Hepato-biliary: Jaundice and Liver function assessment Flashcards
(85 cards)
1
Q
What is the definintion of jaundice?
A
Yellowing of the skin, sclerae, and other tissues caused by excess circulating
2
Q
At what bilirubin level does jaundice become clinically evident?
A
Serum levels exceed 51 micromol/L (3 mg/dL).
First shows in sclera because of high affinity for bilirubin
3
Q
How are red blood cells broken down?
A
Macrophages breakdown haem into bilirubin
4
Q
What is bilirubin conjugated with?
A
Glucouronic acid (water soluble)
5
Q
What transports unconjugated bilirubin in the blood?
A
Albumin
6
Q
Where is bilirubin secreted into after it has been conjugated with glucuronic acid?
A
Into bile and then the intestine
7
Q
What happens to conjugated bilirubin when it enters the bowel?
A
Glucuronic acid is removed by intestinal bacteria
8
Q
What happens to bilirubin once the glucuronic acid has been removed by bacteria?
A
Converted to urobilinogen
9
Q
What happens to urobilinogen in the intestine?
A
- Absorbed from the gut -> to kidney
- Oxidised to stercobilinogen -> faeces
10
Q
What is urobilinogen converted to in the kidneys?
A
Urobilin - characteristic colour of urine
11
Q
Bilirubin is excreted as:
A
Urobilinogen (from kidney - 13%)
Urobin (from stool - 99%)
That which is not excreted is put back into the enterohepatic circulation
12
Q
Describe the pathway of billirubin (the whole sha-bang)
A
Pre-hepatic
Spleen:
- Haemoglobin breaks down into haem + globin
- Haem converted into bilirubin
- Bilirubin bound to albumin to make Bilirubin-Albumin Complex (+ travels in blood to liver)
- Unconjugated bilirubin (water insoluble so can’t appear in urine due to HMW plasma protein)
Hepatic
Liver:
- Uptake of bilirubin by hepatocytes
- Conjugation of bilirubin in hepatocytes (becomes water soluble) so can appear in urine/stool
- Excretion of conjugated bilirubin into biliary system
Post-hepatic
3 routes for bilirubin:
- Transport of conjugated bilirubin in biliary system- excreted as
- Uroblinogen
- Uroblin
- Breakdown of conjugated bilirubin in intestine
- Further metabolised into stercoblin (gives stool brown colour)
- Reabsorption of bilirubin into entero-hepatic circulation
13
Q
What are causes of unconjugated hyperbilirubinaemia?
A
- Overproduction - Haemolysis, ineffective erythropoesis
- Impaired hepatic uptake - Drugs, ischaemic hepatitis
- Impaired conjugation - Gilbert’s syndrome, Crigler-Najjar
- Physiological neontala jaundice
14
Q
What sort of hyperbilirubinaemia occurs in pre-hepatic jaundice?
A
Unconjugated hyperbilirubinaemia
15
Q
What type of hyperbilirubinaemia occurs in gilbert’s syndrome?
A
Unconjugated hyperbilirubinaemia
16
Q
What types of jaundice cause conjugated hyper bilirubinaemia?
A
- Hepatocellular dysfunction
- Post-hepatic/Cholestatic jaundice
17
Q
What are causes of hepatocellular jaundice?
A
- Viral hepatitis
- CMV
- EBV
- Drugs
- Alcohol/Cirrhosis
- Liver mets
- Liver abscess
- Haemochromatosis
- Autoimmune hepatitis
- Septicaemia
- Leptospirosis
- Syphilis
- Alpha1-antitrypsin
- Budd chiari
- Wilson’s Disease
- Right heart failure
- Toxins
18
Q
What are causes of post-hepatic jaundice?
