(60) Disease of the pancreas Flashcards
Describe the exocrine function of the pancreas
Most of pancreas (85%)
- Secrets digestive enzymes (trypsin, lipase, phospholipase, elastase, amylase) which require activation
- secretes from glands through ducts to duodenum
Which digestive enzyme secreted by the pancreas is a marker of pancreatic inflammation?
Amylase
Describe the endocrine function of the pancreas
- islets of Langerhans
- secrete peptide hormones into the blood eg. insulin and glucagon
Which cells secrete insulin and glucagon?
Islets of langerhans
glucagon = alpha cells insulin = beta cells
What is pancreatitis?
Inflammation of the pancreas (can be acute or chronic)
What are the clinical features of acute pancreatitis?
- sudden onset of severe abdo pain radiating to back
- nausea and vomiting
- may be mild (recovery within 5-7 days) but can be serious with high mortality
- raised serum amylase/lipase (over 3x normal)
Serum levels of what are raised in acute pancreatitis?
Amylase/lipase
What causes 50% of cases of acute pancreatitis?
Gallstones
What causes 25% of cases of acute pancreatitis?
Alcohol
What are the more rare causes of acute pancreatitis?
- vascular insufficiency
- viral infections eg. mumps, coxsackie B
- hypercalcaemia
- ERCP
How many cases of acute pancreatitis are idiopathic?
10%
List the causes of acute pancreatitis
- gallstones
- alcohol
- vascular insufficiency
- viral infections (mumps, coxsackie B)
- hypercalcaemia
- ERCP
- idiopathic
Why do you get increased serum amylase in acute pancreatitis?
There is leakage and activation of pancreatic enzymes - amylase released into the blood
Describe the pancreas in mild acute pancreatitis
Swollen gland with fat necrosis
Describe then pancreas in severe acute pancreatitis
Swollen, necrotic gland with fat necrosis and haemorrhage
Grey Turner’s sign and Cullen’s sign
What do you get in fat necrosis?
Chalky white material containing calcium salts that have been freed up by lipase-mediated cleavage of fatty acids
What is Grey Turner’s sign? (seen in severe acute pancreatitis)
Haemorrhage into the subcutaneous tissues of the flank
What is Cullen’s sign?
Superficial oedema and bruising in the subcutaneous fatty tissue around the umbilicus
Other than swelling, necrosis and haemorrhage, what else do you get in acute pancreatitis?
- hypocalcaemia (fatty acids bind calcium ions)
- hyperglycaemia
- abscess formation
- pseudocysts
What are the complications associated with acute pancreatitis?
- shock
- intravascular coagulopathy
- haemorrhage
- pseudocysts
What are pseudocysts in acute pancreatitis?
Collections of pancreatic juice secondary to duct rupture
What is chronic pancreatitis?
Progressive inflammatory disorder in which parenchyma of the pancreas is destroyed and replaced by fibrous tissue
- irreversible destruction of the exocrine tissue, followed by destruction of the endocrine tissue
What 2 conditions does chronic pancreatitis lead to?
Malnutrition and diabetes
Describe the ways in which acute and chronic pancreatitis are not two distinct disease but rather a continuum
- recurrent acute can develop chronic pancreatitis
- overlapping causative factors
- both genetic and environmental
- experimental protocols can be modified to induce each condition
Most cases of chronic pancreatitis are due to what?
Alcohol or idiopathic (when exclusion cystic fibrosis)
Other than alcohol, what else is a strong independent risk factor for pancreatitis?
Cigarette smoking
What genetic mutations can cause chronic pancreatitis?
- CFTR
- PRSS1
- SPINK 1
What are the toxic causes of chronic pancreatitis?
- alcohol
- smoking
- drugs
- hypercalcaemia
- hyperparathyroidism
- infections
List the causes of chronic pancreatitis
- toxic (alcohol, smoking, hypercalcaemia etc)
- genetic
- obstruction of main duct (cancer, scarring)
- recurrent acute pancreatitis
- autoimmune
- idiopathic
Describe the clinical features of chronic pancreatitis
- repeated episodes of acute pancreatitis
- intermittent abdo pain, back pain and weight loss
- fibrosis of exocrine tissue - can mimic carcinoma macroscopically and microscopically
What are the complications associated with chronic pancreatitis?
- malabsorption of fat (lack of lipases)
- diabetes (late feature)
- pseudocysts
- stenosis of common bile duct/duodenum
- mortality of 50% within 20-25 years
Chronic pancreatitis leads to malabsorption of fat due to lack of lipases. What does this cause?
- steatorrhoea
- impairment of fat soluble vitamins absorption (vitamins A, D, E and K)
- diarrhoea, weight loss, and cachexia
Which are the fat-soluble vitamins?
Vitamins A, D, E and K
What is the mortality rate of chronic pancreatitis?
Nearly 50% within 20-25 years of disease onset
What is seen on a scan in chronic pancreatitis?
