Biliary Atresia Flashcards
1
Q
What are the benign tumours of the gallbladder
A
Adenomas
Inflammatory polyps
Adenomyosis
2
Q
Benign epithelial tumours, representing localised neoplastic growth of the lining epithelium
A
Adenomas
3
Q
Classifications of adenomas
A
- Tubular
- Papillary
- Tubulo-Papillary
4
Q
Macroscopic picture of inflammatory polyps
A
Sessile mucosal projections
5
Q
Histology of inflammatory polyps
A
Infiltration of the stroma by chronic inflammatory cells & lipid-laden macrophages
6
Q
Morphology of adenomyosis
A
- Hyperplasia of the gallbladder’s muscle layer
- Presence of intramural hyperplastic glands
7
Q
Presence of stones within the bile ducts of the biliary tree
A
Choledocholithiasis
8
Q
Stones in Choledocholithiasis are usually
A
pigmented and associated with biliary tract infections
9
Q
Choledocholithiasis may be asymptomatic, or present with the following symptoms:
A
- Obstruction
- Pancreatitis
- Cholangitis
- Hepatic abscess
- Secondary biliary cirrhosis
- Acute calculus cholecystitis
10
Q
Bacterial infection of the bile ducts
A
Cholangitis
11
Q
Causes of Cholangitis
A
Any lesion that creates obstruction to bile flow:
- Most common: Choledocholithiasis and biliary strictures
- Less common: Indwelling stents or catheters, tumours, acute pancreatitis
12
Q
Pathogenesis of cholangitis
A
- Entry of bacteria into the biliary tract through the sphincter of Oddi
- Ascending cholangitis: Infection of intrahepatic biliary radicles
- Usually enteric gram-negative aerobes, such as E. coli, Klebsiella, Enterococcus or Enterobacter
13
Q
Clinical features of cholangitis
A
Fever, chills, abdominal pain, & jaundice
14
Q
Microscopic findings of cholangitis
A
- Acute inflammation of the wall of the bile ducts, with entry of neutrophils into the
luminal space - Suppurative Cholangitis: Most severe form of cholangitis, in which purulent bile fills
and distends bile ducts
15
Q
Progression & Complications of cholangitis
A
Suppurative Cholangitis → Sepsis
16
Q
Congenital dilations of the common bile duct
A
Choledochal cysts
17
Q
Epidemiology of choledochal cysts
A
Presentation in childhood (age<10yrs); Non-specific symptoms of jaundice and/or
recurrent abdominal pain
About 20% of cases: Symptomatic, only in adulthood
18
Q
Different morphological forms of choledochal cysts
A
- Segmental or cylindric dilation of the common bile duct
- Diverticuli of the extra-hepatic ducts
- Choledochoceles (cystic lesions that protrude into the duodenal lumen)
19
Q
Complications of choledochal cysts
A
Predisposition to stone formation, stenosis and stricture, pancreatitis, & obstructive biliary complications (intra-hepatic)
Elevated risk for the development of bile duct carcinoma (older patients)
20
Q
Complete or partial obstruction of the lumen of the extrahepatic biliary tree (within the first 3 months of life), characterised by progressive inflammation and fibrosis of intra- or extrahepatic bile ducts
A
Biliary atresia
21
Q
Epidemiology of biliary atresia
A
- One third of infants with neonatal cholestasis
- Most frequent cause of death from liver disease in early childhood
- 50% to 60% of children referred for liver transplantation
22
Q
Pathogenesis of biliary atresia
A
- Fetal form:
- Cause: Anomalous intrauterine development of the extrahepatic biliary tree
- Commonly, association with: i. Malrotation of abdominal viscera, ii. Interrupted
inferior vena cava, iii. Polysplenia, iv. Congenital heart disease - Perinatal form:
- Destruction of a normally appearing bill. tree, after birth
- Aetiology: Unknown; But, association with viral infection (Reovirus, Rotavirus,CMV) & autoimmunity
23
Q
Morphology of biliary atresia
A
- Inflammation and fibrosing stricture of the hepatic or common bile ducts
- Peri-ductular inflammation of intra-hepatic bile ducts, with destruction (1/3 of cases)
- Progressive destruction of the intra-hepatic biliary tree
- Extrahepatic biliary obstruction, manifested as bile ductular proliferation, portal tract oedema & fibrosis, & parenchymal cholestasis (2/3 of cases)
- Inflammatory destruction of intra-hepatic ducts
24
Q
Clinical features of biliary atresia
A
Infants with biliary atresia → Neonatal cholestasis:
- Normal birth weight
- Postnatal weight gain
- Normal stools (initially) → Acholic stools (with disease progression)
25
lab findings of biliary atresia
- Serum bilirubin values: 6-12 mg/dL
- Moderately elevated aminotransferase & alkaline phosphatase levels
26
