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Home , Biliary colic, Common bile duct stone

Aims and objectives

• Target audience: medical students in clinical years, and PAs

• Duration: 60 minutes

• Today: biliary , acute , and

• Pathophysiology, clinical features, investigations, management, prognosis • Multi-step SBAs: for a full understanding of the patient journey • Summary and Q&A

• Slides and previous recordings: app.bitemedicine.com

2

Case-based discussion: 1

History A 44-year-old Caucasian female presents to the emergency department with a 1-month history of intermittent right-sided abdominal pain, worse after eating a heavy meal.

On examination, the is soft and non-tender.

Observations HR 90, BP 128/89 mmHg, RR 16, SpO2 99%, Temp 37.2

6 Question Q1 Q2 Q3 Q4 Q5 Q6

What is the most likely diagnosis?

Cholecystitis

Common stone

Biliary colic

Cholangitis

Mirizzi syndrome

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Explanations Q1 Q2 Q3 Q4 Q5 Q6

What is the most likely diagnosis?

Cholecystitis Associated with RUQ pain and tenderness on examination, +ve Murphy’s sign and

Common bile duct stone Associated with obstructive symptoms (, dark urine, pale stools) or features of cholangitis

Biliary colic Intermittent RUQ pain after a heavy meal in a high-risk group, apyrexial with few/no examination findings

Cholangitis Associated with Charcot’s triad / Reynolds’ pentad

Mirizzi syndrome Common hepatic duct obstruction caused by extrinsic compression; usually presents with jaundice, fever, and RUQ pain

app.bitemedicine.com 9 Case-based discussion: 1

History A 44-year-old Caucasian female presents to the emergency department with a 1-month history of intermittent right-sided abdominal pain, worse after eating a heavy meal.

On examination, the abdomen is soft and non-tender.

Observations HR 90, BP 128/89 mmHg, RR 16, SpO2 99%, Temp 37.2

10 disease

(1) 11 Gallstone disease

Definitions (NICE CKS, 2019)

• A gallstone (cholelithiasis) is a solid deposit that forms within the

• Cholecystolithiasis describes in the gallbladder

• Choledocholithiasis describes gallstones in the

(2) 12 Question Q1 Q2 Q3 Q4 Q5 Q6

Which of the following is true regarding gallstones?

Mixed stones are the most common type of gallstone in the developed world

50% of gallstones are asymptomatic

Cholesterol stones mainly affect those with sickle cell disease

Anorexia is a risk factor for gallstones

Gallstones affect 20% of the general population

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Explanations Q1 Q2 Q3 Q4 Q5 Q6

Which of the following is true regarding gallstones?

Mixed stones are the most common type of gallstone in the developed worlds Cholesterol stones are the most common in the developed world

50% of gallstones are asymptomatic 80% gallstones are asymptomatic

Cholesterol stones mainly affect those with sickle cell disease Pigment stones mainly affect those with haemolytic disorders such as sickle cell disease

Anorexia is a risk factor for gallstones Although rapid weight loss and fasting are risk factors, a low BMI itself is not

Gallstones affect 20% of the general population Gallstone-related complications are the most common cause of GI admissions in Europe (EASL, 2016)

app.bitemedicine.com 15 Gallstones

Composition • Cholesterol: most common (80%) due to increased cholesterol, reduced bile salts and biliary stasis • Pigment: mainly affecting those with haemolytic disorders, or • Mixed

(3)

Cholesterol Mixed Pigment 16 Gallstones: pathophysiology

• 80% of those with gallstones are asymptomatic, often for years

Clinical features of gallstones

• Biliary colic: as the gallbladder contracts against a stone lodged in the

• Acute cholecystitis: inflammation of the gallbladder

• Ascending cholangitis: infection of the biliary tree, commonly due to CBD stone

17 Gallstone disease

Biliary colic • Gallbladder contracts against stone impacted in cystic duct • Constant RUQ pain after heavy meal • No fever or abdominal tenderness (NICE CKS)

(1) 18 Gallstone disease

Acute cholecystitis • Inflammation of the gallbladder

Calculous cholecystitis • Due to gallstone impacted at the neck of gallbladder or cystic duct à inflammation, bile stasis, bacterial overgrowth • RUQ tenderness, Murphy’s sign and fever

(1) 19 Gallstone disease

Acute cholecystitis • Inflammation of the gallbladder

Acalculous cholecystitis (5-10%) • Usually in severely unwell patients • Secondary to hypovolaemia, trauma, or systemic illness à gallbladder stasis and blockage of bile ducts • Poor prognosis

(1) 20 Gallstone disease

Ascending cholangitis • Infection of the biliary tree • Usually due to stone which has moved into the CBD • Obstruction à à infection (E. coli most common) • Other key causes: biliary strictures, cholangiocarcinoma, ERCP

(4) 21 Question Q1 Q2 Q3 Q4 Q5 Q6

Which of the following is a risk factor for gallstone disease?