- localised, irregular involvement of the gland early on, later global atrophy
- dilated and distorted ducts
- calculi (especially she alcohol-induced)
- fatty replacement
- pseudocyst formation
What is the most common type of pancreatic cancer? (90% of all pancreatic neoplasms)
Pancreatic adenocarcinoma (ductal adenocarcinoma) - PDAC
Who gets pancreatic adenocarcinoma?
1.3 males: 1 female
60-80 years, rare before 40
What is the prognosis of pancreatic adenocarcinoma?
- 5 year survival = 4%
- Mean survival untreated = 3-5 months/10-20 months with surgery
- only 10-20% resectable at time of diagnosis
- almost universally fatal
What are the risk factors for pancreatic adenocarcinoma?
- CIGARETTE SMOKING
- heavy alcohol intake
- diet rich in red meats
- obesity
- hereditary cancer syndromes (10%)
- chronic pancreatitis
Where is the pancreas does pancreatic adenocarcinoma affect?
- head of pancreas (60-70%)
- tail (10-15%)
- body (5-15%)
- diffuse involvement (5-15%)
What are the signs and symptoms of pancreatic adenocarcinoma?
- epigastric pain, radiating to back
- weight loss
- painless jaundice
- pruritus
- nausea
- Trousseau’s syndrome
- Courvoisier’s sign
- diabetes
What is pruritus? (symptom of pancreatic adenocarcinoma)
Severe itching of the skin
What is Trousseau’s sign of malignancy? (sign of pancreatic adenocarcinoma)
Thrombophlebitis which is recurrent or appearing in different locations over time = migratory thrombophlebitis
What is Courvoisier’s law?
States that in the presence of a palpably enlarged gallbladder which is nontender and accompanied with mild painless jaundice, the cause is unlikely to be gallstones (palpable gallbladder without pain = sign of pancreatic adenocarcinoma)
In pancreatic adenocarcinoma, there may be distant metastases where?
- liver
- peritoneum
- lung
What are the poor prognostic factors of pancreatic adenocarcinoma?
- extension of tumour outside of the pancreas
- metastatic spread to local lymph nodes
- vascular and perineural invasion
- grade of differentiation
What hereditary cancer syndromes are associated with 10-15% of pancreatic adenocarcinomas?
- HNPCC
- FAMMM
- familial breast cancer
- ataxia-telangiectasis
- von hippel-lindau
- familial pancreatitis
- peutz-jeghers
Name another type of pancreatic cancer
Pancreatic neuroendocrine tumours (less than 3% of all pancreatic neoplasms)
What is the causes of recent increasing incidence of pancreatic neuroendocrine tumours?
Improvements in imaging and increased awareness (so increased diagnosis)
Who gets pancreatic neuroendocrine tumours?
20-60 years
M=F
There is an increased risk of pancreatic neuroendocrine tumours in which syndromes?
- MEN1
- von Hippel Lindau
What are the features of well-differentiated neuroendocrine tumours?
- uncommon
- any age, rare in children
- 7-13% multiple (MEN-1)
- 15-35% non-functioning
- single tumours often produce multiple hormones but usually single hyper-functional syndrome
What are the features of poorly differentiated neuroendocrine carcinomas?
- rare
- males more than females
- 40-75 years
- advanced disease at presentation
- prognosis without treatment = 1-2 months
- prognosis with chemotherapy = up to 50 months
Name 6 types of functioning PENs
- insulinoma
- glucagonoma
- gastrinoma
- somatostatinoma
- VIPoma
- PP-cell PEN
What cell type do each of the functioning PENs form in?
- insulinoma = B cell
- glucagonoma = a cell
- gastrinoma = G cell
- somatostatinoma = delta cell
- VIPoma = unknown
- PP-cell PEN = PP cells
What syndrome occurs in insulinoma and what are the clinical findings?
Insulinoma syndrome
- hypoglycaemia
What syndrome occurs in glucagonoma and what are the clinical findings?
Glucagonoma syndrome
- stomatitis
- rash
- diabetes
- weight loss
- hyperglycaemia
What syndrome occurs in gastrinoma and what are the clinical findings?
Zollinger-Ellison syndrome
- peptic ulcer
- diarrhoea
(gastrin produces stomach acid)
What syndrome occurs in stomatostatin and what are the clinical findings?
Somatostatinoma syndrome
- diabetes
- cholelithiasis
- hypochlorhydria
What syndrome occurs in VIPoma and what are the clinical findings?
Verner-Morrison syndrome
- diarrhoea
- hypokalaemia
- achlorhydria
What syndrome occurs in PP-cell PEN and what are the clinical findings?
None
Describe the macroscopic features of pancreatic neuroendocrine tumours?
- usually well-circumscribed, sometimes encapsulated
- solid
- 10- over 50mm
- occur anywhere in pancreas
- can be multiple
