GALL BLADDER DISEASES
Normal Features
- single layer of columnar cells
*Cholelithiasis (Gall Stones in GB)
- hardening of the contents of bile into crystals
- affect 5-10% of total population
- of these 80% are asymptomatic
Bile Duct Disorders
Choledocholithiasis
- blockage of the biliary
duct by Gall Stones
Biliary Congenital Disorders
Biliary Atresia
- common bile duct between the liver
and duodenum is blocked or absent - very rare
Signs ans Symptoms
- initially indistinguishable from neonatal jaundice
- jaundice
- clay coloured stools
- dark urine
- swollen abdomen
Choledocholithiasis Proximal to
Hepatopancreatic Ampulla
- blockage of the bile ducts
Cholecystitis
- inflammation of the GB
- Adema and pressure build up in GB
--> risk of perforation and peritonitis
Acute
- 5-10% will have cholecystectomy
(GB removed)
Chronic
- does NOT require acute cholecystitis
- does NOT require duct obstruction
Signs and Symptoms
- RUQ pain
- irregular attacks after eating,
especially fatty foods
Histology
- Rokitansky-Aschoff Sinuses
- thickened GB wall
- fibrotic changes to the mucosa
due to chronic inflammation
Rokitansky-Aschoff Sinuses
- diverticula of the mucosa of the GB
Cholangitis
- infection of the GB by pathogens (bacteria or parasites)
--> usually Gram (-) bacteria - usually secondary to cholecystitis
Choledocholithiasis Within
Hepatopancreatic Ampulla
- blockage of the bile ducts
Pancreatitis
- 2 main causes of acute pancreatitis
1 = choledocholithiasis
2 = alcoholism (unknown method)
Gram (-) Bacteria
Clostridium
Bacteroides
Lactose fermenting
Klebsiella
Escherichia Choli
enterobacter
Signs and Symptoms
- fever
- chills
- URQ abdominal pain
- jaundice
Complications
- ascending cholangitis
--> infection ascends up to the liver - sepsis
*Carcinoma of the GB
- starts with Porcelin GB
Pathophys.
- usually adenomcarcinoma
--> since glandular cells
Risk Factors
- Gall Stones present 60-90%
- 70% female
--> recall that females more common
than men for Gall stones
Prognosis
- 1% survival for 5 years
--> GB is non-essential visceral organ
--> not diagnosed until
metastasized to essential organ
Cirrhosis Causing
Auto-Immune
Bile Duct Disorders
Primary Sclerosing Cholangitis (PSC)
Risk Factors
- 2M : F
--> only auto-immune liver disease more common in men - 30-50 yrs old
- 70% have background of Ulcerative Colitis (sometimes CD)
Causes and Defining Features
- progressive inflammatory destruction of post-hepatic biliary tree (ducts)
- Primary SCLEROSING
--> primarily causes sclerosis (scarring) of the entire biliary tree
--> sclerosis is very general widespread auto-immune
--> IBD background also
Primary Biliary Cholangitis (PBC)
Risk Factors
- more common in women than men
- NO association with IBD
Causes and Defining Features
- cholangiohepatitis = slow, progressive destruction of the small bile ducts of the liver by immune cells
- PRIMARY BILIARY
--> antibodies attack primary start of biliary tree
--> caniculi of hepatocytes - PRIMARY BILIARY
--> very specific and primary to biliary tree only
--> no background of IBD like in Primary SCLEROSING cholangitis - results in cholestasis = causing bile and other toxins to build up in the liver
- +/- granulomas
Defining Serum Tests
- high IgM antibodies
- high anti-mitochondrial antibodies
- high alkaline phosphatase
*Terminology
- Chole = means GB --> think the "whole GB"
- lithi = means stone --> think "little stone"
- cyst = refers to the cystic duct --> the main duct to the Gb
- docho + lithiasis = means little stone in "common duct" = "docho"
- gitis = means bacterial infection
--> think of a stone starting in the GB and
--> moving down the biliar tree (cystic duct then common duct)
--> infection that ascends
Cholelithiasis (1/3 triad)
- Gall stones in the GB
- colicky RUQ pain that goes on and off
- worse when eating fatty foods since the GB is contracting
Cholecystitis (2/3 triad)