A
- PBC, PSC
- Drugs
- CBD gallstones
- Pancreatic cancer
- Compression of the bile duct
- Cholangiocarcinoma
- Choledochal cyst
- Mirrizi’s syndrome
- Caroli’s syndrome
19
Q
Presentation of pre-hepatic jaundice
A
Normal urine
Normal stool
20
Q
Presentation of hepatic jaundice
A
Dark urine
Normal/pale stool
21
Q
Presentation of post hepatic jaundice
A
Dark urine
Pale stool
22
Q
Causes of pre-hepatic jaundice
A
- Haemolysis
- Haemolytic anaemia eg spherocytosis
- Post transfusion
- Gilbert’s syndrome (harmless, no treamtent needed)
23
Q
Causes of hepatic jaundice
A
-
Increase in unconjugated (liver function)
- Hepatitis
- Liver failure
- Drugs
-
Increase in conjugated (swelling of hepatocytes)
- PBC - granumomatous inflammation inolving bile ducts (progression to hepatic cirrhosis)
- PBS - chronic inflammation involving bild ducts (progression to hepatic cirrhosis, increased risk cholangiocarcinoma)
- Cirrhosis - liver failure, PHT, HCC. Alcohol, hepB and C, immune mediated liver disease, metabolic disorders
- Liver/hepatocellular carcinoma - malignant tumour of hepatocytes
- Metastases
- Pregnancy
24
Q
Causes of post hepatic jaundice
A
-
Common bile duct obstruction
- CBD stones
- Strictures (benign/malignt)
- External compression tumours - head of pancreas
- Pancreatitis
-
Cholelithiasis/gall stones
- Acute
- Chronic
- Miritzzi syndrome - gallstones that compress CBD
25
Features of pre-hepatic jaundice in history
Anaemia: fatigue, SOB, pallor, chest pain
26
Features of hepatic jaundice in history
Risk factors for liver disease:
IVDU
Alcohol
Drug history
27
Features of post-hepatic jaundice in history
* **Calcular**
* **Biliary colic**
* **Fluctuating jaundice**
* **No weight loss**
* **Malignant**
* **Constant abdo pain**
* **Progressive jaundice**
* **Weight loss**
* **Cholesostasis**
* **Pruritis**
* **Dark urin**
* **Pale stool**
28
Features of pre-hepatic jaundice on examination
Anaemia: pallor
Splenomegaly
29
Features of hepatic jaundice on examination
Signs of chronic liver disease
General - asterixis, fetor hepaticus
Abdo inspectiono - spider naevia, gynaecomastia
Abdo palp - Ascites, hepatomegaly
30
Features of post-hepatic jaundice on examination
General: jaundice, fever, weight loss
Abdo palpation: hepatomegaly
Courvosier's sign
31
Blood tests pre-hepatic jaundice
Bilirubin - increased unconjugated
AST/ALT normal
ALP normal
32
Blood tests hepatic jaundice
Billirubin - increased both
AST/ALT: marked increase (++++)
ALP: increase/normal
33
Blood tests post hepatic jaundice
Billirubin - increased conjugated
AST/ALT - mild increase/normal
34
What blood tests are used to assess liver function?
* **Alanine transaminase (ALT)**
* **Aspartate aminotransferase (AST)**
* **Alkaline phosphatase (ALP)**
* **Gamma-Glutamyltransferase (GGT)**
* **Bilirubin**
* **Albumin**
* **Prothrombin time (PT)**
35
What tests are used to distinguish between hepatic and post-hepatic jaundice?
* **ALT**
* **AST**
* **ALP**
* **GGT**
36
What tests are used to assess livers synthetic function?
* **Bilirubin**
* **Albumin**
* **PT**
37
What is ALT a useful marker of?
**Hepatocellular injury** - found in high concentrations in hepatocytes and enters blood following hepatocellular injury
ALT more specific to the liver - normal levels 5-40u/l
AST also present in heart and skeletal muscle - normal level 10-40u/l
38
What is ALP a useful marker of?
**Cholestasis** (**Indirect marker** ) - particularly concentrated in the liver, bile duct and bone tissues. It is raised in liver pathology due to increased synthesis in response to cholestasis
39
What can also cause a raised AlkP
Pregnancy
Paget's
Osteomalacia
Growting children and bone mets
40
What LFT results would indicate predominantly hepatocellular injury?
* **ALT** - \> 10-fold increase
* **ALP** - \<3-fold increase
41
What LFT results would indicate cholestasis?
* **ALT -** \<10-fold increase
* **ALP** - \>3-fold increase
* **Raised GGT**
42
What are causes of an isolated rise in ALP?
* **Bony metastases / primary bone tumours (e.g. sarcoma)**
* **Vitamin D deficiency**
* **Recent bone fractures**
* **Renal osteodystrophy**
* **Paget's Disease**
43
How would you distinguish between hepatocellular jaundice and cholestatic jaundice?
Compare to what degree the ALT and ALP are raised. If ALT is raised markedly compared to the ALP, this is primarily a hepatocellular pattern of injury. If ALP is raised markedly compared to ALT, this is primarily a cholestatic pattern of injury.
44
What is a raised GGT indicative of?
Can be suggestive of biliary epithelial damage and bile flow obstruction.
It can also be raised in response to alcohol and drugs such as phenytoin.
A markedly raised ALP with a raised GGT is highly suggestive of cholestasis.
