Diseases of the Gallbladder
1. Cholelithiasis (Stones in the gallbladder)
2. Acute Cholecystitis (Inflammation from stones obstruction and Injury > Infection)
3. Acalculous Cholecystitis (Idiopathic, often associated with severe diseases and Ischemia)
4. Choledocholithiasis (Stones obstructing bile duct)
5. Cholangitis (Inflammation of the duct due to Obstruction, Life threatening, Bacteria Overgrowth)
6. Carcinoma of gallbladder (Chronic Obstruction and Cholecystitis, Porcelain gallbladder)
7. Primary Sclerosing cholangitis (Hardening and Narrowing of the duct, Idiopathic)
8. Primary Biliary Cirrhosis (Autoimmune disease of the duct causing cirrhosis)
9.
Cholangiocarcinoma (Carcer of the Bile duct)
10. Choledochal cysts (Usually Congenital cysts of the biliary tract)
11. Bile Duct Strictures (Abnormal narrowing due to different causes)
12. Biliary Dyskinesia (Sphincter of Oddi dysfunction)

Note
- In Diagnosis
US is often used for Gallbladder diseases
Cholangiography (also in mgt) is often used for Biliary duct disease/Obstruction
CT is used to confirm complications such as abscess and perforation
Biopsy is confirmatory in cirrhosis and cancer
- As a rule, Dx and Tx go from less invasive and easy to perform to more complicated as long as they are effective
- Every disease of the tract affects both Extrahepatic and Intrahepatic duct except Primary Biliary Cirrhosis (Autoimmune PBC)

Cholelithiasis
Cholelithiasis refers to Stones in gallbladder
3 types
1. Cholesterol stones
- Yellow/Green in colour
- Associated with Hypercholesterolemia.
2. Pigment stones
- Black or Brown stones
- Black is associated with Xcess bilirubin of any cause and alcoholic cirrhosis
- Brown takes the colour of bilirubin (brown) because bilirubin is already secreted, gets obstructed and solidifies to brown stones.
3. Mixed stones
- cholesterol and pigment stones (Black and/or Brown)
- Accounts for majority of stones (Some formed from obstruction (brown), some formed from xcess xterol)

Cholesterol stones
Associated with conditions with increased body cholesterol
1. Metabolic syndromes
2. Increased Exposure to Preg.
hormones
3. Ileal dysfnx
- In resection,
- In chrons disease - Crohns affecting ileum = ileum inflammation, ileum can't reabsorb bile salts = xterol cummulate,
Remember that bile salts are synthesized from cholesterol
4. Advanced age (correlation is due to increased body fat in older peeps = inc. xterol)
5. Native American ancestry
6. Cirrhosis
- Cholesterol stones develop due to dysfnx and obstruction of gallbladder,
- Also cholesterol stones develop due to poor synthesis of bile salts from xterol due to loss of liver fnx.
- Liver synthesizes bile salts.
7. Cystic Fibrosis 
due to clogging of duct with thick mucous)

Pigment stones
- Black stones  (Black often due to xcess bilirubin from xcess hemolysis)
- Often found in
1. Hemolysis
2. Alcoholic cirrhosis
Brown stones Drown in the Ducts
Brown stones
- found in Bile ducts
- due to Biliary tract infection
-- Leads to inflammation
-- Inflammed duct causes obstruction of bile = Accumulation = Brown stones

Clinical Presentation of Cholelithiasis
1. Assymptomatic (Often incidental finding)
2. Biliary colic
- Defined as sudden pain in Epigastric region (esp. RUQ) due to gallstone blocking cystic duct
- Also called Gallstone attack
- A cardinal symptom of gallstone
- Pain occurs after feeding when the gallbladder contracts against this obstruction.
- Biliary colic is also common at night
- Pain usually lasts for atmost a few hours
- Pain varies in severity
3. Boas sign
- Pain of Biliary Colic referred to Right Subscapular region
- Remember Boas sign as a pain snake extending from the RUQ region to the subscapular region
 
Complications of Cholelithiasis
Think of
- Stones causing injury (hence inflammation)
- Stones passing out to block the duct
- Stones passing out to block the ileum (ileus) 
1. Cholecystitis (Acute or Chronic)
- Inflammation of the cyst
- Could be due to the stones causing inflammation due to chronic injuries to gallbladder wall during contraction.
- Also Stones causing obst may lead to stasis and overgrowth of bacteria = Inflammation
2. Choledocholithiasis
- means stones in the Bile duct
- occurs coz d gallbladder forces a stone out, but the stone gets stuck in the duct
3. Gallstone ileus
- Stone successfully passes through the duct but gets stuck in the ileum
- could also be as a result of fistula between the Gallblader and the intestine
4. Malignancy
- as a result of chronic inflammation and repair.