- Gall stones in the cystic duct
- CONSTANT - not colicky or transient pain
- positive Murphy's sign
--> patient breathes in
--> liver and GB become exposed under rib cage
--> RUQ pain when you push in there - fever since inflammation
--> note there is no Jaundice in cholecystitis since the common bile duct is not blocked
Choledocholithiasis (2/3 triad)
- Gall stones in the common bile duct
- the duct is larger so there is less inflammation than in cholecystitis
--> less fever - But the common bile duct is obstructed so there is bilirubin back up
--> jaundice
Cholangitis (AKA ascending Cholangitis) (3/3 triad)
- Choledocholithiasis that has lead to infection and inflammation of the entire biliary tree above
- Charcot's triad of symptoms
--> RUQ pain, fever, jaundice
--> think of Charcot's triad as the sum of the previous three main symptoms - Note Charcot's Triad can move into Reynold's Pentad if not treated
Reynold's pentad
--> Charcot's + hypotension and altered mental status
--> moving into realm of shock
GB Anatomy and Physiology
Summary of Outcomes of Cholithiasis
Choledocholithiasis
- Gall stone in the bile duct tree
- can lead to cholcystitis (short term) or cholangitis
- can lead to cholangitis (long term)
Cholecystitis
- inflammation of the GB
- Adema and pressure build up in GB
--> risk of perforation and peritonitis
Chronic
- does NOT require acute cholecystitis
- does NOT require duct obstruction
Histology
- Rokitansky-Aschoff Sinuses in GB
- thickened GB wall
- fibrotic changes to the mucosa
due to chronic inflammation
Rokitansky-Aschoff Sinuses
- diverticula of the mucosa of the GB
Signs and Symptoms
- RUQ pain
- irregular attacks after eating,
especially fatty foods
Acute
- 5-10% will have cholecystectomy
(GB removed)
Rare Obstruction
- Gallstone Illeus
- Gallstone gets through fistula
to obstruct the illeum
80% Assymptomatic
- do nothing
Risk Factors
- 5 Fs
Fat
Fertile
(hormones increase cholesterol synthesis
and excretion through bile ducts)
Female
Fair
(caucasion)
> Forty
Signs and Symptoms
- Biliary Colic
- nausea
- vomiting (emesis)
- fever
- jaundice
--> if the biliary tree is obstructed
Biliary Colic
- RUQ abdominal pain
- since by the liver and diaphragm
--> c3,c4,c5
--> radiates to right neck, shoulder, jaw - constant pain
--> lasts between 15 min. --> 4 hrs. - usually due to stone in cystic duct
Causes
- hypomotility of the GB
- imbalance of bile salts and cholesterol
- loss of acidity of bile in the GB
--> allows the Ca2+ to crystallize
Terminology
- Chole = means GB --> think the "whole GB"
- lithi = means stone --> think "little stone"
- cyst = refers to the cystic duct --> the main duct to the Gb
- docho + lithiasis = means little stone in "common duct" = "docho"
- gitis = means bacterial infection
--> think of a stone starting in the GB and
--> moving down the biliar tree (cystic duct then common duct)
--> infection that ascends
Cholangitis (AKA ascending Cholangitis) (3/3 triad)
- Choledocholithiasis that has lead to infection and inflammation of the entire biliary tree above
- Charcot's triad of symptoms
--> RUQ pain, fever, jaundice
--> think of Charcot's triad as the sum of the previous three main symptoms - Note Charcot's Triad can move into Reynold's Pentad if not treated
Reynold's pentad
--> Charcot's + hypotension and altered mental status
--> moving into realm of shock
Choledocholithiasis (2/3 triad)
- Gall stones in the common bile duct
- the duct is larger so there is less inflammation than in cholecystitis
--> less fever - But the common bile duct is obstructed so there is bilirubin back up
--> jaundice
Cholecystitis (2/3 triad)
- Gall stones in the cystic duct
- CONSTANT - not colicky or transient pain
- positive Murphy's sign
--> patient breathes in
--> liver and GB become exposed under rib cage
--> RUQ pain when you push in there - fever since inflammation
