HPB Medicine Flashcards
1
Q
What is hepatitis?
A
Inflammatory disease of the liver, which can be acute or chronic
2
Q
What are the acute causes of hepatitis?
A
Viral infections (hepatitis A-E / non A-E infections)
Autoimmunen
Drug reacitons
Alcohol
3
Q
What are the chronic causes of hepatitis?
A
Hepatitis B +/- Hepatitis D Hepatitis C Autoimmune hepattis Alcohol Hyperlipidaemia (NAFLD) Drugs (methyldopa /nitrofurantoin)
Metabolic disorders (Wilson’s disease, alpha-1-antitrypsin deficiency, haemochromatosis)
4
Q
What are the components of a liver screen?
A
Microbiology: Viral screen
Clinical chemistry: ferritin/transferrin, lipids, caeruloplasmin, AFP, alpha-1-antitrypsin
Immunology: autoantibodies
Abdominal USS
5
Q
What type of virus is hepatitis A?
A
RNA picorna virus
6
Q
How is hepatitis A transmitted?
What is the incubation period?
A
feco-orally
Incubation period is 2-6 weeks
7
Q
What type of disease does Hepatitis A lead to?
A
80% = asymptomatic and naturally cleared
Does not lead to chronic liver disease and thus there are no carriers
Typically affects children / young adults
8
Q
What is the treatment for hepatitis A?
A
No specific treatment, mortality 0.1%
9
Q
What type of virus is hepatitis E?
A
RNA calcivirus
10
Q
How is hepatitis E transmitted?
A
Feco-orally
11
Q
What type of disease does hepatitis E lead to?
A
Similar to hepatitis A infection Epidemics of acute, self-limiting hepatitis with no progression to chronic disease
Common in indo-china, so consider if recent travel
Can cause severe disease in pregnant women
12
Q
What kind of virus is hepatitis B?
A
Hepa-DNA virus, transmitted in the blood, semen and saliva via skin breaks or mucous membranes
Vertical transmission
13
Q
What is the incubation period of hepatitis B?
A
1-6 months
14
Q
Describe the structure of hepatitis B?
A
Inner core (HBcAg) surrounded by an outer envelope of surface protein (HBsAg)
15
Q
Does Hepatitis B cause chronic disease?
A
Yes - around 10% of those infected will develop chronic disease and 1% will develop fulminant liver disease
16
Q
What is the structure of hepatitis D?
A
Incomplete RNA virus, that can only cause infection in the presence of Hep B as it requires the Hep B virus for its own assembly
17
Q
How is hepatitis D transmitted
A
Also transmitted by bodily fluids and can be both acute or chronic
Can be acquired simultaneously with Hep B or occur later
Patients with hepatitis D superadded to hepatitis B infection are more likely to develop fulminant liver disease
18
Q
What is the structure of Hepatitis C?
A
RNA flavivirus, clinically similar to Hep B infection
19
Q
How is hepatitis C transmitted?
A
Via bodily fluids - particularly common in IVDUs
Vertical transmission is rare and sexual transmission is uncommon
20
Q
What are the long term effects of Hepatitis C?
A
85% become chronically infected
and 30% get cirrhosis in 20 years
21
Q
For which hepatitis strains are there vaccines for?
A
Vaccines for A and B but not C
22
Q
What are ‘non A-E infections’?
A
hepatotropic viral infections that cannot be typed
23
Q
Describe the morphology of acute hepatitis?
A
Hepatocytes undergo degenerative changes (swelling and vacuolation) before necrosis and rapid removal
Necrosis is usually maximal in zone 3, as this is centrilobular and thus receives the least oxygenated blood
Extent can vary from scattered necrosis to multiracial necrosis leading to fulminant hepatic failure
24
Q
What is chronic hepatitis?
A
Any hepatitis lasting more than 6 months
principal cause of chronic liver disease, cirrhosis and hepatocellular carcinoma
25
Describe the pathology of chronic hepatitis?
Chronic inflammatory cell infiltrates are present in the portal tracts
There may also be a loss of definition of the portal/periportal limiting plate, confluent necrosis and fibrosis
This eventually leads to cirrhosis
The overall severity is judged by the degree of inflammation and the extent of fibrosis / cirrhosis (staging), using various scoring systems such as the Child Pugh score
26
What is HbsAg?
Hepatitis B surface antigen
Marker of viral replication and thus ACTIVE infection
27
When does HbsAg appear and disappear?