Pregnancy

South Asian ethnicity

Male

Metformin use

Ulcerative

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Explanations Q1 Q2 Q3 Q4 Q5 Q6

Which of the following is a risk factor for gallstone disease?

Pregnancy Gallstones are more common due to reduced gallbladder motility and more cholesterol saturation of bile

South Asian ethnicity Caucasians are at high risk, as are Hispanic and Native-American ethnicities (NICE CKS, 2019)

Male Females are 2-3x more likely to develop gallstones (NICE CKS, 2019)

Metformin use Although diabetes is a risk factor, Metformin use is not associated with gallstone disease

Ulcerative colitis Crohn’s disease cause bile acid due to a terminal ileal disease à cholesterol supersaturated bile

app.bitemedicine.com 24 Introduction to gallstone disease

Epidemiology

• Gallstones affect 10-20% of the general population (NICE CKS, 2019)

• Gallstone-related complications are the most common cause of GI admissions in Europe (EASL, 2016)

‘4 F’s’: classic risk factors Female 2-3x more likely to develop gallstones

Fat BMI >30 is a key risk factor

Forties Risk increases significant from 40 years old Fertile Pregnancy is an important risk factor

25 Introduction to gallstone disease

Other risk factors (NICE CKS, 2019)

• Family history: particularly if first-degree relative

• Rapid weight loss/prolonged fasting: if exceeding 1.5kg/week, e.g. bariatric surgery

• Diabetes mellitus and NAFLD

• Crohn’s disease: due to a terminal ileal disease à cholesterol supersaturated bile

• Medication: COCP, HRT, octreotride, GLP-1 analogues, ceftriaxone

• Haemolytic conditions: e.g. sickle cell disease à pigment stones

26 Gallstone disease: clinical features (NICE CKS, 2019)

Biliary colic

Constant, steady RUQ or epigastric pain (not colicky)

Severe abdominal pain >30 minutes, but <8hours, often worse after fatty meal

Nausea and/or vomiting

No fever and no abdominal tenderness

27 Case-based discussion: 2

History A 56-year-old Caucasian male presents to the emergency department with a 4-hour history of RUQ pain and fever.

On examination, he is tender in the right upper quadrant and palpating the RUQ whilst the patient breathes in deeply causes significant pain.

Observations HR 110, BP 119/88 mmHg, RR 17, SpO2 98%, Temp 38.9

28 Gallstone disease: clinical features (NICE CKS, 2019)

Biliary colic Acute cholecystitis

Constant, steady RUQ or Features similar to biliary epigastric pain (not colicky) colic

Severe abdominal pain >30 Referred right shoulder tip minutes, but <8hours, often pain worse after fatty meal

Nausea and/or vomiting Fever, tenderness in RUQ

No fever and no abdominal Murphy’s sign positive tenderness

29 Gallstone disease: clinical features (NICE CKS, 2019)

Biliary colic Acute cholecystitis Ascending cholangitis

Constant, steady RUQ or Features similar to biliary Charcot’s triad: fever (often epigastric pain (not colicky) colic with rigors), jaundice, and RUQ pain Severe abdominal pain >30 Referred right shoulder tip Reynolds’ pentad: Charcot’s minutes, but <8hours, often pain triad + shock + altered mental worse after fatty meal status

Nausea and/or vomiting Fever, tenderness in RUQ Obstructive features: e.g. pale stools/dark urine No fever and no abdominal Murphy’s sign positive tenderness

30 Question Q1 Q2 Q3 Q4 Q5 Q6

Which of the following conditions is associated with a raised serum conjugated ?

Cholecystitis

Biliary colic

Cystic duct stone

Ascending cholangitis

Vesicoureteric junction stone

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Explanations Q1 Q2 Q3 Q4 Q5 Q6

Which of the following conditions is associated with a raised serum conjugated bilirubin?