--> note there is no Jaundice in cholecystitis since the common bile duct is not blocked
*Cholelithiasis (1/3 triad)
- Gall stones in the GB
- colicky RUQ pain that goes on and off
- worse when eating fatty foods since the GB is contracting
- affect 5-10% of total population (mostly women 5 Fs)
- of these 80% are asymptomatic
3 types of Gallstones
Treatment for Cholelithiasis +/- others
- based on symptoms vs. non symptoms
- no symptoms = watch and wait
- symptoms with Gallstones present
--> transabdominal ultrasound
--> MRCP
--> ERCP
MRCP
- magnetic resonance Cholopancreatography
ERCP
- endoscopic retrograde Cholopancreatography
Notes:
- ERCP for cholelithiasis and possible obstriction is both diagnostic and treatment tool
--> may remove the Gallstone = cholithiectomy, stent biliary tree, or cholecystectomy
80-85% Mixed
- high inorganic calcium salts
--> calcium carbonate, calcium phosphate and calcium palmitate
--> radiographically visible on X-ray - Commonly secondary to infection of the biliary tract
5-10% Pure Pigmented
- SOFT small and black
- > 90% unconjugated bilirubin
- hemolysis or bacterial infection
- glucuronidase reversing the process and unconjugating the bilirubin
--> ALL these increase unconjugated UCB
--> think this is unconjugated so thus can bind with Calcium
--> so it makes a Calcium Bilirubin salt which is brown or black = darker = Pigmented
10% Pure *Cholesterol
- HARD + light yellow --> green --> brown
- +/- dark, central spot
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
Heme Metabolism and Bilirubin
Conjugation of *Bilirubin
- UDP-glucorondyl - transferase
--> conjugates bilirubin - beta-glucuronidase
--> reverse the reaction and removes a glucuronic acid group
Notes:
- Note that Heme must go through 2 processes before broken into bilirubin
- Heme --> biliverdin
- done by Heme oxygenase
- biliverdin --> bilirubin
- done by biliverdin reductase
Clinical Cases
Clinical Case
Clinical Case
Notes:
- note that
PAthophys of Cholesterol Gallstones
- high cholesterol to bile salt ratio in the GB
Fibrates Increase Cholesterol Gall Stones
- Fibrate main action = increase Lipoprotein lipase
--> increases the releasing of lipids from LDLs and Chylomicrons
--> stores FFAs and lipids to remove them from the blood and causing damage - secondary Fibrate action = inhibits cholesterol - hydroxylase enzyme
--> lowers bile acid production - fibrates are perfect storm for cholesterol gall stones
--> increases FFAs and lipid storage (including cholesterol in t he GB)
--> decreases the bile salts production (chol hydroxylase) that are needed to trap the cholesterol in micelles in the GB
*Porcelain GB
- starts with Porcelin GB and leads to adenocarcinoma of the GB
*Porcelain GB on CT scan
- shows calcification and thickenning of the GB
*Cholestasis (GB - not supplying bile salts)
- classic presentation = fatigue, pruritis (nonspecific to any rash), hepatomegaly, raised Alk Phosph
Rare Gallstone Complications
- Gallstone Illeus
Gallstone *Illeus
- usually there has to be an abnormal connection between the GB and the small intestine for a large stone to enter the intestines
- can present as a mix of SBO and appendicitis
- see air in the GB and the stomach
Diagnosis of Cholecystitis
- transabdominal ultrasound is the gold standard
- when this not available, use radiotracer GB scan
- if the die goes past the GB and it is not seen, this means just the cystic duct is blocked
5 Fs of GB stones
- ntoe these mostly come in women from 2 things
--> pregnancy
--> OCPs
*Pregnancy and GB stones
- estrogen
--> increases the amount of cholesterol made in pregnant women- progesterone
--> decreases GB motility
- progesterone
- Brown = Bacteria
--> from the excess glucoronidase
--> bacteria are able to reverse the bilirubin glucoronidation
--> bac to Unconjugated UCB - Black = SCD
--> excess pre hepatic unconjugated UCB