Appears within 6 weeks of infection, disappears by 3 months after
28
What is HbsAb?
Anti-hepatitis B surface antibody
Marker of previously cleared infection / vaccination
29
What is HBeAg?
Hepatitis B E antigen
| Marker of a high degree of viral replication (infectivity)
30
What is HBeAb
Hepatitis B e antibody
| Marker of natural immunity to hepatitis B
31
What is HBcAb IgG?
Anti-hepatitis B core IgG antibody
| Non-specific marker of current / previous infection (persists after 6 months)
32
What is HbcAb IgM?
Anti-hepatitis B core IgM antibody
| Infection within the last 6 months (acute viral hepatitis)
33
What is HBV PCR?
The best marker of viraemia?
34
What markers indicate the immune tolerance phase?
HBsAg / HbeAg and PCR positive, transaminases negative
35
What markers indicate acute hepatitis?
All markers positive except HbsAb
36
What markers indicate chronic hepatitis?
All markers positive for >6 months
LFTs less deranged
HbeAg will be positive, and HbeAb negative
37
What markers indicate natural immunity?
HbsAg negative, HbsAb positive
HBcAb IgG positive, IgM negative
HbeAg negative, HBeAb positive
38
What markers indicate vaccination?
HbsAg negative, HbsAb positive
| HbcAb NEGATIVE, HbeAb negative
39
What is the presentation of acute viral hepatitis?
Pre-icteric phase:
1-2 week prodrome of malaise, arthralgia, headache and anorexia
Classic aversion to cigarette smoke
Vague RUQ pain
Icteric phase: patient becomes icteric with associated pale stools and dark urine, pruritus and skin rash
May be associated lymphadenopathy, plus hepato/splenomegaly
Hepatitis A and C often cause very mild or no symptoms
Extra-hepatic features more common in hepatitis B
40
What is the presentation of acute alcoholic hepatitis?
Presents after a binge with jaundice, RUQ pain and systemic upset
There may be signs of chronic liver disease (acute on chronic presentation)
41
What tests predict survival in acute hepatitis?
Bilirubin, prothrombin time and hepatic encephalopathy
| combined - discriminant function
42
What discriminant function does acute alcoholic hepatitis carry?
>32 (discriminant function is bilirubin, prothrombin time and hepatic encephalopathy)
mortality here is >50% (consider steroids, monitor closely)
43
What does AST:ALT >2.0 suggest?
Alcoholic liver disease
| AST --> AStella Artois haha
44
What does autoimmune hepatitis most commonly present as?
Acute hepatitis
Up to 40% patients manifest as acute hepatitis with jaundice
Non-specific symptoms of tiredness, arthralgia, fevers and weight loss
45
What are the age peaks for autoimmune hepatitis?
15-25 or perimenopausal ages
46
What investigations can be done for autoimmune hepatitis?
High transaminases and immunoglobulin (IgG) levels
Negative viral serology
High titres of autoantibodies (non-specific, e.g. ANA, ASMA). Final diagnosis is via liver biopsy
47
What are the symptoms of chronic hepatitis?
often asymptomatic unless complications such as cirrhosis develop
Can only be diagnosed when serum ALT levels are elevated for over 6 months (e.g. on follow up for acute viral hepatitis diagnoses)
48
What are the treatment options for autoimmune hepatitis?
Prednisolone 30mg O.D
Add azathioprine 1mg/kg/day after TMPT assays
If there are falls in transaminases, gradually reduce the prednisolone dose to maintain the fall (to 10mg/day over 4 weeks)
Long term therapy with low-dose prednisolone (5-10mg) and azathioprine is then recommended
Bone protection plus monitoring required
49
What is the management of acute hepatitis B?
Supportive therapy and alcohol avoidance (95% will recover and develop immunity)
First line management is with subcutaneous peginterferon-alfa-2a for 48 weeks (NICE)
50
What is the management of Hepatitis C?
New drugs on the market
| Very specialist
51
How is liver biopsy performed?
Needly biopsy, USS/CT, laparoscopic
52
What are the indications for liver biopsy?
Chronic hepatitis, cirrhosis, suspected neoplastic disease, storage diseases or unexplained hepatomegaly
53
What are the contraindications for liver biopsy?
Prolonged PT
Platelet count <80
Ascites
Extra hepatic cholestasis
54
What are the complications of liver biopsy?
abdominal / shoulder pain and minor intraperitoneal bleeding
Rarer complications: haemothorax, pleurisy, haemobilia, biliary peritonitis
55
What are the newer alternatives to liver biopsy?
