Liver, Biliary and Pancreatic Disease Flashcards
What is jaundice?
Yellow pigmentation of the skin or sclerae
What is jaundice caused by?
High levels of bilirubin in the body
What are the types of bilirubin?
Conjugated and unconjugated
What does un/conjugated bilirubin mean?
Conjugated bilirubin comes from the liver/biliary tree but unconjugated bilirubin is not from the liver or biliary tree
Which type of bilirubin in the blood causes the classic dark urine, itching and pale stools?
Conjugated hyperbilirubinaemia
What are two types of causes of conjugated hyperbilirubinaemia?
Obstructive jaundice - blockage of flow of bile through the bile ducts or hepatic ducts
Hepatocellular jaundice - hepatocyte damage e.g. hepatitis, cirrhosis
What are causes of obstructive jaundice?
Common - gall stones (biliary colic, cholecystits/cholangitis) pancreatic head carcinoma
Uncommon - sclerosing cholangitis, cholangiocarcinoma, chronic pancreatitis
What are the causes of hepatocellular jaundice?
Common - alcoholic hepatitis/cirrhosis, viral hepatitis, drug induced, non-alcoholic fatty liver disease
Uncommon - autoimmune liver disease, haemochromatosis, Wilson’s disease
Where is biliary colic pain?
Right upper quadrant pain
If with jaundice and fever then indicated cholangitis
What are important risk factors with liver/biliary diseases?
Alcohol intake, drug use both prescription and non prescription, travel, tattoos, blood transfusions, unprotected sexual activity
Name a cause of ascites?
Portal hypertension
What are the LFTs?
Liver enzymes
Clotting factors (prothrombin or INR)
Albumin
Give a good idea to degree of liver damage and prognosis
Which liver enzymes can you test?
ALT, AST, ALP
These are useful for diagnosis
If the rise in ALT and AST is bigger than ALP, what does this indicate?
Hepatocellular damage
If the rise in ALP is bigger than the rises in ALT and AST, what does this indicate?
Obstructive cause of jaundice
What should you ALWAYS ask in abdo exams?
Have you had any unintentional weight loss?
Which is the most common primary cancer in the biliary system (L,GB,P)?
Carcinoma of head of pancreas - should be actively excluded in patients over 40 with painless, obstructive jaundice
What is liver cancer usually caused by?
Other primary cancers, e.g lung cancer
Primary liver cancer is uncommon but can occur in those with liver cirrhosis
Which serum can you check for for primary hepatocellular cancer?
Serum alpha-fetoprotein
What would you suspect if you could palpate the gall bladder?
Cholangiocarcinoma
How much is one unit of alcohol?
10ml or 8g of pure alcohol
How do you calculate a unit?
percentage x volume (L)
4.6% x 0.568
= 2.6 units
What is the unit limit per week?
14 for men and women
What happens if someone who drinks heavily, daily, suddenly stops?
Delirium tremens.
An acute confusional state which can result in seizures and death.
How do you treat acute alcohol withdrawal?
Consider benzodiazepine or carbamazepine
Use clomethiazole as an alternative.
How do you treat delirium tremens?
Oral lorazepam as first line.
If symptoms persist offer parenteral lorazepam or haloperidol
If the bilirubin rise is not to do with the liver, what are the causes?
Increased breakdown in red blood cells, haemolysis or Gilbert syndrome?
Describe the cycle of bilirubin?
Haemoglobin is broken down into Hb, Heme and bilirubin. Albumin binds to bilirubin in the blood. This is known as unconjugated bilirubin. This travels to the liver and is taken up by a hepatocyte which conjugates the bilirubin to make it water soluble. It passes through the gall bladder then either back into systemic circulation, to the kidneys and out into the urine, or is excreted into the intestine, where bacteria attaches to it to become urobilogen, which then leaves via the urine (re-uptaken into blood) or become stercobilogen which leaves by feces.
If the levels of bilirubin are high and unconjugated, and there are no signs of liver disease, what do you think?
Pre-hepatic jaundice, haemolysis.
Do gallstones in the gallbladder cause obstructive jaundice?
No, they don’t obstruct the flow of bile in the CBD
What is sclerosing cholangitis?
A condition where you get scarring of small bile ducts in liver leading to obstruction
What does hepatitis mean??
Liver inflammation (NOT VIRAL HEPATITIS)
What is cirrhosis
Fibrosis/scarring in the liver which has led to nodule formation
What is the liver disease progress?
