Histo: Diseases of the Pancreas and Gallbladder Flashcards
What are the main components of the exocrine part of the pancreas?
Acini and ducts
Define acute pancreatitis.
Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes
List some causes of acute pancreatitis.
- Duct obstruction (gallstones, tumour, trauma)
- Metabolic/toxic (alcohol, drugs, hypercalcaemia, hyperlipidaemia)
- Poor blood supply
- Infection/inflammation (viruses e.g. mumps)
- Autoimmune
- Idiopathic
Describe how alcohol can cause acute pancreatitis.
It leads to spasm/oedema of the sphincter of Oddi and the formation of protein-rich pancreatic fluid which is thick and causes an obstruction
NOTE: most other causes of acute pancreatitis will do so via direct acinar injury
Describe the three main patterns of injury in acute pancreatitis and describe what they result from.
- 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 - results from worsening periductal or perilobular inflammation
Outline the pathway of inflammation in acute pancreatitis.
Activated enzymes → acinar necrosis → release of more enzymes
What is saponification?
- Lipases break down fats around the pancreas to release free fatty acids
- Calcium binds to the free fatty acids forming soaps
- this leaves white chalky deposits
- this can eventually cause hypocalaemia
Complication of acute pancreatitis
List some complications of acute pancreatitis.
- Pseudocyst formation, abscesses
- Shock
- Hypoglycaemia
- Hypocalcaemia (from saponification)
Define pseudocyst.
- A collection of fluid without an epithelial lining
- They are rich in pancreatic enzymes and necrotic material
- They are lined by fibrous tissue
NOTE: they may resolve, compress adjacent structures, become infected or perforate
List some causes of chronic pancreatitis.
- Metabolic/Toxic: alcohol (80%), haemochromatosis
- Duct obstruction: gallstones, abnormal anatomy, cystic fibrosis (mucoviscoidosis)
- Tumours
- Idiopathic
- autoimmune (IgG4 produced by plasma cells)
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
List some complications of chronic pancreatitis.
- Malabsorption
- Diabetes mellitus
- Pseudocysts
- Pancreatic carcinoma
What is the characteristic feature of autoimmune pancreatitis?
Large numbers of IgG4 positive plasma cells typically found around the ducts
How is autoimmune pancreatitis treated?
Steroids - usually responds well
What are the two types of pancreatic cancer and which is more common?
- Ductal (85%)
- Acinar (15%)
NOTE: 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
- Mucinous cystadenoma
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 pancreatic cancer?
K-ras (95%)
Describe the macroscopic appearance of ductal carcinoma?
Gritty and grey
Invades adjacent structures
NOTE: tumours in the head of the pancreas present earlier
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%)
NOTE: neuroendocrine tumours are more common in the tail
What are the usual sites of metastasis of ductal carcinoma?
- Direct: bile ducts, duodenum
- Lymph nodes
- Blood: liver
- Serosa: peritoneum
List some complications of ductal carcinoma.
- Metastasis
- Chronic pancreatitis
- Venous thrombosis (migratory thrombophlebitis)
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 during CT/MRI scans)
- May be associated with MEN1
- is a tumour of the islet cells (as can be releasing endocrine material)
Is functional or nonfunctional
functional i.e. insulinoma
What is the most common type of functional neuroendocrine tumour?
Insulinoma
List some factors that increase the likelihood of developing gallstones.
- Age
- Gender (females)
- Ethnic factors
- Hereditary
- Drugs (e.g. oral contraceptive)
What are the two types of gallstone and what are their distinguishing features?
- Cholesterol
- May be single
- Mostly radiolucent (NOT seen on AXR)
- Pigment
- Often multiple
- Contain calcium salts of unconjugated bilirubin
- Mostly radio-opaque
List some complications of gallstones.
- Most are asymptomatic
- Bile duct obstruction
- Acute and chronic cholecystitis
- Gallbladder cancer
- Pancreatitis
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
Function of CCK and secretin?
CCK - causes gall bladder contraction so stimulates digestion of fat and protein
Secretin - controls gastric acid secretion and buffers it with HCO3- released from the pancreas
Where are the endocrine hormones produced? And what cells produce what?
Islets of langerhans!
Alpha - glucagon (to increase blood glucose)
Beta cells - insulin
Delta cells - somatostatin (which inhibits the hormones above)
Where are the exocrine materials made in the pancreas/
Acini
In the acinar cells - peptidases, lipases, amylase
Microvascular complications of diabetes?
Retinopathy
Glomerulonephritis / nephropathy
Peripheral neuropathy
Macrovascular complications of diabetes?
IHD
PVD
CVA
Diagnosis of diabetes?
Fasting glucose >7mmol/L
Random plasma glucose >11.1 mmo/L
HbA1c >48mmol/L
Pathophysiology of t1dm
autoimmune destruction of beta cells by cd4+ and cd8+ t lymphocytes
Scoring for acute pancreatitis?
GLASGOW scale >=3 -> severe
blood markers for acute pancreatitis
amylase (but only transient)
lipase is more sensitive
histology of acute pancreatitis
coagulative necrosis
complications of acute pancreatitis
saponification (15%) (+ thus hypocalcaemia)
hypoglycaemia
what is a cholangiocarcinoma?
cancer of the bile ducts
what are rokitansky aschoff sinuses?
diverticula in the gall bladder, can cause chronic cholecystitis
procedure for pancreatic cancer
whipple’s
Blood marker for pancreatic cancer
CA19.9
clinical presentation of pancreatic cancer
weight loss, upper abdo and back pain
painless jaundice
steatorrhoea
DM
virchow’s node
Courvoisier’s sign (painless jaundice and enlarged gall bladder)
abdominal mass
where are pancreatic cancers usually?
head
what type of cancer is pancreatic carcinoma
ductal adenocarcinoma
risk factors for pancreatic cancer
FAP, HNPCC, smoking, diet
what is zollinger ellison syndrome
Gastrinoma causing recurrent ulceration
causes pancreas to secrete lots and lots of gastrin, a hormone that stimulates production of gastric acid, leading to severe gastrointestinal ulcers
what is men1
PPP -
pit adenoma
parathyroid hyperplasia/adenoma
pancreatic endocrine tumour
what is men2a
Parathyroid, medullary thyroid and phaeochromocytoma
what is men 2b
mucosal neuromas, marfanoid body, medullary thyroid, phaeo
what is the name of the marker for ct/mri scans of neuroendocrine tumours?
chromograffin
what is a VIPoma
pancreatic neuroendocrine tumour, causes watery diarrhoea