Fibroscan (transient elastography) which allows the liver stiffness to be measured non-invasively
This score can be used to stage fibrosis
Non invasive: MR elastography and serum biomarker tests
56
Which drugs are more likely to cause chronic hepatitis?
Methyldopa, nitrofurantoin, minocycline, lisinopril and diclofenac
57
Is paracetamol an intrinsic or extrinsic hepatotoxin?
Intrinsic
58
How does paracetamol metabolism happen normally?
At therapeutic doses, it is conjugated with glucuronide and sulphate
Small amount it metabolised by mixed function oxidase systems to form N-acetyl-p-benziquinoneminime (NAPQI)
NAPQI immediately conjugated with glutathione due to its toxicity
59
What happens in paracetamol overdose?
Normal conjugation pathways become saturated, meaning large amounts of NAPQI are created
This overwhelms the liver glucothione stores to cause cellular damage. Severity is dose related, however, malnourished individuals / those with high alcohol intake appear to be more susceptible
60
What is the presentation of paracetamol overdose?
```
Most remain asymptomatic for 24h or at most develop anorexia, nausea and vomiting, then symptoms after 24h:
RUQ pain
Metabolic acidosis
Hypotension
Hypoglycaemia
Pancreatitis
Arrhythmias
```
61
Describe the pattern of liver damage following overdose with paracetemol
Not detectable on blood tests until 18 hours after ingestion
Damage peaks at 72-96 hours post-ingestion (deranged ALT/ALP and INR)
Without treatment, some will develop fulminant liver failure
Renal failure due to acute tubular necrosis can also occur
62
What is the management for paracetamol overdose?
A-E assessment
Lavage if >12g (>150mg/kg in children) taken within 1 hour
Activated charcoal if <1 hour insect ingestion
Take bloods 4 hours post ingestion: INR, ABG, LFTs, U&Es, glucose, blood salicylate and paracetamol level
N-acetyl-cysteine if meets treatment threshold
Stop when plasma paracetemol levels return below the treatment line and patient is asymptomatic with normal biochemistry
63
How does N-acetylcysteine work?
Replenishes cellular glucothione stores and may repair oxidative damage
Can cause rash, oedema, hypotension and bronchospasm in 5% but these are rarely serious and these can be treated with IV chlorphenamine
64
What is the alternative to N-acetyl-cysteine?
Oral methionine
can only be used up to 12 hours post ingestion
Unreliable if vomiting, or activated charcoal has been used
65
What is the lifespan of a RBC?
| What happens to RBC at the end of their lifespan?
120 days
Destroyed in the reticuloendothelial system of the spleen
66
What happens to haem following destruction?
Haem --> biliverdin --> bilirubin (insoluble/indirect bilirubin) which is bound by albumin in the plasma
Bilirubin can be taken up by hepatocytes and conjugated to bilirubin gluconide by glucuronyl transferase
67
What happens to bilirubin gluconide (soluble bilirubin)?
Excreted in the bile into the bowel lumen, where it is transformed by bacteria to urobilinogen
Most urobilinogen is excreted in the stools to give it the dark colour (aka stercobilinogen)
68
What happens to urobilinogen?
Small amount is reabsorbed from the intestine into the portal venous tributaries and passes back to the liver, where most of it is excreted once more into the gut
Some of this reabsorbed urobilinogen reaches the systemic circulation, and this is excreted by the kidney into the urine
When the urobilinogen in the urine is exposed to air, it is oxidised to urobilin to give urine a dark colour (why urine goes dark when u don't flush)
69
What is jaundice and when does jaundice arise?
Yellowing of the skin
Usually when the bilirubin level reaches 50micromol/L with the upper limit of normal being 25
70
What is the cause of pre-hepatic jaundice?
Occurs secondary to increased erythrocyte breakdown e.g. in haemolysis or reabsorption of a large haematoma
Haemolytic anaemia
Gilbert’s syndrome
Criggler-Najjar syndrome
The bilirubin has not yet been processed by the liver, thus is mainly unconjugated in the blood
71
What is the cause of cholestatic jaundice?
There is an obstruction to bile outflow from the liver, leading to 'cholestasis'
72
Is cholestatic jaundice conjugated or unconjugated?
Bilirubin has been processed by the liver, so mainly conjugated
73
What is the effect of cholestatic jaundice on urine and stool?
Can enter the urine giving dark urine
| Cannot enter the GIT and is not excreted in faeces, so you get pale stools
74
What is intrahepatic obstruction?
