Week 4 - HEPATOBILIARY Flashcards
Cholecystitis, Cholelithiasis + Cancer, Pancreatitis, Pancreatic Cancer
1
Q
What is commonest cause of cholecystitis?
A
Cholelithiasis - 95%
2
Q
What is the pathogenesis of cholecystitis?
A
- obstruction
- stasis (of bile)
- increased pressure in gall bladder
- ischaemia
- mucosal damage by bile salts (detergent) –> therefore inflammation + secondary infections (e.g. E. coli)
3
Q
What are the complications of cholecystitis?
A
- cholangitis (inflammation spreads to biliary tree –> secondary biliary cirrhosis)
- empyema
- rupture
- peritonitis
- gall stone ileus
4
Q
What are the clinical features of acute cholecystitis?
A
- biliary pain –> steady, progressive, RUQ to R shoulder radiation
- obstructive jaundice (20% cases) –> when total obstruction of CBD occurs
5
Q
What is morphology of acute cholecystitis?
A
Acute inflammation
-neutrophils, oedema, vasodilation
Haemorrhage
6
Q
What disorder is suspected if serum amylase is increased?
A
Acute pancreatitis
7
Q
What is gall stone ileus?
A
- complication of acute cholecystitis
- one of the gall stones enters GIT + causes obstruction
8
Q
What is a key difference between acute and chronic cholecystitis?
A
- markedly thicker and more concentrated bile in chronic –> BILIARY GRAVEL
- also.. pts. with chronic cholecystitis typically present with nausea/vomiting + intolerance for fatty food
9
Q
What is the microscopy of chronic cholecystitis?
A
- chronic inflammation
- thick fibrotic wall
- aschoff-rokitansky sinuses –> excess luminal pressure pushes glands through muscular layer (herniation)
- atrophy of mucosa + muscle hypertrophy
10
Q
What are aschoff-rokitansky sinuses?
A
-herniation of mucosal glands through the mucosa seen in chronic cholecystitis
11
Q
What is acalculous cholecystitis?
A
- cholecystitis without gall stones
- seen in pts. with sepsis, burns, hypotension, trauma, diabetes
- secondary to wall ischaemia –> decreased protection and movement –> stasis
- mild biliary symptoms (as primary disease is prominent)
- increased risk of gangrene or perforation
12
Q
What is cholesterolosis?
A
- type of chronic cholecystitis
- increased cholesterol accumulates within the folds of the mucosa causing hundreds of small polyps
- STRAWBERRY GALL BLADDER –> as multiple polyps cause characteristic gross feature
13
Q
What are risk factors for cholecystitis/cholelithiasis?
A
FFFF
- female
- fat
- forty
- fertile
- fair-skinned
- oral contraceptives
- disorders of bile metabolism
- hyperlipidaemia
- diabetes
14
Q
What are the 2 major types of gall stones?
A
- Mixed cholesterol stones (80%)
- stones with calcium, bile, blood and increased cholesterol - Pigment stones (20%)
- black –> hemoglobin (hemolytic anemia)
- brown –> calcium increased (infections/IBD)
- yellow –> pure cholesterol (familial hyperlipidaemia)
15
Q
What are the 3 triad features of cholelithiasis?
A
- RUQ steady pain
- fever
- leukocytosis
- progressive –> R shoulder/back radiation of pain
- steady NOT colicky pain
- *BUT 70-80% of pts. are asymptomatic
16
Q
What is the typical chronic presentation of cholelithiasis?
A
Fat intolerance
-indigestion, stomach upsets, flatulence following fatty foods
*clay stools (fat in stools due to lack of bile digesting fats) –> foul-smelling, sticky, pale
17
Q
What is cholecystokinin?
A
Hormone released in response to fat food ingestion causing gall bladder contraction –> bile secretion
18
Q
What is bile composed of and how is cholesterol made soluble?
A
- cholesterol
- bile salts
- bile pigment
*cholesterol made soluble by bile salts + lecithins (detergents) –> therefore, increased cholesterol or decreased bile salts = GALL STONES
19
Q
What are the 4 pathogenetic factors of cholelithiasis?
A
- increased cholesterol/decreased bile salts
- stasis of bile
- pancreatic enzyme reflux into gall bladder
- infection
*deposition of cholesterol crystals leading to stone formation
20
Q
What are the 4 etiological factors for cholelithiasis?
A
- Age/Sex: - female, fair, fat, forty, fertile
- Enironmental: - increased estrogen, OCP, pregnancy, obesity, rapid wt. loss
- Acquired: - hemolysis, infection, bile stasis
- Hereditary: - ABCG8 gene mutation (sterol transporter –> therefore increased cholesterol)
21
Q
True or False?
