Gall Bladder Pathology

Question 1

Describe the pathophysiology of PBC [+]

Answer 1

PBC:
- inflammation and damage to the epithelial cells of the bile ducts (the cholangiocytes)
- can lead to obstruction of bile flow through these ducts. Reduced flow of bile is called cholestasis.
- The back-pressure of bile and the overall disease process ultimately lead to liver fibrosis, cirrhosis and failure
- Raised bile acids cause itching, and raised bilirubin causes jaundice

Question 2

Why are PBC patients at risk of atherosclerosis? [1]

Answer 2

Bile acids, bilirubin and cholesterol are excreted through the bile ducts into the intestines. When obstruction to the outflow of these chemicals means they are not being excreted,

Raised cholesterol causes cholesterol deposits in the skin called xanthelasma. Xanthomas are larger nodular deposits of cholesterol in the skin or tendons. Raised cholesterol increases the risk of atherosclerosis and cardiovascular disease.

Question 3

Describe the stool and urine colour in PBC [1]

Answer 3

Bilirubin is responsible for the darker colour of stools. A lack of bilirubin results in pale stools. Excretion of bilirubin via the urine causes dark urine.

Question 4

Describe the signs and symptoms of PBC [+]

Answer 4

The typical patient is a white woman aged 40-60 years. Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with:
* Fatigue
* Pruritus (itching)
* Gastrointestinal symptoms and abdominal pain
* Jaundice
* Pale, greasy stools
* Dark urine

On examination, there may be:
* Xanthoma and xanthelasma (cholesterol deposits)
* Excoriations (scratches on the skin due to itching)
* Hepatomegaly
* Signs of liver cirrhosis and portal hypertension in end-stage disease (e.g., splenomegaly and ascites)

Question 5

Describe the investigations and findings conducted for PBC [4

Answer 5

TOM TIP: The two results for primary biliary cholangitis to remember are anti-mitochondrial antibodies and alkaline phosphatase

• Raised ALP
• Raised IgM
• AMA antibodies
• ANA antibodies (30%)

Question 6

State and describe the MoA of the first choice drug used to treat PBC [1]

What is the second line drug? [1]

Which drug can you use to treat the itchiness? [1]

Answer 6

Ursodeoxycholic acid is the most essential treatment to remember in primary biliary cholangitis.
- It is a non-toxic, hydrophilic bile acid that protects the cholangiocytes from inflammation and damage. It makes the bile less harmful to the epithelial cells of the bile ducts. It slows the disease progression and improves outcomes.

Obeticholic acid:
- (where UDCA is inadequate or not tolerated – although it can have significant adverse effects)

Cholestyramine:
- Pruritus

Question 7

What are the three main risks of PBC? [3]

Answer 7

• Cirrhosis
• Osteomalacia and osteoporosis
• Significantly increased risk of hepatocellular carcinom

Question 8

Describe the pathophysiology of PSC [1]

Answer 8

Chronic, progressive, cholestatic liver disease characterized by inflammation, fibrosis, and destruction of the intrahepatic and/or extrahepatic bile ducts, leading to the development of multifocal bile duct strictures.

This causes obstruction of bile, leading to back pressure of bile into the liver - hepatatis and cirrhosis

Question 9

How does PSC present? [1]

Answer 9

Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with:
* Abdominal pain in the right upper quadrant
* Pruritus (itching)
* Fatigue
* Jaundice
* Hepatomegaly
* Splenomegaly

Question 10

Which blood results indicate PSC? [3]

Answer 10

elevated alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels

p-ANCA may be positive

Question 11

How do you investigate (aside from blood tests) [2]

Answer 11

MRCP (or ERCP): show a ‘beaded appearance

Colonoscopy should be performed to assess for ulcerative colitis.

Liver biopsy is not usually required but may be used where there is diagnostic uncertainty.

Question 12

Describe how you manage PSC? [4]

Answer 12

Endoscopic retrograde cholangio-pancreatography (ERCP):
- treat dominant strictures by dilatation & placing stents

Antibiotics are given alongside ERCP to reduce the risk of infection (bacterial cholangitis)

Colestyramine:
- for symptoms of pruritus (a bile acid sequestrant that reduces intestinal absorption of bile acids)

Replacement of fat-soluble vitamins

Question 13

What are two complications that PSC patients are at risk of ? [2]

Answer 13

cholangiocarcinoma (in around 10%)
increased risk of colorectal cancer

Question 14

TOM TIP: Explain why you should advise patients to avoid eating fatty foods if they have gall stones [1]

Answer 14

TOM TIP: Fat entering the digestive system causes cholecystokinin (CCK) secretion from the duodenum. CCK triggers contraction of the gallbladder, which leads to biliary colic.

Patients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction. Exams may test this mechanism, so it is worth remembering.

