Histopathology - Pancreatic Disease Flashcards
What is the role of the pancreas?
- Produces 2L a day of enzymic HCO3- rich fluid, stimulated by secretin + CCK
- Exocrine pancreas composed of ducts and acinar cells
Where is secretin produced and what does it do?
- Produced by s-cells of duodenum
- Controls gastric acid secretion + buffering with HCO3-
Where is CCK produced and what does it do?
- Made by I-cells in duodenum
- Responsible for stimulating digestion of fat + protein
- Causes release of digestive enzymes
What is the function of the exocrine pancreas and its secretions?
Function:
- Digestive
- Proteases, lipases + amylase
Secretions:
- Secretes products into ducts (digestive enzymes)
What is the function of the endocrine pancreas and its secretions?
Function:
- Endocrine
Secretions:
- Secrets products into bloodstream (e.g. hormones)
What are the Islets of Langerhans within the endocrine pancreas and what are their features?
Α cells:
- Glucagon increases blood glucose
Β cells:
- Insulin decreases blood glucose
Delta cells:
- Somatostatin regulates Α + Β cells
D1:
- Vasoactive peptide
- Stimulates secretion of H20 into pancreatic system
PP:
- Pancreatic polypeptide
- Self regulates secretion activities
What is a metabolic syndrome and its features?
Collection of conditions that increase risk of IHD
- Fasting hyperglycaemia >6mmol/L
- BP >140/90
- Central obesity
- Dyslipidaemia (decreased HDL cholesterol + increased TGs)
- Microalbuminaemia
How is diabetes mellitus diagnosed?
- Fasting glucose >7mmol/L
OR - Random plasma glucose >11.1mmol/L
OR
HBA1c >48mmol/L
What is the pathogenesis of T1DM and some features?
- Autoimmune destruction of β cells by CD4+ + CD8+ T lymphocytes
- May present with DKA
- Insulin dependent
What is T2DM strongly related to?
- Obesity
- Insulin resistance
What are some macrovascular complications of diabetes?
- Cardiac (IHD)
- PVD (Claudication, change in colour/temp, poor healing ulcers)
- Cerebral (CVA)
What are some microvascular complications of diabetes?
- Glomerulonephritis (renal)
- Ulcers (peripheral neuropathy)
- Diabetic retinopathy (ocular)
How is acute pancreatitis scored?
GLASGOW Scale
- >=3 = severe pancreatitis
What are the causes of acute pancreatitis?
I GET SMASHED
- I: Idiopathic
- G: Gallstones
- E: Ethanol
- T: Trauma
- S: Steroids
- M: Mumps
- A: Autoimmune
- S: Scorpion venom
- H: Hyperlipidaemia
- E: ERCP
- D: Drugs (e.g. thiazides)
What are the most common causes of acute pancreatitis?
- Gallstones
- Ethanol
How does acute pancreatitis present?
- Severe epigastric (central) pain radiating to back
- Pain relieved by sitting forward
- Vomiting prominent
What is seen on blood tests for acute pancreatitis?
- Amylase transiently increase
- Serum lipase big increase (more sensitive)
What are some complications of acute pancreatitis?
- Formation of pseudocyst (pathological collection of fluid)
- Shock
- Hypoglycaemia
- Hypocalcaemia
What is seen on histology for acute pancreatitis?
Coagulative necrosis
What is the pattern of damage in acute pancreatitis?
Periductal damage: is necrosis of acinar cells near ducts, leading to obstructive causes
Perilobular damage: is necrosis at the edge of th elobules leading to ischaemic causes
Panlobular damage: is a combination of periductal and perilobular damage
What are some causes of chronic pancreatitis and which is most common?
- Alcoholism (most common)
- Cystic fibrosis
- Hereditary
- Pancreatic duct obstruction (e.g. stones/tumour)
- Autoimmune (IgG4 produced by plasma cells)
How does chronic pancreatitis present?
- Epigastric pain radiating to back
- Malabsorption (weight loss + steatorrhoea)
- Secondary DM (malabsorption due to lack of enzymes to digest food)
What is seen on histology of chronic pancreatitis?