Diagnosing Cholelithiasis
1.
RUQ ultrasound (preferred)
- High Sensitivity and Spec for stones > 2mm
- Cheaper and easily achievable
2. CT scans and MRI

Treatment for cholelithiasis
1. Elective cholecystectomy
- only for symptomatic pts

Acute Cholecystitis
- Acute inflammation of the gallbladder due to injuries from gallstones and obstr of the cystic duct.
- Recurrent acute cholecystitis can lead to Chronic cholecystitis

Symptoms of Acute cholecystitis
1. Pain
- Pain may last several days vs Biliary colic lasting few hours
- localized to RUQ and Epigastrium
- May also see Boas sign
2. N/V (Due to gastric irritation)
3. Anorexia/Loss of Appetite

Signs
Acute Cholecystitis is inflammation
Expect to see the signs of inflammation, such as Pain, Inc. WBC, fever etc
1. RUQ tenderness/rebound tenderness
2. Murphy sign (Not always present)
- described as inspiratory arrest on deep palpation of RUQ
- Pathognomonic
3. Hypoactive bowel sounds
4. Fever (Low grade)
5. Leukocytosis

Diagnosis of Acute Cholecystitis (HIDA scan)
1. RUQ US
- Test of choice coz its cheap, Non-invasive and convenient.
- High Sens and Specs
- Thickened gallbladder wall
- Pericholecystic fluid (Fluid around the gallbladder)
- Distended gall bladder
- Stones in gall bladder
2. CT
Use if you suspect complicatns
- Perforation
- Abscess
- Pancreatitis (Seems CT is more sensitive for use in Pancrease vs US for Gall bladder)
3. HIDA scan
- As good as US
- Use if US is inconclusive
- Rules out Acute cholecystitis
- attempt to visualize Gallbladder 4 hrs after inject

Treatment of Acute Cholecystitis
1. Admit pt because pt is very sick
2. Conservative Mgt
- Prevent further injury with Fasting
- IV fluids (For hydration and compenstae for fasting)
- IV antibiotics for infection
- Analgesic for pain
- Correct electrolyte abnormalities
3.
Surgery
- Preferred Early (24-48hrs) cholecystectomy for symptomatic.
- High recurrence if no surgery is done

Acalculous cholecystitis
- No stones obstructing the gallbladder or duct
- approx 10% of acute cholecyttitis
- Idiopathic
- Seen in
1. Severe underlying illness
2. Dehydration
3. Ischemia
4. Burns
5. Severe trauma
6. Postoperative state.
- Treatment 
1. Emergent Cholecystectomy (Choice)
2. Percutaneous drainage with Cholecystostomy for very ill pts

Choledocholithiasis
Refers to stones in the common bile duct (CBD)
1. Primary choledocholithiasis
- Stones develop in the CBD
2. Second choledocholithiasis (Most common)
- Stones dev. in the gall bladder but gets stuck in the common bile duct
Symptoms of Choledocholithiasis
General symptoms that indicate obstruction of the Gallbladder and duct
- RUQ Pain
- Jaundice
- Pruritus (due to accumulation of bile ducts in the blood secondary obstruction) 
 
Signs of Choledocholithiasis
Mostly signs of Biliary tract obstruction
Increased
1. ALP (not specific for gallbladder, may also indicate bone etiology)
2. Gamma-glutamyl transferase (GGT) (More specific for gallbladder disease)
3. Direct Bilirubin -
- Liver fnx properly, and indirect bilirubin is conjgated with glucoronide to become direct bilirubin.
- Direct bilirubin is then secreted in bile
- Due to obstructed, its accumulates in the serum
4. Jaundice
- Yellowing of skin and Mucous membranes
- Due to accumulation of bilirubin
Others
- Pruritus
- Clay colored stools (due to lack of bilirubin in bile brown pigment)
- Dark urine(From excess excretion of accumulated bilirubin in urine)