Gall stones are typically visible on an X-ray
A
False
- typically radioluscent (not seen on X-ray)
- ONLY visible if calcium concentration in stone is markedly increased
22
Q
Why are gall stones faceted in appearance?
A
- stones present for many yrs
- rubbing of stones against each other causes faceting –> joint like surfaces
23
Q
What is the morphology of mixed cholesterol gallstones (commonest)?
A
- yellowish, golden, grey-brown stones
- shiny, faceted stones
- varying colour based on contents
- biliary gravel –> stasis
- chol. >50% + bile + cells + blood + calcium (10%)
24
Q
What is the morphology of pure cholesterol gall stones?
A
- round
- yellow
- spiky surface –> bleeding
*marked hypercholesterolemia (usually familial)
25
What is the morphology of pigment stones in hemolytic anemia?
- dark/black
- friable soft stone (can crush in hand - powdery)
- increased bilirubin (from hemolytic anemias)
- thick wall; neck obstruction
26
What is choledocholithiasis?
gall stones present in the CBD
27
What are complications of cholelithiasis?
- acute cholecystitis --> COMMONEST
- choledocholithiasis
- pancreatitis (stone obstructs distal CBD causing bile reflux into pancreas
- acute/chonic cholangitis
- gall stone ileus
- gall bladder cancer
- cholangiocarcinoma
28
What is the commonest tumour of gall bladder?
adenocarcinoma
| -tumours are v. rare
29
What are the 2 types of gall bladder tumours?
1. adenocarcinoma
- increase F
- abdo. pain, anorexia, increased ALP
- late Dx./poor prognosis
2. cholangiocarcinoma
- bile duct adenocarcinoma
- early obstruction
- treated early/better prognosis
- irregular dysplastic glands
30
What is Klatskin tumour?
-bile duct adenocarcinoma occuring at the hilum junction
31
True or False?
| Pancreas is predominantly en endocrine organ
False
- predominantly exocrine (digestive juices/enzymes)
- endocrine 1-2%
32
What is meant by pancreatic enzymes being proenzymes?
Enzymes are lytic but inactive
33
What activates the pancreas and what protective mechanism is in place to prevent overactivation?
- activated by trypsin in duodenum
| - acini secrete trypsin inhibitors
34
What are the 3 congenital pancreas disorders and briefly describe the commonest one?
1. Pancreas divisum (commonest - 3%)
- no wirsung duct (duct that joins minor + major ducts)--> leads to obstruction --> chronic pancreatitis
2. Annular pancreas
- pancreas encircles duodenum
3. Ectopic pancreas
- pancreatic tissue in other organs (commonly stomach/duodenal wall)`
35
What is the key diagnostic test for pancreatitis?
- serum amylase (<24hrs)
| - serum lipase (>72hrs)
36
What is contraindicated in terms of investigations of pancreatitis?
BIOPSY
- hazardous
- don't ouch the pancreas
- can activate and cause increase enzyme secretion
37
Where is the pancreas located?
behind the stomach
| -it is a retroperitoneal organ
38
Outline microscopy of a normal pancreas
Acini (exocrine)
-digestive proenzymes released to duodenum (activated here)
Islets of langerhans (endocrine)
-clusters of endocrine cells (alpha, beta, delta)
39
What is acute pancreatitis?
- acute, reversible inflammation of the pancreas due to spreading enzymatic autodigestion - "eating itself"
- causes haemorrhage + fat necrosis --> shock and multi-organ failure
- activation/defective inactivation of trypsin
40
What is the etiology of acute pancreatitis? and specify the commonest.
COMMONEST --> alcohol (M) + gall stones (F) - 80%
- obstruction to outflow; acinar cell injury; defective intracellular transport
- shock, immune, mumps, hypercalcemia, drugs, surgery, ERCP (DON'T touch the pancreas)
41
What enzymes are released in pancreatic damage and what do each result in?
- lipase --> fat necrosis (inflammation)
- protease --> BV injury (bleeding)
- amylase --> diagnostic test
42
Outline pathogenesis of acute pancreatitis
-alcohol and gallstones result in ductal obstruction, acinar cell injury and defective intracellular transport
Therefore:
- release/activation of pancreatic enzymes
- damage to pancreas occurs (inflammation)
- increased serum amylase
- increased lipase --> fat necrosis
- increased proteases --> BV injury (bleeding)
43
Why does pancreatitis epigastric pain radiate to the back?
It is a retroperitoneal organ located at the back (behind the stomach)
44
What are the clinical features of acute pancreatitis?
