot's triad of cholangitis.

01:09 In addition, on her physical exam and her labs , we note that she meet sepsis criteria with fever, tachycardia and a high white count.

01:18 likely from a biliary source given her elevation in her liver test.

01:23 She has hyperbilirubinemia with a pattern of hepatocellular injury as well.

01:29 And on her ultrasound, we see common bile duct obstruction from the dilation of the bile ducts likely from a gallstone but we're not sure yet.

01:39 So now let's talk about the concept of jaundice.

01:43 Jaundice is a clinical sign when there is a disorder in bilirubin circulation typically only seen once serum bilirubin is above 2.5-3 (mg/dL).

01:53 There are three potential causes including: abnormal bilirubin metabolism, hepatocellular dysfunction and biliary obstruction.

02:04 So, there's a lot of terminology involved with discussing hyperbilirubinemia.

02:10 We'll have to first recall that bilirubin is conjugated in the liver for then excretion.

02:17 So labs may report a total bilirubin and they may also report a fractionated bilirubin as either direct or indirect bilirubin.

02:27 What do these terms mean? So, a direct bilirubin refers to conjugated bilirubin.

02:34 So that is bilirubin that has already been conjugated by the liver.

02:38 Whereas indirect bilirubin refers to unconjugated bilirubin so before it has reached the liver for conjugation.

02:48 It is helpful to think about jaundice in several large categories so we can think about it first in causes that occur before we get to the liver so prehepatic.

02:59 We may talk about causes within the liver, so intrahepatic.

03:03 And lastly posthepatic or after the liver.

03:07 So prehepatic causes tend to be from hemolysis or the breakdown of red blood cells.

03:14 Intrahepatic causes maybe from viral hepatitis, cirrhosis, or tumors or malignancies within the liver.

03:23 And posthepatic causes tend to be from gallstones or different types of cancer.

03:32 So in your initial approach to working up a patient with jaundice, these are some lab studies that you should make sure to get.

03:39 The first is your liver panel.

03:41 So this includes your AST, ALT, total and fractionated bilirubin, alkaline phosphatase, total protein and albumin.

03:50 Note that you may also want to get a GGT or gamma glutamylytanspeptidase.

03:56 This is a more specific test than alkaline phosphatase because it is more specific to the hepatobiliary system whereas alkaline phosphatase can be elevated from other conditions involving the bone.

04:09 You should also get a complete blood count or a CBC.

04:12 This is specifically to look for evidence of hemolysis by which you may see anemia.

04:19 You should also check your coagulation studies, again this is to look for potential signs of liver dysfunction.

04:26 And lastly, an abdominal ultrasound is helpful to look for any signs of obstruction.

04:32 So, there are many different ways to think about the diagnostic approach to hyperbilirubinemia.

04:38 This is one way that I think about it.

04:40 So when you're faced with high bilirubin, you can break it down into either an isolated elevation of the bilirubin or an elevation of a bilirubin along with an abnormal liver test.

04:53 When you have an isolated bilirubin elevation, you can break it down into whether it's unconjugated or mostly conjugated.

05:01 If it is mostly unconjugated, this is indirect bilirubin, your causes include hemolysis and other syndromes like Gilbert Syndrome and Crigler-Najjar.

05:13 If it is mostly conjugated which remember, is direct bilirubin then your causes are simply things like Dubin-Johnson or Rotor Syndrome.

05:23 On the other hand, if you also have abnormal liver chemistry test, then we can break it down into either a hepatocelllular pattern or a cholestatic pattern.

05:33 In the hepatocellular pattern, your causes are quite extensive but include viral hepatitis, drug-induced liver injury, autoimmune hepatitis and inherited conditions like Wilson's and alpha-1 antitrypsin and hemochromatosis.

05:48 On the other hand, and within the cholestatic pattern of elevation, you will have things like: gallstones, medications, PSC and PBC, cholangitis and various cancers or infiltrative diseases.

06:02 So now, let's go back to our prehepatic causes The mechanism by which people develop prehepatic jaundice is from metabolism of heme in the red blood cells.

06:14 So as red blood cells get destroyed by hemolysis, they then have breakdown of hemoglobin which then leads to production of bilirubin.

06:24 Remember again, this is unconjugated, indirect bilirubinemia because this is prior to transport to liver where the bilirubin will be conjugated and excreted.

06:37 So, there are many different types of hemolysis.

06:40 We can break them down in several large categories.

06:43 First you may have a defect in your red blood cell membrane as in G6PD deficiency or spherocytosis.

06:51 You may have a problem with the hemoglobin structure itself as in sickle cell disease or thalassemias.

06:58 And then there are other miscellaneous causes such as autoimmune hemolytic anemia or a large category of microangiopathic hemolytic anemias.

07:08 You may have resorption of a large hematoma or various medications can also induce hemolysisp Now let's move to our intrahepatic causes.

07:21 So these are... there are very many intrahepatic causes of cholestasis including viral hepatitis, infiltrative diseases, various cancers, medications, and genetic causes.

07:33 Know also that you may have cholestasis from sepsis itself or in states of pregnancy.

07:39 Now let's move to our posthepatic causes.

07:42 So, after the liver, causes of cholestasis include obstruction from gallstones, various infections or strictures of the biliary system.

07:52 You may have pancreatitis that leads to an obstruction and many different cancers can all impact to these area leading to an obstruction and thus, jaundice.

08:04 So now let's return to our case.

08:06 An 85-year-old woman is admitted for fever, epigastric pain and jaundice which is Charcot's triad of cholangitis.

08:13 She also meets sepsis criteria and her hyperbilirubinemia is mostly, now we know, a conjugated hyperbilirubinemia.

08:22 In addition, her ultrasound shows common bile duct obstruction and she has evidence of gallstones.

08:28 So putting this all together, we now know that she most likely has ascending cholangitis based on the Charcot's triad and recall that when you have a gallstone leading to obstruction, this is a posthepatic cause of jaundice.

08:42 So her most likely diagnosis is ascending cholangitis from a gallstone obstructing the common bile duct.