Diagnosing Choledocholithiasis
1. Initial study is RUQ US
2.
Signs of Obstruction and Biliary Tract disease
3. Cholangiography is the Gold standard
- ERCP is Gold standard (High Sens and Specs)
- PTC is alt

Treatment for Choledocholithiasis
- As a rule, Dx and Tx go from less invasive and easy to perform to more complicated as long as they are effective
1. ERCP with Sphincterotomy
2. Stone extraction with Stent placement
3. Laparoscopic choledocholithotomy

Cholangitis
Life threatening Inflammatory reaction from infection of Biliary tract
- Due to Obstruction of bile duct, Injury from stones and Biliary stasis and Bacteria overgrowth
- Obstruction = Biliary stasis = Overgrowth of bacteria = Infection and Inflammation

Causes of Cholangitis
- conditons that obstruct the bile duct and cause stasis
1. Choledocholithiasis (Stones obstructing the CBD)
2. Pancreatic and Biliary tumors cauisng obstruction
3. Postoperative strictures (From scarring) which occlude the duct
4. ERCP and PTC - these may cause acute inflammation and eventual scarring and occlusion
5.
Choledochal cysts (Cysts in the bile duct) causing obstruction and stasis.

Symptoms of Cholangitis
Genral symptoms of Gallbladder disease plus Systemic inflammatory reaction (Life threatening)
1. RUQ pain
2. Fever (due to immune activation)
3. Dizziness (Same mechanism as AMS)
4. Altered Mental capacity (Due to decreased cerebral perfusion from systemic vasodilation)
5. May show signs of AKI in severe cases

Signs
1. Charcot Triad
Signs of Gallbladder infection and Obstruction
- RUQ pain
- Jaundice
- Fever
2. Reynolds pentad
- Signs of Gallbladder disease and other systems affected (CNS and CardioVascular)
- RUQ pain
- Jaundice
- Fever
- Septic shock
- Altered Mental Stasus
Reynolds is Reypidly fatal

Diagnosing Cholangitis
1. RUQ US
2. Blood tests
- Hyperbiirubinemia
- WBCs
- Mild inc in Transaminases
3. Cholangiography
- Definitive tests
- Identifies cause
- Contraindicted in the acute phase of cholangitis (done after 48hrs of afebrile)
- PTC when duct is dilated
- ERCP when duct is normal

Treatment of Cholangitis
1. Admission
2. IV fluids
3. Blood cultures requested
4. IV antibiotics
5. Close monitoring of systems
- Decompress CBD through Cholangiography
Done after pt is afebrile for 48hrs or when pt wont respond to tx
1. PTC (Catheter drainage)
2. ERCP (Sphincterotomy)
3.
Laparotomy (T-tube insertion)

Gallbladder Carcinoma
- Adenocarcinomas
- Elderly
- Undetected until End stage
- Risk factors = Stones, Fistula and Porcelain
- Symptoms and Signs suggest Obstruction, gallbladder disease and malignancy
- Palpable gallbladder = Advanced disease
- Treatment
Surgical = Cholecystectomy/Radical
- Poor prognosis

Primary Sclerosing Cholangitis (Hardens the Ducts till they form beads)
- UC associated with PSC
- Idiopathic
- Chronic and progressive
- Idiopathic Inflammation = Scarring = Occlussion of ducts
- Affects any of the ff
1. Intrahepatic bile ducts
2. Extrahepatic bile ducts
3. Both
- Associated with Ulcerative Colitis (UC)

Signs and symptoms
- Insidious
- Signs and symptoms are those of duct obstruction due to Sclerosing of the bile duct
- Malaise, fatigue and weight loss are present in all also due to malabsorption.

Diagnosing of Primary Sclerosing Cholangitis
Cholangiography
- see multiple areas of bead-like stricturing and bead-like dilations of affected ducts.

