Jaundice Flashcards
What is jaundice?
Excess bilirubin accumulates and becomes visible as a yellow discolouration of the sclera, mucous membranes and/or skin dependent on skin pigmentation
Where does billirubin come from?
- Produced when the reticuloendothelial system breaks down red blood cells in a process known as haemolysis.
- Macrophages (reticuloendothelial cells) break down haemoglobin into haem and globin. Then, haem is further broken down into iron (which is recycled) and biliverdin by haem oxygenase. Biliverdin is then broken down further into bilirubin
What happens once bilirubin is produced in the body?
- Bilirubin is not water-soluble, so it relies on a transport protein (albumin) to be transported to the liver in the bloodstream.
- Once in the liver, glucuronic acid is added to the unconjugated bilirubin by glucuronyl transferase to form conjugated bilirubin, which is water soluble and can be excreted into the duodenum.
- Once the conjugated bilirubin reaches the colon, it is then deconjugated by colonic bacteria to form urobilinogen. The majority (80%) of urobilogen is oxidised by intestinal bacteria to create stercobilin, which is excreted via faeces and gives them their brown colour.
- The remaining 20% is reabsorbed into the bloodstream and transported to the liver, where some is used for bile production. The remainder is carried to the kidneys, oxidised into urobilin and excreted in urine (which gives urine its yellow colour).
What can the causes of jaundice be divided into?
Jaundice can be broadly divided into:
Pre-hepatic jaundice (unconjugated)
Intrahepatic jaundice (conjugated)
Post-hepatic jaundice (conjugated)
Pre-hepatic jaundice pathologies
Haemolytic anaemias
Gilbert’s syndrome
Crigler-Najjar syndrome
Intrahepatic jaundice pathologies
Viral hepatitis
Autoimmune hepatitis
Alcoholic hepatitis
Drug-induced hepatitis
Decompensated cirrhosis
Intrahepatic cholestasis
Extrahepatic jaundice pathologies
Common bile duct stone
Cholangitis
Bile duct strictures
Malignancy
Pancreatitis
What happens in pre-hepatic jaundice?
Pre-hepatic jaundice occurs when bilirubin metabolism has been affected before bilirubin reaches the liver (i.e., unconjugated bilirubin)
What happens in intrahepatic jaundice?
Occurs when hepatocyte damage results in reduced bilirubin conjugation or structural abnormalities that cause cholestasis.
What happens in extrahepatic jaundice?
Generally occurs when there is extrahepatic cholestasis, which often occurs due to distortion of the biliary tree due to intraluminal structural abnormalities (such as strictures) or extrinsic compression
Jaundice red flags
Red flags (urgent escalation):
- Haemodynamic instability or worried about a patient
- Decompensated disease (newly jaundiced, encephalopathic, ascites)
- Synthetic dysfunction – i.e. deranged clotting, bruising/petechiae/purpura/bleeding
- Septic
- Suspicion of paracetamol OD
- Significant abdominal tenderness
At what does jaundice become apparent?
The serum bilirubin level at which jaundice can be detected clinically is approximately 50 µmol/L
Most sensitive and specific imaging for bile duct stones
Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound scan (EUS) are the most sensitive and specific for the detection of bile duct stones, but MRCP is non-invasive
Abdominal ultrasound accuracy in detecting biliary system pathology
High sensitivity for diagnosing gallstones generally, but a reduced sensitivity for detecting common bile duct stones.
Accuracy of CT imaging for gallstones
- Around 20% of gallstones are not identified on CT imaging, and patients are exposed to unnecessary ionising radiation, so this is not the preferred choice of investigation.
- CT would be more appropriate if you suspected cholestasis secondary to malignancy
What do in patients with CBD stones
- National guidelines recommend that patients with common bile duct stones have a cholecystectomy in addition to bile duct clearance if there are no contraindications to surgery
- At most centres this is done in two stages: an ERCP followed by cholecystectomy on a subsequent admission.
- However, laparoscopic bile duct clearance can be done at the time of cholecystectomy which could be better for patients as it is a single procedure, reducing exposure to anaesthetic risks and avoiding the complications that can develop while waiting for definitive surgical treatment
Albumin as a marker of liver function
- Normal albumin level suggest preserved synthetic function. A
- Albumin has a half life as long as 20 days, so is not a reliable indicator of hepatic dysfunction in acute liver injury
Causes of acute liver injury
Transaminase levels in alcoholic hepatitis
- In alcoholic hepatitis, serum AST levels rarely rise above 500 iu/L and ALT rarely rises above 300 iu/L.