Tx of biliary atresia
Liver transplantation with accompanying donor bile ducts
27
Stones in the Gallbladder
Cholelithiasis
28
Epidemiology of Cholelithiasis
- 10-20% of adult population
- >80%: “Silent”; individuals remain free of biliary pain or other complications for a long period of time
29
Types of Cholelithiasis
- ~90%: Cholesterol stones; containing more than 50% of crystaline cholesterol monohydrate
- 10%: Pigment stones; composed predominantly of bilirubin calcium salts
30
Risk factors for cholesterol stones
- Female gender
- Oral contraceptives and Pregnancy
- Obesity and metabolic syndromes
- Gallbladder stasis
- Hyperlipidaemia syndromes
31
Risk factors for pigment stones
Chronic haemolytic syndromes Infection of the biliary tree
Crohn disease
32
Clinical features of Cholelithiasis
Biliary pain: Constant or “colicky” (spasmodic)
33
Complications of Cholelithiasis
Cholecystitis and Empyema – Perforation – Fistulas – Inflammation of the biliary tree (Cholangitis)
Obstructive cholestasis – Pancreatitis
34
Condition characterized by inflammation & obliterative fibrosis of intra-hepatic & extra-hepatic bile ducts, with dilation of preserved segments
Primary sclerosing cholangitis
35
Epidemiology of primary sclerosing cholangitis
- M:F = 2:1; Age: 30-50 years
- First degree relatives of patients with PSC Increased risk of developing the disease
- Association with inflammatory bowel disease, particularly chronic Ulcer. Colitis
(coexistence in about 70% of cases)
36
Imaging of primary sclerosing cholangitis
Characteristic “beading” of contrast medium, in radiographs of the intra-hepatic & extra-hepatic biliary tree
37
Pathogenesis of primary sclerosing cholangitis
- Detection of T-cells in the periductal stroma
- Presence of a plethora of circulating autoantibodies
- Association with Ulcerative Colitis
38
Proposed pathogenic mechanisms of primary sclerosing cholangitis
- Activated T cells (in the gut mucosa) → Accumulation to the liver → Recognition of a
bile duct Ag → Cross Reaction with gut Ags
- Cross-reaction of bile duct Ags with enteric bacteria or bacterial products →
Development of bile duct lesions
39
Morphology of primary sclerosing cholangitis
Fibrosing Cholangitis of bile ducts:
- Lymphocytic inflammatory infiltrate
- Progressive atrophy of the bile duct epithelium
- Obliteration of the lumen
- Concentric peri-ductal fibrosis around affected ducts (“onion-skin fibrosis”) →
Disappearance of the latter → Replacement by a solid, cord-like fibrous scar
- Ectatic and inflamed bile ducts, in between areas of progressive stricture
- Markedly cholestatic liver → Biliary Cirrhosis (with disease progression)
40
Clinical Features of primary sclerosing cholangitis
- Progressive fatigue, pruritus, and jaundice
- Chronic Liver Disease, with weight loss, ascites, variceal bleeding, and
encephalopathy (severe cases)
41
Complications of primary sclerosing cholangitis
- Development of Cholangio-Carcinoma
- Increased incidence of chronic pancreatitis & Hepatocellular Carcinoma
42
Tx of primary sclerosing cholangitis
- No specific medical therapy for PSC
- Cholestyramine, for pruritus
- Endoscopic dilation with sphincterotomy or stenting Symptoms relief
- Liver transplantation (end-stage liver disease)
43
Antibodies commonly found in patients of primary sclerosing. cholangitis :
- Anti-Smooth Muscle Antibodies
- Anti-Nuclear Antibodies (ANAs)
- Rheumatoid Factor
- Atypical p-ANCA Ab (up to 80% of patients)
44
Acute Cholecystitis
Enlarged and tense gallbladder
45
Calculous Cholecystitis
Obstructing stone, in the neck of the gallbladder or the cystic duct
45
Subserosal haemorrhages → Bright red or blotchy (mottled) violaceous to green-black discolouration
Acute Cholecystitis
45
Mild cases: Gallbladder wall
Thickened, oedematous, and hyperaemic
46
Gallbladder Empyema
Intraluminal exudate Pure pus
47
Gangrenous Cholecystitis
Green-black necrotic organ, with small-to-large perforations
47
Emphysematous Cholecystitis
Invasion by gas-forming organisms, mainly Clostridia
48
Clinical features: Cholecystitis
Progressive right upper quadrant or epigastric pain – Mild fever – Anorexia – Tachycardia – Sweating – Nausea and Vomiting
49
Laboratory findings: Cholecystitis
Hyper-bilirubinaemia, in cases of common bile duct obstruction – Mild leukocytosis
50
Sequel to repeated bouts of mild to severe acute cholecystitis, but development of the disease even without antecedent attacks
Chronic cholecystitis
51