Obstruction of the hepatic bile canniliculi
Can occur due to multiple different causes including:
hepatitis
cirrhosis
neoplasm
Drugs (chlorpromazine, flucloxacillin, isoniazid, OCP)
Pregnancy
75
What is extra hepatic obstruction?
Obstruction of the hepatic ducts, or biliary tree
Causes within the lumen: gallstones
Causes within the wall: cholangiocarcinoma, primary sclerosing cholangitis, congenital atresia of the common bile duct
External causes: pancreatitis, tumour of the pancreatic head
76
What is hepatocellular jaundice?
There is an issue with the cells of the liver, leading to dysfunction and a partial inability to conjugate bilirubin
This leads to mixed conjugated / unconjugated bilirubin in the blood
If severe, there can be a total inability to conjugate bilirubin and an unconjugated hyperbilirubinaemia?
77
What are the causes of hepatocellular jaundice?
Alcoholic liver disease
Viral hepatitis
Iatrogenic, e.g. medication: paracetamol, methyldopa
Hereditary haemochromatosis
Autoimmune hepatitis
Primary biliary cirrhosis or primary sclerosing cholangitis
Hepatocellular carcinoma
78
What is the cause of isolated unconjugated hyperbilirubinaemia, with no evidence of liver damage?
Gilbert's syndrome
79
What is Gilbert's syndrome?
Congenital lack of glycoronyltransferase
affects up to 7% of the population
Of no clinical significance but can lead to transient episodes of jaundice, particularly following an infection such as URTI
Serum unconjugated bilirubin will be raised, but LFTs and reticulocytes normal
80
Describe the appearance of stool in prehepatic jaundice?
Large amounts of bilirubin excreted into gut, thus stercobilinogen is raised to give normal / dark stools
Urinary urobilinogen is thus also raised due to greater re-absorption, which can be tested for, but clinically there will not be dark urine as urobilinogen is not dark in colour until oxidised
81
What is the appearance of stool in obstructive / cholestatic jaundice?
Very little bile can enter the gut, thus stercobilinogen low, giving pale stools
As such, there is no urinary urobilinogen as there is no enterohepatic recycling
AS bilirubin is conjugated in teh blood, urinary bilirubin is present, giving dark urine
82
What is the appearance of stools and urine in hepatocellular jaundice?
Can present with elements of both prehepatic and cholestatic jaundice:
Urinary urobilinogen may also be raised in hepatocellular jaundice, due to the inability of the liver to re-excrete urobilinogen reabsorbed from teh bowel
Bilirubin may be present if conjugated bilirubin levels are high enough, giving dark urine
Stools may be paler than usual, due to a decrease in teh ability to conjugate bilirubin and thus excrete it into the gut
83
What investigations can be done for jaundice?
Bloods: FBC, reticulocytes, LFTs, U&Es, clotting, glucose, bilirubin levels
Transaminases most raised in hepatocellular jaundice / intrahepatic obstruction
ALP most raised in extra hepatic cholestasis
Glucose may be low in liver failure, or raised in pancreatic disease
Urinary urobilinogen/bilirubin
84
What further investigations can be done for jaundice?
Blood films / Coomb's test if suspecting prehepatic jaundice
Viral serology / autoantibodies: if suspecting hepatitis
USS: Will show dilated duct system to confirm obstruction / gallstones
MRCP: non-invasive high resolution imaging of the biliary tree
CT/MRI: useful to demonstrate intrahepatic lesions , which may need to be accurately needle biopsied
Can also show pancreatic lesions
Needle biopsy: can give important info with regard to hepatic pathology
Prothrombin time should be corrected first if deranged (with FFP/platelets)
85
What is ERCP?
Endoscopic retrograde cholangiopancreatography
If the ductal system is dilated, the ampulla of Vater is cannulated using an endoscope, and contrast is injected to demonstrate lesions
This should only be used therapeutically
86
What should be given prior to ERCP?
Ciprofloxacin as antibiotic prophylaxis with sedation and analgesia prior to procedure
87
What are the complications of ERCP?
Pancreatitis, perforation or cholangitis (give IV abx before)
Post op bleeding
88
What is PTC?
Percutaneous transhepatic cholangiography
Percutaneous cannulation of a dilated bile duct within the liver, generally used for therapeutic intervention if ERCP is not possible
Can be used to stent obstructing bile duct lesions, but does not allow ampulla/pancreatic duct to be visualised