Cholecystitis Bilirubin levels should be normal and patients should not be jaundiced

Biliary colic Bilirubin levels should be normal and patients should not be jaundiced

Cystic duct stone Usually results in biliary colic or cholecystitis, bilirubin levels should be normal

Ascending cholangitis Most commonly due to CBD stone, resulting in obstructive jaundice (conjugated hyperbilirubinaemia)

Vesicoureteric junction stone This is a type of renal stone, not gallstone

app.bitemedicine.com 33 Investigations: biliary colic

Primary investigations • Abdominal ultrasound: the first-line imaging investigation of choice to identify gallstones • : to identify evidence of biliary obstruction (raised ALP, bilirubin)

(5)

NICE CKS. Gallstone disease. (2019) and NICE (2014) 34 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: biliary colic

Primary investigations • Abdominal ultrasound: the first-line imaging investigation of choice to identify gallstones • Liver function tests: to identify evidence of biliary obstruction (raised ALP, bilirubin)

Investigations to consider • MRCP: if no common bile duct stones are seen on abdominal USS, but: • The CBD is dilated on abdominal ultrasound AND/OR • Liver function tests are abnormal (i.e. CBD stones are suspected)

• Endoscopic ultrasound (EUS): if MRCP does not allow a diagnosis to be made

NICE CKS. Gallstone disease. (2019) and NICE (2014) 35 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: cholecystitis

Primary investigations • FBC: leukocytosis with neutrophilia • Liver function tests: usually normal unless complications, e.g. obstructing CBD stone/cholangitis • U&Es: assess for electrolyte dysfunction / acute kidney injury • Coagulation profile: assess liver synthetic function, and required before procedures • VBG: assess for degree of lactic acidosis • Abdominal ultrasound: first-line imaging modality • Positive Murphy’s sign on palpation with the probe • Thickened gallbladder wall (≥3mm) • Distended gallbladder with the presence of gallstones • Pericholecystic fluid

(6)

NICE CKS. Gallstone disease. (2019) and NICE (2014) 36 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: cholecystitis

Investigations to consider • CT abdomen: if ultrasound is inconclusive • Traditionally considered less sensitive than ultrasound • Useful to assess for alternative pathology

(7) NICE CKS. Gallstone disease. (2019) and NICE (2014) 37 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: cholecystitis

Investigations to consider • CT abdomen: if ultrasound is inconclusive • Traditionally considered less sensitive than ultrasound • Useful to assess for alternative pathology

• MRCP: if no common bile duct stones are seen on abdominal USS, but: • The CBD is dilated on abdominal ultrasound AND/OR • Liver function tests are abnormal (i.e. CBD stones are suspected)

• Cholescintigraphy (HIDA) scan: not commonly performed, but consider if ultrasound is inconclusive • Technetium-labelled HIDA is taken up by hepatocytes à excreted into bile • Cholecystitis is associated with cystic duct obstruction = gallbladder will not be visualised

NICE CKS. Gallstone disease. (2019) and NICE (2014) 38 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: cholecystitis

(7B) 39 Case-based discussion: 3

History A 62-year-old Hispanic female presents to the emergency department with a 2-hour history of RUQ pain and fever.

On examination, she is tender in the RUQ and yellowing of her conjunctiva is noted. She also looks uncomfortable and is itching herself.

Observations HR 125, BP 109/75 mmHg, RR 19, SpO2 98%, Temp 39.4

40 Question Q1 Q2 Q3 Q4 Q5 Q6

What is the most likely underlying cause of this patient’s presentation?

Common hepatic duct stone

Common bile duct stone

Right hepatic duct stone

Cystic duct stone

Pancreatic duct stone

app.bitemedicine.com 41

Explanations Q1 Q2 Q3 Q4 Q5 Q6

What is the most likely underlying cause of this patient’s presentation?