45
What would a raised ALP in the absence of raised GGT suggest?
**Non-hepatobiliary cause** - Alkaline phosphatase is also present in bone and therefore anything that leads to increased bone breakdown can elevate ALP.
46
What would jaundice with normal ALT/ALP levels suggest?
**Pre-hepatic cause** - Gilbert's syndrome, haemolysis
47
What are the livers main synthetic functions?
* **Conjugation and elimination of bilirubin**
* **Synthesis of albumin**
* **Synthesis of clotting factors**
* **Gluconeogenesis**
48
What investigations can be used to test liver synthetic function?
* **Serum bilirubin**
* **Serum albumin**
* **Prothrombin time (PT)** - Absence of bile, failure of fat soluble vit K absorption (vit K needed for clotting factor synthesis
* **Serum blood glucose**
49
What happens to an individuals stool and urine if they have unconjugated hyperbilirubinaemia?
Normal urine and normal stool
50
What would the colour of someones stool be if they had hepatic jaundice?
Dark urine, normal stool
51
What colour is the stool and urine in someone with post-hepatic jaundice?
Pale stool, dark urine
52
What can cause albumin to fall?
* **Liver disease resulting in a decreased production of albumin (e.g. cirrhosis)**
* **Inflammation triggering an acute phase response which temporarily decreases the liver’s production of albumin**
* **Excessive loss of albumin due to protein-losing enteropathies or nephrotic syndrome**
53
What is PT, and what can it indicate in terms of liver disease?
Prothrombin time (PT) is a measure of the blood’s coagulation tendency, specifically assessing the extrinsic pathway.
In the absence of other secondary causes such as anticoagulant drug use and vitamin K deficiency, an increased PT can indicate liver disease and dysfunction.
54
What does an ALT \> AST tend to indicate when looking as the ALT/AST ratio?
Chronic liver disease
55
What does an AST\>ALT tend to indicate when looking as the ALT/AST ratio?
* **Cirrhosis**
* **Acute alcoholic hepatitis**
56
What LFT profile might be present in someone with acute hepatocellular damage?
* **Markedly increased ALT**
* **Normal/increased ALP**
* **Normal/increased GGT**
* **Increased/Markedly increased Bilirubin**
57
What LFT profile might you see in someone with Chronic hepatoceullular damage?
Normal or increase ALT, ALP, GGT and Bilirubin
58
What LFT profile might you see in someone with Cholestasis?
* **Normal/increased ALT**
* **Mardkedly increased ALP**
* **Markedly Increased GGT**
* **Markedly increased Bilirubin**
59
What are common causes of acute hepatoceullular damage?
* **Poisoning (paracetamol overdose)**
* **Infection (Hepatitis A and B)**
* **Liver ischaemia**
60
What are common causes of chronic hepatocellular injury?
* **Alcoholic fatty liver disease**
* **Non-alcoholic fatty liver disease**
* **Chronic infection (Hepatitis B or C)**
* **Primary biliary cirrhosis**
61
What are rare causes of chronic heptocellular injury?
* **alpha-1 antitrypsin deficiency**
* **Wilson’s disease**
* **Haemochromatosis**
62
What tests are included in a liver screen?
* **LFTs**
* **Coagulation screen**
* **Hepatitis serology (A/B/C)**
* **Epstein-Barr Virus (EBV)**
* **Cytomegalovirus (CMV)**
* **Anti-mitochondrial antibody (AMA)**
* **Anti-smooth muscle antibody (ASMA)**
* **Anti-liver/kidney microsomal antibodies (Anti-LKM)**
* **Anti-nuclear antibody (ANA)**
* **p-ANCA**
* **Immunoglobulins** – IgM/IgG
* **Alpha-1 Antitrypsin** – Alpha-1 Antitrypsin deficiency
* **Serum Copper** – Wilson’s disease
* **Ceruloplasmin** – Wilson’s disease
* **Ferritin** – Haemochromatosis
63
If someone presented with jaundice, what would you want to ask them in the histroy?
Ask about
* **Blood transfusions**
* **IV drug use**
* **Body piercings/Tattoos**
* **Sexual activity**
* **Travel abroad**
* **Family history**
* **Contact with others with jaundice**
* **Alcohol use**
* **Fever/rigors**
* **Surgery/anaesthetic history**
* **Medications**
64
What clinical signs may be present in someone with jaundice?
* **Signs of chronic liver disease**
* **Hepatic encephalopathy**
* **Lymphadenopathy**
* **Hepatomegaly**
* **Splenomegaly**
* **Ascites**
* **Palpable gallbladder**
* **Pale stool, dark urine**
65
What investigations would you consider doing in someone who presents with jaundice?