- In comparison, acute infectious hepatitis and drug and toxin injury often cause much higher ALT and AST rises.
The ratio of ALT to AST is also different in these two groups. Most causes of acute liver injury cause the ALT to rise more than the AST, however:
- In alcohol related disease, AST tends to rise higher than the ALT
- In alcoholic hepatitis and cirrhosis, the AST/ALT ratio is greater than 2 in around 70% of patients.
What is a non invasive liver screen?
A non-invasive liver screen generally refers to a series of non-invasive tests that help determine the cause of abnormal liver function tests
Hepatitis b markers and their significance
- Hepatitis B surface antigen (HBsAg)
A protein found on the surface of the hepatitis B virus that is raised in both acute and chronic infection, and indicates that an individual is infectious
This antigen is used in vaccination against hepatitis B - Hepatitis B surface antibody (anti-HBs)
This antibody is generated by the immune system in response to HBsAg
This usually represents development of immunity after vaccination or infection - Total hepatitis B core antibody (anti-HBc)
This antibody to core protein (found in the virion) appears at the start of acute symptoms and persists for life - IgM to hepatitis B core antigen (IgM anti-HBc)
This antibody indicates recent infection with hepatitis B within the last six months.
What suggests a patient has developed acute (fulminant) liver failure?
The presence of encephalopathy and coagulopathy show that he has developed acute (fulminant) liver failure
Fluid of choice in acute liver failure
Normal saline
What is the most important prognostic marker of acute liver failure?
The degree of coagulopathy and how it changes over time is the most important prognostic marker in acute liver failure
PT vs apTT bleeding risk
Prothrombin time reflects the activity of only a small number of clotting factors and does not reflect bleeding tendency
What is acute liver failure?
A liver injury in combination with a disorder of coagulation and encephalopathy, in a patient without known liver disease where the duration of illness is less than 26 weeks (if later than it is chronic)
Most common cause of acute liver injury?
The most common cause in the UK is paracetamol induced liver injury
Examination findings suggestive of chronic liver disease
Examination findings that suggest an individual may have chronic liver disease include spider naevi, clubbing, palmar erythema, caput medusae, and gynaecomastia
Investigation results that suggest chronic liver disease
Investigation results that suggest chronic liver disease are:
- Low albumin and prolonged clotting times, reflecting impaired protein synthesis
- Low platelets, reduced thrombopoeitin synthesis, and peripheral platelet consumption
Why are low platelets seen in chronic liver disease?
Caused by splenic platelet sequestration secondary to portal hypertension
Prescribing Paracetamol in patients with liver damage
Evidence shows that a reduced dose of paracetamol in cirrhotic patients, even with decompensated disease, is safe, and should be used as first line analgesia as it has few other side effects. [47] Up to 4 g per day is well tolerated by most cirrhotic patients in the short term. [48] Low body weight (below 50 kg) and risk factors for glutathione deficiency, eg malnutrition and chronic alcohol ingestion, increase the risk of harm, so reduction in dose may be appropriate
Prescribing NSAIDs in patients with liver damage
- NSAIDs should be completely avoided because of the risk of causing decompensation through gastrointestinal bleeding or renal dysfunction
- Gastrointestinal bleeding is a particular concern in cirrhotic patients because they may have portal hypertensive gastropathy, varices, and coagulation abnormalities.
Prescribing opiates in patients with liver damage
- Opioid analgesics should be used with caution or avoided where possible, as they carry a risk of causing hepatic encephalopathy and their metabolism can be altered.
- Doses should be reduced, patients carefully monitored, and laxatives prescribed preemptively to reduce the risk of constipation.
- Codeine is best avoided because it has a reduced analgesic effect in cirrhosis (it requires first pass metabolism in the liver to be activated), but it can still accumulate and cause adverse effects.
Why are ascitic taps dones?
It is key to excluding spontaneous bacterial peritonitis, which has a prevalence of around 15% in hospitalised patients with decompensated liver disease
Spontaneous bacterial peritonitis symptoms
Spontaneous bacterial peritonitis can cause abdominal pain, fever, and altered gastrointestinal motility and decompensation of liver disease, or it can be asymptomatic
Where to take ascitic tap?
3cm superior and then 3cm medially to the anterior superior iliac spine