Common hepatic duct stone Gallstones are formed in the gallbladder; the common hepatic duct is proximal to this

Common bile duct stone CBD stone à obstruction à cholestasis à infection of the biliary tree = ascending cholangitis

Right hepatic duct stone Gallstones are formed in the gallbladder; the right hepatic duct is proximal to this

Cystic duct stone This is the most common cause of cholecystitis, not ascending cholangitis

Pancreatic duct stone This would usually result in gallstone

app.bitemedicine.com 43 Investigations: ascending cholangitis

Primary investigations • FBC: leukocytosis with neutrophilia • Liver function tests: obstructive jaundice with raised ALP > ALT, and raised conjugated bilirubin • U&Es: assess for electrolyte dysfunction / acute kidney injury • Coagulation profile: assess liver synthetic function, and required before procedures • VBG: assess for degree of lactic acidosis • Blood cultures: ideally taken before commencing IV antibiotics • Abdominal ultrasound: first-line imaging modality to detect CBD dilatation and presence of gallstones

NICE CKS. Gallstone disease. (2019) and NICE (2014) 44 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: ascending cholangitis

Investigations to consider • CT abdomen: if ultrasound is negative; useful to exclude alternative pathology

• MRCP: gold-standard for diagnosis and used for pre-intervention planning

(8)

NICE CKS. Gallstone disease. (2019) and NICE (2014) 45 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Investigations: ascending cholangitis

Investigations to consider • ERCP: endoscopic investigation and intervention to remove stone(s) from CBD • MRCP usually required prior to ERCP

NICE CKS. Gallstone disease. (2019) and NICE (2014) 46 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Management: biliary colic

Management • Mild-to-moderate pain: offer an oral NSAID (e.g. ) or paracetamol whilst awaiting • Severe pain: offer IM diclofenac or IM (e.g. morphine) if required • Elective laparoscopic cholecystectomy: refer all people diagnosed with symptomatic gallstone disease • Lifestyle changes: avoidance of fatty foods and increasing fibre intake may help

NICE CKS. Gallstone disease. (2019) and NICE (2014) 47 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Question Q1 Q2 Q3 Q4 Q5 Q6

According to NICE, what is the advised surgical management of a patient diagnosed with cholecystitis?

Laparoscopic cholecystectomy within 6 weeks

Laparoscopic cholecystectomy within 2 weeks

Laparoscopic cholecystectomy within 72 hours

Laparoscopic cholecystectomy within 1 week

Open cholecystectomy within 72 hours

app.bitemedicine.com 48

Explanations Q1 Q2 Q3 Q4 Q5 Q6

According to NICE, what is the advised surgical management of a patient diagnosed with cholecystitis?

Laparoscopic cholecystectomy within 6 weeks This was previously advocated but has now been found to be associated with worse outcomes

Laparoscopic cholecystectomy within 2 weeks Should be performed within 1 week, not 2 weeks

Laparoscopic cholecystectomy within 72 hours Although most patients are operated on within 72 hours, guidelines state within 1 week of diagnosis

Laparoscopic cholecystectomy within 1 week Early cholecystectomy is advocated within 1 week of diagnosis (NICE, 2014)

Open cholecystectomy within 72 hours A laparoscopic approach is preferred and should be performed within 1 week of diagnosis

app.bitemedicine.com NICE. Gallstone disease: diagnosis and management (2014) 50 Management: cholecystitis

First-line management • IV fluids and analgesia • IV antibiotics: broad-spectrum required, e.g. cefuroxime and metronidazole • Early laparoscopic cholecystectomy • Perform within 1 week of diagnosis, but often performed within 72 hours (‘hot gallbladder’) • Delayed procedure (> 6 weeks from admission) was previously advocated • Early cholecystectomy: lower complications, shorter hospital stay, improved quality of life

Second-line management • Urgent cholecystostomy • Perform if early cholecystectomy is inappropriate due to sepsis/gangrene/perforation • Insertion of percutaneous cholecystostomy tube, with a delayed elective cholecystectomy 2-3 months after admission

NICE CKS. Gallstone disease. (2019) and NICE (2014) 51 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Management: ascending cholangitis

Initial therapy • IV antibiotics: broad-spectrum required, e.g. cefuroxime and metronidazole • IV fluids: patients are often septic and require aggressive rehydration

Bile duct clearance / biliary decompression options • ERCP: first-line procedure usually performed within 24-48 hours • Perform before or at the time of laparoscopic cholecystectomy • Endoscopic exploration of the with the removal of gallstones to facilitate drainage • Sphincterotomy may be performed to reduce the risk of future blockage

NICE CKS. Gallstone disease. (2019) and NICE (2014) 52 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Management: ascending cholangitis

(9) (10)

53 Management: ascending cholangitis

Bile duct clearance / biliary decompression options • Percutaneous trans-hepatic (PTC): if ERCP fails, PTC is an alternative measure (temporary measure)