* **Bloods** - FBC; Clotting; Blood film; Haemolysis testing - retic count/coomb's; U+E's, LFTs, Total protein, Albumin, Paracetamol levels, gamma-GT, Liver screening tests
* **Ultrasound** - stones, bile ducts etc
* **MRCP/ERCP** **-** gallstones
* **Liver biopsy**
* **CT/MRI** - metastastatic disease
66
What are common causes of jaundice in someone with cirrhosis?
* **Sepsis**
* **Malignancy** - HCC
* **Alcohol**
* **Drugs**
* **GI bleeding**
67
What drugs can cause hepatocellular injury?
* **Paracetamol overdose**
* **Isoniazid, rifampicin, pyrazinamide**
* **MOAI**
* **Sodium valproate**
* **Halothane**
* **Statins**
68
What drugs can cause cholestatic jaundice?
* **Fusidic acid, Co-amoxiclav, nitrofurantoin**
* **Steroids**
* **Flucloxacillin**
* **Sulphonylureas**
* **Prochlorperazine**
* **Chlorpromazine**
69
What drugs can cause haemolytic jaundice?
Antimalarials
70
What might a AST/ALT ratio of \>/=2.5:1 indicate as a cause of deranged LFTs?
Alcoholic hepatitis
71
What might an AST/ALT ratio = 1 indicate as the cause of deranged LFTs?
Associated with ischaemia (CCF and ischaemic necrosis and hepatitis)
72
Surgical jaundice is typically..
Calcular obstructive jaundice - females, biliary colic, no weight loss, fluctuating jaundice
OR
Malignant obstructive jaundice - males, painless (vague abdo pain, less in comparison to above), weight loss, progressive jaundice
73
List the immunoglobulin tests in chronic liver disease
Raised IgA: alcohol
Raised IgG: autoimmune hepatitis or hep C
Raised IgM: PBC or hep A
74
List the autoantibodies tests in chronic liver disease
Antimitochondrial (AMA) - PBC
Anti smooth muscle (ASMA) - autoimmunehepatitis
Antinucelar factor - autoimmune hepatitis
75
Hepatitis serology tests
HepA - riased IgM
Hep B - raised sAg
Hep C - raised IgG
76
What test is done in wilson's disease?
Ceruloplasmin
77
What test is done in haemachromatosis
Raised ferritin/reduced transferrin
78
In terms of imaging, what is the first investigation you would do in jaundice?
US - is biliary tree dilated?
YES: surgical
NO: medical - do liver biopsy/blood tests (viral markers, autoantibodies)
79
List the imaging used if dilated biliary tree found on ultrasound
Need to answer two questions:
Cause of obstruction?
Level of obstruction?
* **CT**
* **detects solid massess** (pancreas and liver)
* **ERCP**
* **Used in documented CBD stones**
* **Visualises anatomy distal to obstruction**
* Diagnostic - stricture, filling defect, cytology, biopsy
* Therapeutic - stenting
* **PTC**
* **visualises anatomy proximal to obstruction**
* when ERCP not possible, US die injected into biliary tree
* Therapeutic - transhepatic placement of biliary stents
* **MRCP**
* **CBD stones/strictures**
* non inavsive assessment CBD
80
Complications of ERCP
Pancreatitis
Perforation
Bleeding (esp with sphincerotomy)
Cholangitis (prophylactic antibitoics)
81
Indications for endoscopyic ultrasound
Small \<3cm - pancreatic tumours and ampullary neoplasms
Small \<4cm - bile duct stones
82
Prior to surgical mamangement of jaundice what is given?
IV vit K - due to lack of bile in gut so body unable to absorb fat soluble vit K so vit K factor devicience (IV not IM)
Prophylactic antibiotics - risk of cholangitis
IV fluids - body sensitive to dehydration (hepatic renal syndrome)
83
Cholecocholithiasis/CBD stone management
Option 1 - ERCP - endoscopic sphincterotomy and CBD stone extraction followed by laparoscopic cholecystectomy
Option 2 - if failed ERCP - cholecystectomy, CBD exploration, stone extraction and T tube insertion
84
Management traumatic biliary sitructure (previous cholecsytectomy)
Presention is either post op jaundice or intermittent cholangitis and jaundice
Management 0 biliary stent, roux-en-Y hepatico-jejunostomy
85
Management malignant biliary strictures
Eg cholangiocarcinoa
If operable - resction and biliary reconstruction
If inoperable - CBD stent