Treatment for Primary Sclerosing Cholangitis 
Treatment is usually symptomatic
- Cholestyramine for itching
- Cholangiography to relieve obstruction
- Definitive  cure is liver transplant

Primary Biliary Cirrhosis (PBC)
- Autoimmune PBC
- A disease condition xterized by destrcution of Intrahepatic bile ducts. (Unlike PSC that involves Intrahepatic and Extrahepatic)
- Leads to cholestasis
- An autoimmune disease
- common in middle aged women

Signs and Symptoms of Primary Biliary Cirrhosis
- Are related to both Gallbladder obsr and Liver cirrhosis
1. Pruritus and Jaundice (From accumulaion of Bile salts and Bilirubin)
2. RUQ discomfort
3. Hypercholesterolemia
- inability due produce bile from xterol due to accumulation and progressive loss of liver fnx
4. Osteoporosis signs and symptoms
- Occurs because Liver cannot properly prd 25-HO vit D
5. Signs and Symptoms of Portal HTN
- due to destruction of perivascular live tissue

Diagnosing of PBC
1. Cholestatic LFTs
- ALP
- Gamma-glutamyl transferase (GGT)
2. +ve AMA
- Sensitive and Specific
- Rules out disease if -ve
- Hallmark
- Confirm with Liver biopsy
3. Elevated IgM
- because its an autoimmune disease
4. US or CT
- check for obstruction that may be relieved.

Treatment of PBC
1. Symptomatic
2. UDC acid for PBC
- Ursodeoxycholic acid
- Slows progression of disease
3. Definitive cure is Liver transplantation

Cholangiocarcinoma
A tumor of Intrahepatic or Extrahepatic bile duct
Common in old > 70
Affects 3 regions
1. Proximal third of Common Bile Duct (CBD)
-  Klatskin tumor
2.
Distal Extrahepatic
- Better resectability
3. Intrahepatic (Least Common)
Prognosis is poor

Risk factors
are diseases affecting the Intrahepatic/Extrahepatic ducts
- Primary Sclerosing Cholangitis (PSC)
- Choledocholithiasis (Stones in CBD)
- Choledocyts (Congenital cysts)
- Clonorchis Sinesis (Hong Kong)

Signs and Symptoms of Cholangiocarcinoma
- Are those of 
1. Obstruction - eg Pruritus, Jaundice
2. Malignancy - palpable mass
3. Malabsorption - Weight loss, Oily stools

Diagnosis of Cholangiocarcinoma
Same diagnosis for all Biliary tract disease
1. Cholangiography
- Detects unresectable tumours
 
Treatment of Cholangiocarcinoma
- Most common tumors (Klatskin)  are not resectable
- Mostly paliative
1. Cholangiography with stent placement to relieve obstruction

Choledochocysts
- Cystic dilation of the Biliary tree
- usually congenital
- common in women
- Causes pncreatitis
- involves the
1. Extrahepatic bile duct
2. Intrahepatic bile duct
3. Both

Complications
are those of prolonged obstruction, liver disease and malignancy
1. CholangioCA (Most feared, 20%)
2. Hepatic abscess
3. Pancreatitis
4. Cirrhosis

Diagnosing Choledochocysts
1. Ultra Sound (US) to detect obstruction
2. but remember Cholangiography is definitive for the ducts
3. CT is good for detecting complicatins like peforation, Abscess etc

Treatment for Choledochocysts 
- Complete resection of cyst
- Enterobiliary anastomoses to restore continuity of biliary system.

Bile Duct Stricture
Refers to narrowing of the the bile duct

Common cause is Iatrogenic (eg A surgery around the gallbladder/billiary tract)
Other causes include diseases causing obstruction and narrowing of the bile duct.
e.g Primary Sclerosing Cholangitis

Signs and Symptoms
Include those of Obstructed bile ducts and their complications

Common complications
1. Secondary Biliary Cirrhosis
2.
Liver abscess
3. Ascending cholangits

Treatment for Biliary Stricture
1. Endoscopic Retrograde CholangioPancreatography (ERCP) stenting
2. Surgical bypass if complete obstruction/ErCP fails

Biliary Dyskinesia
- Motor dysfunction of the Sphincter of Oddi
(Spincter of Oddi is the outlet of the CBD and Pancreatic duct
- Leads to episodes of Biliary Colic
- No evidence of gallstones on diagnostic studies

Symptoms
Biliary colic

Diagnosing Biliary Dyskinesia
1. Hepatobiliary IminoDi Acetic acid (HIDA) scan + Cholecystokinin (CCK)
(CCK contracts gallbladder as it relaxes the Sphincter of Oddi)

Treatment for Biliary Dyskinesia
- Open the sphincter or stop the pain and prevent complications 
1. Laparoscopic Cholecystectomy (Prevents colic/Complications)
2. ERCP sphincterectomy (creates a passage).

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