(11) • Surgical drainage: performed if minimally invasive techniques above are not possible • Involves a choledochotomy (incision into the CBD) and T-tube insertion OR • Laparoscopic cholecystectomy with bile duct exploration

NICE CKS. Gallstone disease. (2019) and NICE (2014) 54 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Management: ascending cholangitis

Elective laparoscopic cholecystectomy • Performed following successful biliary clearance/decompression to reduce future gallstone-related complications

NICE CKS. Gallstone disease. (2019). 55 EASL. Clinical Practice Guidelines on the Diagnosis and Treatment of Gallstones (2016). Top-decile question

56

Top-Decile Q1 Q2 Q3 Q4 Q5 Q6 Q7 Question Explanations Whilst on ward round, your consultant points out a patient with Bouveret's syndrome. She asks you to describe the condition. What is your explanation?

An impacted stone in the cystic duct → common hepatic duct obstruction This is the basic description of Mirizzi syndrome

A gallstone enters the small bowel via cholecystoenteric fistula → small This is the basic description of gallstone

A gallstone erodes through the gallbladder → duodenal obstruction Passage of a large gall bladder stone through a bilio-duodenal fistula à gastric outlet obstruction

Duodenal tuberculosis → gastric outlet obstruction This is a recognized condition, but is not associated with a specific ‘syndrome’

Autosomal dominant → chronic + congenital heart disease This is the basic description of Alagille syndrome

app.bitemedicine.com NICE. Gallstone disease: diagnosis and management (2014) 58

Complications of gallstone disease

Complication Explanation

• Cholecystitis Inflammation of the gallbladder, usually due to cystic duct stone

• Ascending cholangitis Infection of the biliary tree, usually due to stone that has migrated to the CBD • Obstructive jaundice Due to a stone in the CBD; pale stools, dark urine

• Gallstones are the most common cause • Gallbladder empyema Uncommon complication of cholecystitis

• Rare form of small bowel obstruction due to impaction of a gallstone within the lumen of the via a cholecysto-duodenal fistula • Gallbladder cancer Gallstones increase risk by up to 5-fold (no established causation yet) • Mirizzi syndrome Common hepatic duct obstruction due to external compression from an impacted stone in the cystic duct or infundibulum of the gallbladder 60 Aims and objectives

• Target audience: medical students in clinical years, and PAs

• Duration: 60 minutes

• Today: biliary colic, acute cholecystitis, and cholangitis

• Pathophysiology, clinical features, investigations, management, prognosis • Multi-step SBAs: for a full understanding of the patient journey • Summary and Q&A

• Slides and previous recordings: app.bitemedicine.com

61 Further information

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62 References

1) BruceBlaus. Creative Commons Attribution-Share Alike 4.0 International license. https://en.wikipedia.org/wiki/File:Gallbladder_(organ).png 2) Alex Khimich / Public domain. https://commons.wikimedia.org/wiki/File:Gallstones.JPG 3) https://www.scientificanimations.com/ / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0). https://commons.wikimedia.org/wiki/File:Types_of_Gallstones.jpg 4) BruceBlaus / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0). https://commons.wikimedia.org/wiki/File:Gallstones.png 5) Mikael Häggström, M.D. - Author info - Reusing imagesWritten informed consent was obtained from the individual, including online publication. / CC0. https://commons.wikimedia.org/wiki/File:Ultrasonography_of_sludge_and_gallstones,_annotated.jpg 6) James Heilman, MD / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0). https://commons.wikimedia.org/wiki/File:Gallstones.PNG 7) James Heilman, MD / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0). https://commons.wikimedia.org/wiki/File:AcuteCholMark.png 7B) Myohan at en.wikipedia / CC BY (https://creativecommons.org/licenses/by/3.0). https://commons.wikimedia.org/wiki/File:HIDA.jpg 8) Hellerhoff / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0), https://commons.wikimedia.org/wiki/File:MRCP_Choledocholithiasis.jpg 9) Drus1a / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0). https://commons.wikimedia.org/wiki/File:ERCP.png 10) Samir (The Scope) at English Wikipedia / CC BY (https://creativecommons.org/licenses/by/2.5). https://commons.wikimedia.org/wiki/File:Pigment_stone_extraction.png 11) J. Guntau at German Wikipedia / Public domain. https://commons.wikimedia.org/wiki/File:Perkutan_transhepatische_Cholangiographie.jpg

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