Question 15

Raised bilirubin might be caused by an obstruction to the gall bladder. Name three causes of why this may occur [3]

Answer 15

• gallstone in the bile duct
• cholangiocarcinoma
• tumour of the head of the pancreas

Question 16

An [] is a useful first-line investigation for symptoms of gallstone disease, for example, abdominal pain, right upper quadrant pain and jaundice. It is the most sensitive initial imaging test for gallstones

Answer 16

An ultrasound scan is a useful first-line investigation for symptoms of gallstone disease, for example, abdominal pain, right upper quadrant pain and jaundice. It is the most sensitive initial imaging test for gallstones (CT scans are not good at identifying gallstones or biliary disease).

Question 17

What US findings would indicate acute cholecystitis? [1]

Answer 17

Acute cholecystitis:thickened gallbladder wall, stones or sludge in gallbladder and fluid around the gallbladder

Question 18

What investigational tool would you use if US doesnt show a detailed picture in gall stone path? [1]

Answer 18

Magnetic Resonance Cholangio-Pancreatography

Question 19

Name three complications of ERCP use [3]

Answer 19

Excessive bleeding
Cholangitis (infection in the bile ducts)
Pancreatitis

Question 20

What scar would indicate that a cholecystectomy has occured? [1]

Answer 20

Kocher

Question 21

Describe when and how you treat biliary colic [2]

Answer 21

Symptomatic management and prevention:
- Analgesia: Simple pain relief with paracetamol and NSAIDs (in the absence of contra-indications). Occasionally opioid analgesia may be required.
- Diet: A low-fat diet may be trialled with some patients experiencing a significant reduction in the number and severity of episodes.

Surgical management:
- Cholecystectomy - a routine general surgery review with a view to considering operative management should be arranged. In patients with significant co-morbidities, a cholecystectomy may represent unacceptable risk and as such conservative measures trialled.

Question 22

Describe the managment of biliary colic if CBD stones are detected from US [2]

Answer 22

Prior to cholecystectomy it is key that CBD stones are excluded.

All patients will have had an USS and set of LFTs as a minimum

If there is suspicion of CBD stones (e.g. dilated CBD or CBD stone on USS, raised bilirubin on LFTs) then there are two main options:
- MRCP +/- ERCP: MRCP allows for confirmation of stones in the biliary tree. If present ERCP allows for therapeutic intervention with stone retrieval, sphincterotomy and stent placement prior to cholecystectomy.
- On-table cholangiogram: Less commonly available and technically challenging. During the laparoscopic cholecystectomy the bile duct is intubated to allow the injection of dye with fluoroscopy in-theatre to diagnose stones in the biliary tree. Various techniques may then be used to retrieve/expel stones.

Question 23

Describe what is meant by acute cholecystitis [2]

Answer 23

Inflammatory condition of the gallbladder, typically precipitated by the obstruction of the cystic duct due to gallstones (cholelithiasis).

It is a key complication of gallstones, and the majority of cases (around 95%) are caused by gallstones (calculous cholecystitis).

Question 24

Which two locations do gall stones get lodged to cause acute cholecystitis? [2]

Answer 24

Gallstones may be trapped in the neck of the gallbladder or in the cystic duct.

Question 25

Name a scenario where acalculous cholecystitis occurs

Answer 25

patients on total parental nutrition or having long periods of fasting (for example in ICU for other serious conditions), where the gallbladder is not being stimulated by food to regularly empty, resulting in a build-up of pressure

Question 26

Describe a clinical sign used to suggest acute cholescystitis

Answer 26

Murphy’s sign is suggestive of acute cholecystitis:
* Place a hand in RUQ and apply pressure
* Ask the patient to take a deep breath in
* The gallbladder will move downwards during inspiration and come in contact with your hand
* Stimulation of the inflamed gallbladder results in acute pain and sudden stopping of inspiration

Question 27

Describe how you investigate for Acute. Chole [2].

Describe what results would suggest this pathology for the above ^ [3]

Answer 27

Ultrasound is the first-line investigation of choice:
* Thickened gallbladder wall
* Stones or sludge in gallbladder
* Fluid around the gallbladder

Magnetic resonance cholangiopancreatography (MRCP):
- may be used to visualise the biliary tree in more detail if a common bile duct stone is suspected but not seen on an ultrasound scan (e.g., bile duct dilatation or raised bilirubin).

Question 28

Describe the management of acute cholescystitis [3]

Answer 28

Conservative management involves:
* Nil by mouth
* IV fluids
* Antibiotics (as per local guidelines)
* NG tube if required for vomiting

Endoscopic retrograde cholangio-pancreatography (ERCP) can be used to remove stones trapped in the common bile duct.

Cholecystectomy (removal of the gallbladder) is usually be performed during the acute admission, within 72 hours of symptoms. In some cases, it may be delayed for 6-8 weeks after the acute episode to allow the inflammation to settle.

Question 29

Describe the complications of acute chole [4]

Answer 29

Gangrenous cholecystitis
* occurs in up to 20% of patients

perforation
* occurs in up to 10% of patients
may result in either a pericholecystic abscess or peritonitis

cholecystoenteric fistula
* usually seen with chronic cholecystitis
* results in air in the biliary tree (pneumobilia)
* if a gallstone passes through the fistula may result in gallstone ileus

Question 30

Describe how you manage gall bladder empyema [2]

Answer 30

Question 31

TOM TIP: Painless jaundice should make you think of [] or cancer of the [].

