Session 7 - Lecture 1 - Jaundice Flashcards
1 - Title
Jaundice and LFTs
“Think about this as like a part 2 to the lecture we did last week thinking about liver disease and gall bladder pathologies”
2 - Intended Learning Outcomes
Intended Learning Outcomes
To define jaundice
To explain how jaundice relates to haem/bilirubin metabolism
To describe the clinical presentation of jaundice
To identify common pathology that can cause jaundice:
◦ Pre-haptic
◦ Hepatic
◦ Post-haptic
To recognise malignancy of the pancreas as an important cause of jaundice
To state what tests are included in Liver Function Tests (LFTs)
To be able to interpret abnormal LFTs in the context of jaundice
“So these are some of our LOs, again, should be in your book or on Bb, think about what jaundice actually is – know it’s a clinical sign but what is it telling us – how it relates to bilirubin metabolism, clin presentation goes hand in hand but really think about what we learnt last week of diff pathologies, and how diff pathologies can cause diff reasons for causing jaundice – some specific important pathologies, and link that together with LFTs and give you a basis of how to think and interpret LFTs in context of disease processes.”
3 - What is jaundice?
Jaundice
Clinical manifestation of raised bilirubin
“clinical manifestation of hyperbilirubinaemia (raised bilirubin levels in the blood)”
4 - Clinical features of jaundice
Clinical features of jaundice
‘Jaune’ = yellow
Look for other signs of liver disease
https://www.nhs.uk/conditions/jaundice/
“think that jaune is Francais means yellow, so jaundice is essentially the yellow discoloration, bc of the kind of pigmented nature it turns up in the eyes – sclera of eyes can be white, and can make skin look yellow as well – sometimes q hard to detect skin changing colours – quite helpful to think, put someone else’s hand or own hand if you yourself have pale skin, put it next to each other, compare the two, look – always think about this as well in terms of abdo examination, looking for other signs of liver disease – is it bc of liver and how can you detect that – is there enlarged liver, hepatomegaly; portal hypertension, ascites, varices; splenomegaly (Splenic vein drains into portal vein – backlog can cause engorgement, enlargement of the spleen) other signs to think about in CHDD on abdominal examination, so important point if you see someone jaundiced – other markers/signs giving you a hint of what’s going on.”
5 - Bilirubin
Bilirubin
Breakdown product of haem
◦ Unconjugated state bound to albumin
Conjugated in the liver
◦ Water soluble
Excreted in urine and faeces
It’s important to understand bilirubin metabolism to be able to identify where in the process things might go wrong…
ERYTHROCYTES Haemoglobin --> Splenic macrophages (engulf and digest erythrocytes) SPLEEN Haemoglobin --> Haem --> Globin --> Bilirubin (unconjugated/protein bound) --> BLOOD LIVER Conjugation --> Bilirubin (conjugated/water-soluble) --> GUT Urobilinogen --> FAECES
Bilirubin (conjugated/water-soluble)
–> KIDNEY Urobilinogen
Urine –> Urobilinogen
ENTEROHEPATIC CIRCULATION
BILE –> Urobilinogen
GUT or KIDNEY
https://www.liverpool.ac.uk/~trh/local_html/jaundice/flow_diagram_of_bilirubin_metabo.htm
6 - Causes of Jaundice
Causes of Jaundice
PRE-HEPATIC: Too much haem
HEPATIC: Reduced hepatocyte function
POST-HEPATIC: Obstructive causes
[Colour-coded diagram Yellow Orange liver Red drainage Green gall bladder]
“So causes of jaundice, green gall bladder just for completion, bc we can’t talk about liver without talking about BFF gall bladder.
Pre-hepatic (yellow) – before the liver; mainly problems before things enter liver
Hepatic (orange) – cause in liver; process of bilirubin metabolism it’s doing
Post-hepatic (red) – draining or processing of bilirubin; anything that will obstruct way of bile getting into rest of GI tract will cause post-hepatic jaundice”
7 - PRE-HEPATIC
PRE-HEPATIC Too much haem Caused by INCREASED DEGRADATION of haemoglobin ◦ Liver conjugating ability is fine ◦ Excretion pathway is fine Too much demand on the liver
Therefore, the levels of bilirubin that are raised tend to be UNCONJUGATED
“So pre-hepatic jaundice: too much haem, okay, so if we think about the metabolism of bilirubin itself, let me just flick back, bc I think I have a slide sorry I thought I had a slide here but it’s coming later, but essentially this is to do with increased degradation of Hb, Hb metabolism – haem is splitfrom globin (processed to form AAs and other recycled things) but haem metabolised by spleen by reticulocyte system to form bilirubin. So anything here, causing too much ahem to build up is essentially overloading the liver’s ability to conjugate bilirubin, pre-hepatic jaundice, excretion pathway is fine, not a problem here, it’s a problem building up, too much haem – can’t process bc too much demand on it – increased lvls of bilirubin in blood, can diff that into unconjugated so not water soluble (bound to proteins) or conjugated – water soluble, freely travel through GI tract and blood as well. Pre-hepatic jaundice, too much haem, liver can’t conjugate it all, so levels of raisedbilirubin levels tend to be unconjugated.”