Cause: Chronic Cholecystitis
Supersaturation of bile predisposes to both chronic inflammation and stone formation; usually E. coli and Enterococci, can be cultured from the bile (~1/3 of cases)
52
Clinical symptoms (of calculous Chronic Cholecystitis)
Similar to those of the acute form: Range from biliary colic to indolent right upper quadrant pain and epigastric distress
53
Porcelain" Gallbladder
Rare condition; Extensive dystrophic calcifications, intramural
54
Xanthogranulomatous Cholecystitis
Rare condition
Shrunken organ
Focal, nodular or diffuse thickened wall
Histology: Foamy macrophages, cholesterol clefts and multinucleated giant cells, lymphocytes, plasma cells
55
Gallbladder "Hydrops"
Atrophic, chronically obstructed gallbladder with intraluminal secretions
56
Clinical features: Chronic Cholecystitis
Recurrent attacks of either steady or colicky epigastric or right upper quadrant pain
Nausea
Vomiting
Intolerance for fatty foods
57
Complications of Acute superimposed on chronic
- Bacterial superinfection with cholangitis or sepsis
- Gallbladder perforation and focal abscess formation
- Gallbladder rupture with diffuse peritonitis
- Biliary-enteric (cholecystenteric) fistula, with drainage of bile into adjacent organs, entry of air and bacteria into the biliary tree, and potentially, gallstone induced intestinal obstruction (ileus)
-“Porcelain” Gallbladder, with increased risk of cancer
58
Primary Biliary Cirrhosis Clinical Signs and Symptoms:
- Fatigue
- Pruritus
- Hepatomegaly
- Eyelid xanthelasmas
- Hyperpigmentation and inflammatory arthropathy
59
Signs and symptoms of chronic liver disease
Cirrhosis with portal hypertension and visceral bleeding, and hepatic encephalopathy
60
Laboratory findings of Primary Biliary Cirrhosis:
Elevated serum levels of Alkaline Phosphatase (ALP), γ-glutamyltransferase (γ-GT) & Cholesterol
Hyper-bilirubinaemia (later in the disease)
Anti-mitochondrial antibodies (90-95% of cases)
61
Pathogenesis of Primary Biliary Cirrhosis
- Abnormal expression of MHC class II molecules on the bile duct epithelial cells
- Accumulation of autoreactive T cells around bile ducts
- Reaction of anti-mitochondrial antibodies to hepatocytes, or of other antibodies against cellular components (nuclear pore proteins, & centro-meric proteins)
62
Macroscopic features of Primary Biliary Cirrhosis:
Early Stages:
Appearance: Normal liver size and appearance.
Weight: Normal or slightly increased.
Progression:
Color: Liver turns green due to bile stasis (accumulation of bile).
Surface: Fine granular capsule develops due to the formation of fibrous septa.
Cirrhosis: Well-developed, uniform micronodular cirrhosis occurs.
Weight: Liver weight decreases.
Pre-Cirrhotic Stage:
Portal Tracts: Infiltration by lymphocytes, macrophages, plasma cells, and eosinophils.
Bile Ducts: Infiltration of interlobular bile ducts by lymphocytes and presence of non-caseating granulomatous inflammation.
Further Progression:
Bile Flow Obstruction: Leads to progressive secondary hepatic damage.
Portal Tracts: Show bile ductular proliferation, inflammation, and necrosis of surrounding liver tissue.
Cholestasis: Generalized cholestasis develops within the liver parenchyma.
Fibrosis: Persistent portal tract scarring and bridging fibrosis eventually lead to cirrhosis.
In essence, the disease progresses from initial inflammation and bile duct damage to significant liver scarring and dysfunction, culminating in cirrhosis.
63
Clinical features of Primary Biliary Cirrhosis:
- Extremely insidious onset, with symptom-free disease for many years
- Eventually, development of pruritus, fatigue, and abdominal discomfort with
subsequently secondary features: Skin pigmentation, Xanthelasma, Steatorrhoea,
and Vitamin D malabsorption-related Osteomalacia and/or Osteoporosis
- Portal hypertension and Variceal Bleeding (end stages of the disease)
- Individuals with PBC may also have extrahepatic manifestations of autoimmunity
(Sjögren Syndrome, Systemic Sclerosis, Thyroiditis, Reumatoid Arthritis,
Membranous Glomerulonephritis, and Coeliac Disease)
64
Complications of primary biliary cirrhosis
- Increased risk for HCC development
Death, due to:
- Liver failure
- Massive variceal haemorrhage
- Intercurrent infection
65
TX of primary biliary cirrhosis
- Ureodeoxycholic acid, if started early, can provide complete remission & prolong survival in 25% to 30% of cases
- Liver transplant., for cases with end-stage liver disease