Which is more likely? [1]

Answer 31

TOM TIP: Painless jaundice should make you think of cholangiocarcinoma or cancer of the head of the pancreas.

Pancreatic cancer is more common, so this is likely the answer in your exams.

Question 32

Which tumour marker is used for cholangiocarcinoma? [1]

Answer 32

CA 19-9 (carbohydrate antigen) is a tumour marker that may be raised in cholangiocarcinoma. It is also raised in pancreatic cancer and a number of other malignant and non-malignant conditions.

Question 33

Charcot’s triad = ? [3]
Reynold’s pentad = ? [5]

Answer 33

Charcot’s triad:
- fever, jaundice and right upper quadrant pain

Reynold’s pentad:
- + septic shock and mental confusion

Question 34

Describe different causes of ascending cholangitis [4]

Answer 34

Cholelithiasis leading to → choledocholithiasis

Malignant strictures
* Primary biliary tumours (cholangiocarcinoma)
* Primary gallbladder / ampullary cancer
* Pancreatic cancer

PSC

Iatrogenic biliary tract injury, commonly seen in cholecystectomy can lead to benign strictures

Chronic pancreatitis leads to stenosis and stricture of the common bile duct

Question 35

Describe the pathophysiology of asending cholangitis [3]

Answer 35

The pathophysiology of ascending cholangitis typically begins with obstruction of the common bile duct due to gallstone, stricture or malignancy → bacterial seeding of the biliary tree via the portal vein & retrograde migration of bacteria from the duodenum up the biliary tree

Additionally, biliary pressure increases (>20cmH20) due the obstruction → pressure gradient that promotes bacterial extravasation into the blood stream and indirectly inhibits macrophage release from Kupffer cells → bacteraemia.

Bacteraemia gives rise to systemic inflammatory response syndrome (SIRS)

Question 36

Describe how stools appear in ascending cholangitis [1]

Answer 36

Grey / clay coloured stools due to decreased bile secretion into the small bowel

Question 37

What’s important to note about patients with an indwelling stent and ascending cholangitis presentation [1]

Answer 37

It is important to note that those with an indwelling bile duct stent may not develop jaundice as a clinical feature.

Question 38

Describe how ascending cholangitis would present on a FBC [5]

Answer 38

FBC:
- WCC will be >10 x109/L
- Prothrombin time will be raised with sepsis
- Deranged LFTs are often seen with hyperbilirubinaemia and elevated serum alkaline phosphatase
- Often decreased K+ and Mg2+
- CRP is almost always raised and indicative of inflammation
- Blood cultures: Positive in 20-70% of cases

Question 39

How do you investigate for ascending cholangitis with imaging?

Answer 39

Endoscopic retrograde cholangiopancreatography (ERCP):
-Best first intervention in patients with known history of biliary disease or index for suspicion of cholangitis is high
Provides both diagnosis and therapy via biliary decompression

Transabdominal ultrasound of abdomen / pelvis:
- Quick and accurate for detecting common bile duct (CBD) dilation is >90%

Question 40

How can you determine between acute cholecystitis and ascending cholangitis based off symptoms?

Answer 40

Acute cholecystitis
* A positive Murphy’s sign is predominantly seen in acute cholecystitis and diffuse RUQ pain in cholangitis
* Transabdominal ultrasound will show gallbladder wall thickening in acute cholecystitis
* LFTS normally normal

Question 41

Describe the initial management plan for ascending cholangitis

Answer 41

Broad-spectrum antibiotic therapy initially until antibiotic treatment can be guided with blood cultures:
- Piperacillin / tazobactam (or gentamicin + metronidazole in penicillin-allergic patients) with the aim to convert to oral antibiotics once biliary drainage has been achieved

Intravenous hydration

Correct electrolyte imbalances + coagulation abnormalities
* Fresh frozen plasma may be required for clotting abnormalities, especially in septic patients

Analgesia

Initiate the Sepsis 6 protocol if suspected within 1 hour

Question 42

Once you have provided initial mangement for ascending cholangitis - how do you treat biliary decompression? [1]

Answer 42

Biliary decompression (either non-operatively or through surgery)

Non-operative management
* ERCP ± sphincterotomy
* Insertion of biliary stent to allow drainage of bile
* Percutaneous trans-hepatic cholangiography (PTC) for those with stricture / malignancy or previous Roux-en-Y gastric bypass
* Nasobiliary drain

Surgical management
* Non-operative procedures are preferred due to the increased risks of surgery (bleeding, infection, abscess formation)
* Cholecystectomy ± common bile duct exploration
* Choledochotomy with T-tube placement

Question 44

Answer 44

Pneumothorax
Intestinal perforation resulting in pneumoperitneum
Subcutaneous emphysema
Pulmonary embolism
Acute respiratory distress syndrome

You can see the striations of pec major lateral to the right lung field. Pec major is only visible if there is subcut emphysema.