Damage to the liver = acute hepatitis
Then either:
–> recovery
–> chronic hepatitis –> inc. fibrosis –> cirrhosis
–> fulminant hepatitis –> transplantation/death
What are the symptoms of acute hepatitis, no matter the cause?
Typically: unwell, jaundice, RUQ pain
Severe: confusion, coagulopathy (bruising)
What would blood test be in acute hepatitis?
Typically: Raised ALT/AST, high bilirubin
Severe: coagulopathy, renal impairment
What are the symptoms of chronic hepatitis?
Typically: often none, fatigue
Usually picked up randomly from abnormal LFTs, screening, or presentation with cirrhosis
What is fulminant hepatitis?
Acute hepatitis with liver failure -
defined by encephalophathy within 28 days of jaundice
How does cirrhosis cause problems?
Portal hypertension or loss of function
What does portal hypertension cause?
Varices, piles, ascites, encephalopathy, renal failure
How does the liver adjust to change in BP?
The normal portal pressure is 10, so proportionally any change is much bigger. This is why the blood goes elsewhere - varices/piles
Why does portal hypertension cause ascites/renal failure?
Portal hypertension changes renin/AT axis, which causes lots of salt and water retention, causing fluid to leak into abdomen. When this becomes extreme, you get extreme renal artery constriction.
Why does encephalopathy come from portal hypertension?
Toxins (ammonia) that would usually be filtered by liver, escape through other varices and this causes encephalopathy - confusion, clumsiness
What does loss of function of liver cause?
Jaundice (lose ability to breakdown and deal with haemoglobin), hypoalbuminaemia, coagulopathy/bruising (can’t make clotting factors), decreased drug metabolism, decreased hormone metabolism (inc oestrogen levels hence gynacomastia, spider naevi, palmer erythema and hair loss), increased sepsis
Where is albumin made?
LIVER
Do liver function and portal hypertension come hand in hand?
NO, cirrhosis can cause either.
Does the cause of liver cirrhosis alter the symptoms?
No
What are the causes of cirrhosis of the liver?
Alcohol, Hep B + C, autoimmune liver disease, haemachromatosis, Wilson’s disease, chronic obstruction
What are the signs of liver disease?
Palmer erythema, leuconychia (decrease albumin), spider naevi, caput medusa (visible and engorged epigastric veins)
Why does a bigger increase in ALT than ALP mean it is hepatic not obstructive?
ALP is present in bile ducts, whereas ALT is present in the hepatocytes. If the hepatocytes are damaged, ALT leaks into blood stream. ALP will also increase slightly as ducts may be smaller/damaged but less so.
How do you reduce steatosis (fatty liver)?
Stop drinking, loose weight, control blood sugars
What is the first stage of an upset liver?
Steatosis
What if you ignore steatosis?
Steatohepatitis (due to too much fat)/alcohol hepatitis (alcohol)
How does alcoholic hepatitis present?
Jaundice, large tender liver, vomiting, stop drinking which then leads to alcohol withdrawal. Nightmare.
Is alcohol hepatitis always after initial damage to liver?
No, alcoholic hepatitis can occur after severe exposure to alcohol, even with absence of previous liver damage.
Is alcohol hepatitis acute or chronic?
Acute
What if you ignore steatohepatitis or alcoholic hepatitis?
Cirrhosis or death
What are the signs of cirrhosis?
Ascites, jaundice, encephalopathy, variceal bleeding
Can you reverse steatohepatitis, alcoholic hepatitis and cirrhosis?
Yes; sometimes; no
When should you consider a biopsy with ARH?
If it is severe enough to require corticosteroid treatment
How do you know if it is severe enough to warrant corticosteroid treatment?
If the Maddrey’s discriminant function is above 32 (uses prothrombin time and bilirubin to calculate score)
What is end-stage liver damage?
Cirrhosis
What does cirrhosed liver look like?
Has regenerative nodules surrounded by bands of protein - hence the bumpy feeling
What do stellate cells do?
They are between hepatocytes and sinusoids, and store vitamin A
What do stellate cells do in response to hepatocyte death?
Secrete TGF-beta and produce collagen. This collagen then grows into fibrotic scar tissue and starts to press on the sinusoid = portal hypertension.
Why do people with liver problems tremor?
Ammonia goes into the brain and can cause asterixis (tremor)
What is the clinical level of bilirubin to cause jaundice?
Above 50micromols/L
What are the three broad categories of jaundice?