- constant, severe epigastric pain radiating to the back
- abdominal distension, guarding, rigidity
- diminished or absent bowel sounds (functional intestinal obstruction)
- mild jaundice (CBD obstruction)
- fever
- vomiting
- DIC, shock, fat necrosis, haemorrhage (proteases)
- respiratory/circulatory failure
- hypocalcemia
- increased amylase/lipase
45
What is the pathogenesis of hypocalcemia in acute pancreatitis?
- lipase released from damaged/activated cells
- fat necrosis
- increased fatty acids
- fatty acids bind calcium
- increased calcium is dragged down and excreted with fatty acids --> hypocalcemia + calcium soaps
46
True or False?
| Only lipase is increased in chronic pancreatitis
True
- amylase (<24hrs)
- lipase (>72hrs)
47
What are the 3 causes of acute pancreatitis in an alcoholic?
1. duct obstruction
2. acinar cell injury
3. defective intracellular transport
48
What is Grey Turner's and Cullen's sign?
Grey Turner's
-discolouration of flanks/posterior portion of abdomen due to seepage of blood from proteases causing haemorrhage
Cullen's
- tracking of leaked blood to umbilicus
- periumbilical ecchymosis
49
What are gross features of acute pancreatitis?
- oedema + inflammation
- haemorrhage
- fat necrosis (calcium soaps --> white spots indicating fatty acid release)
50
What are the microscopic features of acute pancreatitis?
- fat necrosis (opaque fat cells)
- inflammatory cells increased
- haemorrhage
51
What are laboratory diagnostic findings in acute pancreatitis?
- FBC --> increased neutrophils/leukocytes
- increased serum amylase/lipase
- decreased albumin when severe
- hypocalcemia (fat necrosis)
- BSLs --> hyperglycemia if loss of endocrine part
- ALP/bilirubin --> mild increase if CBD obstruction due to gall stones
52
What is chronic pancreatitis?
- recurrent acute pancreatitis --> + fibrosis, scarring and atrophy of acini & ducts with calcification
- loss of pancreatic function
- malabsorption, decreased albumin, wt. loss (improper digestion)
- pleural effusions ?
53
What are complications of chronic pancreatitis?
- pseudocyst
- T1DM (endocrine cell damage)
- cancer
- steatorrhea/malabsorption --> pale stools
54
What is a pancreatic pseudocyst?
- a collection of fluid around the pancreas. The fluid in the cyst is usually pancreatic juice that has leaked out of a damaged pancreatic duct
- it has no epithelial lining
- complication of chronic pancreatitis
55
What are microscopic features of chronic pancreatitis?
- extensive fibrosis
- acinar cell atrophy
- dilated ducts
- plenty of inflammation
56
What is the commonest and most clinically significant pancreatic tumour?
Adenocarcinoma
- commonly arises in head of pancreas
- 4th common cancer (next to colon)
- late age (>60yrs)
- increased in males
- highest mortality (5yr survival <5%) - :(
57
What are the risk factors for pancreatic cancer?
- smoking
- diet (increased calorie, fat, meat, salt, fried/refined foods)
- chronic pancreatitis
- diabetes
- MEN
- colon cancer
58
What are the gene mutations associated with pancreatic cancer and which is the most common?
```
CDK2NA = most common
Also:
-K-ras
-BRCA1/2
-MLH1/MSH2
-SPINK1 --> hereditary pancreatitis
```
59
What is the gene mutation for herditary pancreatitis?
SPINK1
60
What is the pathogenesis of pancreatic cancer?
Risk factors --> genetic mutations (K-ras) --> PanIN (pancreatic in situ neoplasia) --> invasive carcinoma
61
What are the clinical features of pancreatic carcinoma?
- epigastric pain --> radiates to the back
- significant weight loss
- depression*
- jaundice (CBD obstruction)
- Courvoisier's sign --> palpable gall bladder + jaundice
- Trousseau's sign --> migratory thrombophlebitis
- T1DM --> beta cell destruction
62
What are the gross and microscopic features of pancreatic cancer?
Gross:
- near head of pancreas
- involves pancreatic duct + CBD
- hard, irregular white tissue
Micro:
- irregular dysplastic glands in dense stroma (fibrous tissue)
- fibrosis
- irregular nuclei
63
Outline pancreatic cancer staging (T1 --> T4)
T1: - <2cm, no ductal incolvement
T2: - >2cm, with ductal involvement
T3: - invades duodenum, bile duct, major veins, or peripancreatic tissues
T4: - invades stomach, spleen, colon or larger arteries
64
What is the pathogenesis of pedal oedema in chronic pancreatitis?
Lack of absorption/protein digestion --> hypoalbuminemia --> decreased oncotic pressure --> PEDAL OEDEMA (leaky capillaries)