- Fibrosis
- Loss of exocrine tissue parenchyma
- Duct dilatation with thick secretions
- Calcification
- Similar to pancreatic cancer
What are some complications of chronic pancreatitis?
- Pseudocysts
- Diabetes
- Pancreatic cancer
What are some features of acinar cell carcinoma?
- Rare
- Older adults
- Enzyme production by neoplastic cells
How does acinar cell carcinoma present?
- Non-specific Sx
- Abdo pain
- Weight loss
- Nausea
- Diarrhoea
- ?multifocal fat necrosis + polyarthralgia due to lipase secretion
What is the histopathology of acinar cell carcinoma?
- Neoplastic epithelial cells with eosinophilic granular cytoplasm
- +ve immunoreactivity for lipase, trypsin + chymotrypsin
What is the prognosis of acinar cell carcinoma?
- Median survival = 18mths from diagnosis
- 5-yr survival <10%
What are some RFs for developing gallstones?
- Increasing age
- F>M
- OCP
- Disorders of bile metabolism
What are common forms of gallstones?
- Cholesterol (radiolucent)
- Calcium salts - rarer (radio-opaque)
What is cholelithiasis?
Presence of gallstones in gallbladder (20% adults in West)
What is acute cholecystitis?
- Acute inflammation
- 90% associated with gallstones
What is chronic cholecystitis?
Chronic inflammatino leading to fibrosis (90% a/w gallstones)
What is cholangiocarcinoma?
An adenocarcinoma, 90% a/w gallstones
What is pancreatic carcinoma?
A ductal adenocarcinoma of the pancreas
What is the epidemiology of pancreatic carcinoma?
- 85% of all pancreatic malignancies
- Average age 60yrs
- M>F
Where is pancreatic carcinoma commonly found?
- Normally head of pancreas
What are some RFs for pancreatic carcinoma?
- Smoking
- Diet
- Genetic (FAP, HNPCC)
What are some clinical features of pancreatic carcinoma?
- Weight loss + anorexia
- Upper abdo pain + back pain (chronic, persistent, severe)
- Jaundice (painless), pruritis, steatorrhoea
- DM
- Trousseau’s sign
- Ascites
- Abdominal masses
- Virchow’s node
- Courvoisier’s sign
What are some investigation findings for pancreatic carcinoma?
Bloods:
- Decreased Hb
- Increased bilirubin
- Increased Ca
CT/MR/ERCP
CA19.9 >70IU/mL
What is the management for pancreatic carcinoma?
- Palliative chemotherapy (5-FU)
- Surgery = Whipple’s procedure (surgical resection)
What is the prognosis for pancreatic carcinoma?
Very poor
- 5yr survival rate <5%
Where are neuroendocrine (islet cell) tumours found?
Normally body or tail of pancreas
What are some features of neuroendocrine (islet cell) tumours?
- Circumscribed 1-5cm
- Cells arranged in nests or trabeculae with granular cytoplasm
- May be MEN 1 pts
- May be multiple lesions
- Unpredictable behaviour
What are the functional neuroendocrine tumours and how do they present?
Present: Sx related to hormone excess
- Insulinoma: hypoglycaemic attacks
- Gastrinoma: Zollinger-Ellison syndrome (recurrent ulceration)
- Glucagonoma: Necrolytic migrating erythema
- VIPoma: diarrhoea
When are non-functional neuroendocrine tumours found?
Incidentally on imaging
OR
Grow large enough to produce Sx of local disease or metastasis
What are some investigations for neuroendocrine tumours?
- CT/MRI
- Chromogranin = acts as marker
What is the management for neuroendocrine tumours?
- Surgery
What is Multiple Endrocrine Neoplasia?
A group of genetic syndromes where there are functioning hormone-producing tumours in multiple organs
What are some pancreatic malformations?
- Ectopic pancreas
- Pancreas divisum (failure of fusion of dorsal + ventral buds = increased risk of pancreatitis)
- Annular pancreas (presents with duodenal obstruction)