Pre-hepatic
Hepatic
Post-hepatic (obstructive)
How much bile is made per day?
500-1000ml
What is bile released in response to?
Vagal response to food and CCK release
What is the pH of bile?
8-8.6
What are the two main ingredients of bile?
Bile pigments (haemoglobin breakdown products) and bile salts (derived from cholesterol)
When bilirubin becomes conjugated, what joins it?
Glucuronic acid
What is haemolytic jaundice?
A type of pre-hepatic jaundice which is due to haemolysis (breakdown of RBC). Can be due to: RBC abnormality e.g sickle cell Incompatible blood transfusion Drug reaction Hypersplenism
How does haemolysis cause jaundice?
Extra breakdown of RBC means more bilirubin and so the glucuronyl transferase is saturated - liver compensates by producing more conjugated bilirubin, hence dark stools.
What is a main sign of haemolytic jaundice?
No bilirubin in urine
The amount of dark urine and pale stools varies with how much obstruction the injury is causing.
What are some causes of hepatocellular jaundice?
Infection
Cirrhosis due to alcohol
Cirrhosis secondary to steatohepatitis (NASH)
Damage by drugs or toxins
Why do you get pale stools in obstructive jaundice?
The conjugated bilirubin cannot make its way to the intestine due to a blockage, therefore no stercobilinogen or urobilinogen can be made and excreted.
THIS ALWAYS OCCURS.
What are important questions to ask a jaundiced adult?
Drug and alcohol history, cigarette use, foreign travel and sexual activity
What is Troisier’s node?
Left supraclavicular node enlargement
Where, particularly, do you look for muscle wasting for evidence of malignancy?
The arm muscles (between thumb and forefinger)
How do we investigate a patient with jaundice?
- Trans-abdo ultrasound. Looking for evidence of dilated bile ducts. If normal then hepatocellular or prehepatic, if not then —>
- CT
- ERCP endoscopic retrograde cholangiopancreatography
This looks for stones.
How do you tell if there is contrast in CT?
If the aorta is white.
What results would you get back from urine and blood tests in obstructive jaundice?
Raised plasma bilirubin
Raised conjugated bilirubin
Bilirubin glucoronide in urine
Marked raised ALP
What results would you get back from urine and blood tests in hepatocellular jaundice?
Raised plasma bilirubin Raised conjugated bilirubin Bilirubin glucuronide in urine Raised transaminase Mild raise in ALP
What results would you get back from urine and blood tests in obstructive jaundice?
Raised plasma bilirubin
Name some infective causes of liver disease
Epstein Barr virus (EBV)
cytomegalovirus (CMV)
Hep A, B or C
Name some lifestyle causes of liver disease
Alcohol excess, obesity, diabetes mellitus
Which drugs can cause liver disease?
Methotrexate, flucloxacillin, rifampicin, anti-epileptics, paracetamol overdose
What are some autoimmune causes of liver disease?
Autoimmune hepatitis, primary billiary cholangitis, primary sclerosing cholangitis
Name some hereditary causes of liver disease.
Hereditary haemochromatosis, alpha-1-antitrypsin deficiency
If someone has upper right abdominal pain, what could be the DDs?
Structures above the diaphragm: pleuritic pain, inferior MI
Structures below the diaphragm:
Liver, gall bladder, pancreas, bowels, kidneys
What’s the normal surface anatomy of liver?
4th ICS to costal margin
What’s the difference in examination between liver cirrhosis and metastasises in liver?
Metastasis are painful, but cirrhosis is not (upon palpation)
What is capital medusa?
Blood flow back into umbilical vein
Name four signs of portal hypertension
Caput medusa, splenomegaly, oesophageal varices, ascites
What does the portal vein drain?
All GI organs from distal oesophagus to rectum
Which metabolic disturbances can precipitate chronic liver disease?
Hypoglycaemia, renal failure
Why can constipation cause liver disease?
Bacteria sit and fester in the GI, which get absorbed and drain into the liver
How can we get rid of constipation?
Lacterose, enema
How does ascites fluid change with diagnosis?
Get ratio of albumin in serum to albumin in ascites.
What is a transudate fluid vs exudate?
Exudate fluids have more protein than serum has.
Transudate fluids have less protein than serum.
So the ratio for exudate would be lower than 1.1
The ratio for transudate would be higher than 1.1
What are causes of transudate fluid in the peritoneum?