8 - Common Causes of Pre-Hepatic Jaundice
Common Causes of Pre-Hepatic Jaundice Haemoglobinopathies ◦ Sickle cell ◦ Thalassaemia ◦ Spherocytosis Damage to red blood cells ◦ Haemolysis
[neonatal jaundice]
“So common causes of pre-hepatic jaundice so basically anything that will cause increased breakdown of RBCs – haemoglobinopathy – metabolism, haemoglobin – anything that makes a RBC kmore likely to breakdown will lead to increased levels of haem and bilirubin, can have other causes ofh aemoloysis as well, autoimmune reactions such as Rhesus disease of the newborn, or infections like malaria, that target RBCs, so that could be another reason why you’re getting destruction and haemoloysis of RBCs – cute lil picture up kjist as a reminder that newborn babies can develop jaundice – link to repro, bc their liver is often immature so it kind of struggles to do that conjugating, so normal physiologically, first day or so of life, need treatment relating to jaundice, other thing we’ll say, unconjugated bilirubin, it can cross the BBB and cause significant alterations in terms of development and function, so worry about that in newborns – will learn about it in paediatrics.”
9 - HEPATIC
HEPATIC Reduced hepatocyte function
This is caused by REDUCED CONJUGATING ability of the liver
◦ Damage to hepatocytes
◦ Amount of bilirubin is fine
◦ Excretion pathway is /usually/ fine
Therefore, you get a MIXED PICTURE of CONJUGATED AND UNCONJUGATED BILIRUBIN
[liver picture]
“So hepatic, so this is reduced hapeoticyte function, essentially the liver bc you have damage to hepatocytes it can’t conjugate as ewfdfectively bc it has less effective hepatocytes that are doing the conjugating. So amount of bilirubin going in is fine, excretion npathway is usually fine although in some kind of liver disease can get obstruction of the intrahepatic ducts but normally fine, so you can get a mixed picture of conjugated and unconjugated – due to a mixture of ability in the liver, some can but some are damaged, with hepatic diseases, can get pressure on duct system, but that’s more of a finer point rly, for simplicity, easier to separate the 2 and think of them as hepatic and obstructive causes.”
10 - Common Causes of Hepatic Jaundice
Think back to last week’s lecture…
Common Causes of Hepatic Jaundice
Think back to last week’s lecture…
Cirrhosis
- Alcoholic Liver Disease
- Viral Hepatitis
- Medication
- Autoimmune Hepatitis
- Hereditary Haemochromatosis
- Wilson’s Disease
“Think about some of the causes we talked about that can cause damage to liver hepaotcytes that might give you hepatic jaundice. So last week we talked a lot about conditions that can affect the liver particularly chronic conditions
Cirrhosis – hallmark feature is hepatocyte necrosis – so essentially that’s at the centre of long-term conditions that can lead to jaundice,
Viral - Hepatitis C or B (viral hepatitis)
Medications - Some long term medications are hepatotoxic e.g. methotrexate, although acute ones that can cause hepatocyte damage acutely
Autoimmune - certain antibodies associated with this condition, but it’s basically autoimmune destruction of the hepatocytes themselves
Storage disorders (HH & WD)
Also important to remember that it’s not just chronic conditions that can cause jaundice, so we do have some examples of acute things that can cause damage.
Acute cholangitis – we’ll come to that later on in the lecture bc it won’t cause hepatic jaundice necessarily but linked”
11 - Common Causes of Hepatic Jaundice (Acute)
Common Causes of Hepatic Jaundice Also bear in mind that jaundice can occur in acute liver damage ◦ Paracetamol toxicity ◦ Viral hepatitis ◦ Other infections
“Such as we know paracetamol toxicity – big one, link back to metabolism – breakdown of paracetamol can cause significant liver damage – chronic ones of Hep B and C but Hep A and D and E are more acute – other more acute infections that can cause it, and other kind of weird and wonderful infections as well such as leptospirosis, if you’ve covered it in infection then cool, if not dw, in short term can lead to destruction of hepatocytes, therefore hepatic jaundice.”
12 - POST-HEPATIC
POST-HEPATIC Obstructive causes
This is caused by OBSTRUCTION to the excretion pathway
◦ Amount of bilirubin is fine
◦ Conjugating ability of the liver is fine
Therefore, the raised bilirubin tends to be CONJUGATED
“So post-hepatic jaundice, the final kind of part of our categories, in post-hepatic, this is obstruction to the excretion pathway, will show you a pic of excretion pathway by way of biliary tree, but thinking amount that’s coming in is absolutely fine, ability of liver to conjugate it is absolutely fine, there’s some sort of problem here that is obstructing its normal metabolism, so it’s obstructing its ability for the bilirubin to enter the GI tract, therefore goes down other pathways, and I’ll show you what I mean by that, in this condition, levels of increased bilirubin tends to be conjugated bc conjugating ability of the liver is fine i.e. water soluble, sometimes you just get a total bilirubin level in LFTs, sometimes won’t be broken down to you in conjugated and unconjugated, and again, more kind of tools you can have to figure out where it’s coming from, tell you something about the functionality of the liver and where the excess is coming from.”
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