Histo: Diseases of the Pancreas and Gallbladder Flashcards
What are the main components of the exocrine part of the pancreas?
Acini and ducts
What is the endocrine component of the pancreas called?
Islets of Langerhans
Define acute pancreatitis.
Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes
List some causes of acute pancreatitis.
Duct obstruction
- Gallstone (50%)
- Trauma
- Tumours
Metabolic/toxic
- Alcohol (33%)
- Drugs (e.g. thiazides)
- Hypercalcaemia
- Hyperlipidaemia
Ischaemia
- Shock
- Hypothermia
Infection/inflammation
- Mumps
- Autoimmune
Idiopathic (15%)
NOTE: gallstones + alcohol are KEY
What is the basic common pathogenesis of both gallstone and alcohol-induced acute pancreatitis?
Duct obstruction
The rest of the etiologies cause acute pancreatitis via direct acinar injury
Describe how gallstones causes acute pancreatitis
- Gallstones can obstruct the bile ducts distal to where the common bile ducts and pancreatic ducts join
- This leads to the reflux bile up the pancreatic ducts which can damage the acini
- Digestive proenzymes are released which then become activated
Describe how alcohol can cause acute pancreatitis.
It leads to spasm/oedema of the sphincter of Oddi and the increasing the viscosity of pancreatic secretions. Both of these cause duct obstruction.
Describe the three main patterns of injury in acute pancreatitis
- Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction)
- Perilobular - necrosis at the edges of the lobules (usually due to poor blood supply)
- Panlobular - develops as periductal or perilobular inflammation worsens
Outline the pathway of inflammation in acute pancreatitis.
Activated enzymes → acinar necrosis → release of more enzymes
What is saponification?
- Lipases break down fats to release free fatty acids
- Calcium binds to the free fatty acids forming soaps
(yellow-white foci)
List some complications of acute pancreatitis.
Local:
- Pseudocyst formation
- Abscesses
Systemic:
- Sepsis
- ARDS
- DIC
- Shock
- Hypoglycaemia
- Hypocalcaemia
Define pseudocyst.
- A collection of fluid lined by fibrous tissue (no epithelial lining)
- They are rich in pancreatic enzymes and necrotic material
They may resolve, compress adjacent structures, become infected, or perforate
More commonly associated with chronic pancreatitis but can occur with acute
List some causes of chronic pancreatitis.
Metabolic/Toxic:
- Alcohol (80%)
- Haemochromatosis
Duct obstruction:
- Gallstones
- Abnormal anatomy
- Cystic fibrosis
Autoimmune
Tumours
Idiopathic
Outline the pattern of injury in chronic pancreatitis.
- Chronic inflammation with parenchymal fibrosis and loss of parenchyma
- There will be duct strictures with calcified stones with secondary dilatations
Describe the difference between WBCs seen in acute vs chronic pancreatitis
- Acute - neutrophils
- Chronic - lymphocytes
List some complications of chronic pancreatitis.
- Malabsorption
- Diabetes mellitus
- Pseudocysts
- Pancreatic carcinoma
What radiographic feature is diagnostic of chronic pancreatits?
Visible pancreatic calcifications on AXR
What is the cytological feature is characteristic of autoimmune pancreatitis?
Large numbers of IgG4 positive plasma cells typically found around the ducts
How is autoimmune pancreatitis treated?
Steroids - usually responds well
Name 3 categories of pancreatic neoplasms
- Carcinomas
- Cystic neoplasm (cystadenomas)
- Neuroendocrine tumours (islet cell tumours)
What are the two types of pancreatic carcinomas and which is more common?
- Ductal (85% of all pancreatic neoplasms)
- Acinar
Many ductal carcinomas may actually arise from acini after a process called acini-ductal metaplasia (these ductal carcinomas have a different natural history to truly ductal carcinomas)
Name two types of cystic neoplasm of the pancreas.
- Serous cystadenoma - contains serous secreting epithelium
- Mucinous cystadenoma - contains mucous secreting epithelium
Usually benign
List some risk factors for pancreatic cancer.
- Smoking
- BMI and dietary factors
- Chronic pancreatitis
- Diabetes mellitus
Name two types of dysplastic precursor lesion that ductal carcinoma can arise from.
- Pancreatic intraductal neoplasia (PanIN)
- Intraductal mucinous papillary neoplasm
Which mutation is very common in ductal cancer?
K-ras (95% of cases)
Describe the macroscopic appearance of ductal carcinoma?
- Gritty and grey
- Invades adjacent structures
How does tumour location affect latency period in ductal carcinoma?
Tumours affecting the head of the pancreas present earlier (with biliary obstruction)
Describe the microscopic appearance of ductal carcinoma.
- Adenocarcinomas (secrete mucin and form glands)
- Mucin-secreting glands are set in desmoplastic stroma
What is the most common site of ductal carcinoma?
Head (60%) > Body > Tail>diffuse
NOTE: opposite for neuroendocrine tumours (more common in the tail)
What are the usual sites of metastasis of ductal carcinoma?
- Direct: bile ducts, duodenum
- Lymphatic: lymph nodes
- Blood: liver (most common site of metatasis)
- Serosa: peritoneum
Perineural spread is common
List some complications of ductal carcinoma.
- Metastasis
- Chronic pancreatitis
- Venous thrombosis (migratory thrombophlebitis) - Trosseau sign of malignancy
By what mechanism does pancreatic cancer cause migratory thrombophlebitis?
- Circulating pancreatic cancer cells release mucous which activates the clotting cascade
List some key features of pancreatic neuroendocrine neoplasms.
- Usually non-secretory
- Contains neuroendocrine markers (e.g. chromogranin) - can be measured as a screening test for neuroendocrine tumours
- May be associated with MEN1
What is the most common type of functional (secretory) neuroendocrine tumour?
Insulinoma (derived from beta cells)
List some factors that increase the likelihood of developing gallstones.
- Obesity
- Age
- Gender (females)
- Ethnic factors
- Hereditary
- Drugs (e.g. oral contraceptive)
- Rapid weight loss
What are the two types of gallstone and what are their distinguishing features?
Cholesterol (>50% cholesterol)
- May be single
- Mostly radiolucent (NOT seen on AXR)
Pigment
- Often small with multiple stones
- Contain calcium salts of unconjugated bilirubin
- Mostly radio-opaque
List some complications of gallstones.
- Bile duct obstruction
- Acute and chronic cholecystitis
- Gallbladder cancer
- Pancreatitis
Most are asymptomatic
What is the main cause of acute and chronic cholecystitis
Gallstone (associated in 90% of cases)
What is the term used to describe diverticula of the gallbladder? How do they form?
Rokitansky-Aschoff sinuses - form as a result of the gallbladder contracting against an obstruction
Which type of cancer is gallbladder cancer?
Adenocarcinoma
NOTE: it is technically a type of cholangiocarcinoma
90% associated with gallstones