- Liver failure e.g. cirrhosis with portal hypertension
- Congestive cardiac failure
- Nephrotic syndrome
SAAG >1.1g/L
What are some causes of exudate fluid in the abdomen?
- Malignancy (liver or metastases)
- Peritonal TB
Cells are leaky.
SAAG <1.1g/L
Is ascetic fluid is mor than 500 microlitres what is the diagnosis of that?
Spontaneous, bacterial peritonitis
What is a good symptom of autoimmune liver diseases?
Severe itching, pruritis
Which is PBC?
Autoimmune, antibodies to mitochondria, pruritis, mainly female (5-10x)
Which antibody do you get with chronic active hepatitis?
Anti-smooth muscle antibodies
Which are the most common viral hepatitis strains?
A and B
Which type of bilirubin is increased in hepatocellular jaundice?
Unconjugated bilirubin
Which aminase is raised in hepatocellular jaundice?
ALT
What is neonatal jaundice?
Jaundice at birth (>85micromoles/L) - occurs in 60% of term infants and 80% preterm
Physiological/pathological if unconjugated hyperbilirubinaemia because it is non-toxic unless it crosses the BBB
Pathological if conjugated hyperbilirubinaemia
What are important questions in history of jaundice?
Pain?
Duration
Itching
Colour of urine and stools
Which viral hepatitis never becomes chronic?
Hep A
What is the duration, spread mode, serology and outcome of Hep A?
DURATION: Acute —> Recovery (99%) or Fulminant hepatitis (1/2%)
<12 weeks
SPREAD: Faeco-oral, developing world, immunisation for travellers and w/liver disease
SEROLOGY:
3 wk incubation, IgM high in acute, IgG high later and stays high post infection
OUTCOME: Treatment is not needed unless fulminant
What is the duration, spread mode, serology and outcome of Hep B?
DURATION: Acute –> Recovery (96%), chronic (3%) (—>cirrhosis & cancer) or fulminant (1%). Chance of chronic increase with youth, immunosuppressed, genotype and route of infection.
SPREAD: Blood, sex, IVDU, more than 1bill are exposed, +10% in far east, immunisation is possible
SEROLOGY:
Acute: HBsAg goes up early with IgM high, then IgG high and IgM low. Then antibodies to HBsurface appear when recovered.
Chronic: HBsAG high and IgG high. If HbeAg is +ve then immunotolerant & infectious. If HbeAB +ve then immunoreactive, less infectious.
OUTCOME: Younger age of infection, immunosuppressed and genotype = more likely to be chronic.
Antiviral treatment, interferon
What can Hep B cause?
Primary liver cancer (6th most common in world).
A male with hep B caused liver cirrhosis has a 5=10% chance of developing lung cancer in a year
What are the specifics re age and chronicity of Hep B?
<1 year = 90%
1-5 yrs = 30%
>5 yrs = 1-5%
What determines whether you will progress on to cirrhosis and cancer in Hep B?
Rate of fibrosis progression with a high viral load. Biopsy score (0-6) 0=no fibrosis, 6=cirrhosis
If someone is immunotolerant of Chronic Hep B, what does that mean?
They have high HBsAg for >6months, they are infectious but with few problems and normal LFTs
If someone is immunoreactive of Chronic Hep B, what does that mean?
They have high HBsAg for >6months, they are not very infectious but have high ALT and are often fibrotic/cirrhotic.
How do we treat Hep B?
Not needed for acute.
Chronic can be treated with a lifetime antiviral - tenofovir, entecavir, adefovir or lamivudine - OR an interferon.
What is the duration, spread mode, serology and outcome of Hep C?
DURATION:
SPREAD: blood, IVDU, sexual, medical, tattoo, no immunisation possible.
What is Gilbert’s syndrome?
Low levels in bilirubin breakdown enzymes so bilirubin isn’t conjugated and high levels of unconjugated bilirubin end up in the blood
What are the causes of pre-hepatic jaundice?
Haemolytic anaemia
Gilbert’ts syndrome
What are the blood results for pre-hepatic jaundice?
Raised levels of unconjugated bilirubin
All else normal
Normal wee
Normal poo
What are the blood results for hepatic jaundice?
Raised levels of conjugated and unconjugated bilirubin
Dark urine (conjugated bilirubin)
Normal stools
Increased LFTs
What are the blood results for post-hepatic jaundice?
Raised conjugated, normal unconjugated bilirubin
Dark urine
Pale stools
Increased LFTs
