Histopathology 9: Pancreatic pathology Flashcards
Which 2 mediators control enzyme and alkali release from the pancreas ?
Secretin - released by S cells in the duodenum causes pancreatic HCO3- secretion
CCK- released by I cells in the duodenum causes pancreatic release of digestive enzymes
Which cells release glucagon and insulin?
Glucagon = alpha cells
Insulin = beta cells
Which cells release somatostatin ?
Delta cells
What type of hypersensitivity reaction is T1DM ?
Type 4 delayed T cell mediated
List the causes of Acute pancreatitis ?
I GET SMASHED
Idiopathic (15%)
Gall stones (50%)
Ethanol (35%)
Trauma
Steroids
Mumps
Auto-immune
Scorpion venom
Hyperlipidaemia
ERCP
Drugs- Thiazide diuretics, allopurinol
Which blood test is most sensitive for Acute pancreatitis ?
Serum Lipase
List 5 causes of chronic pancreatitis ?
- Alcoholism (80%)
- Cystic fibrosis - mucoviscoidosis (Mucus overproduction causing duct obstruction)
- Haemochromatosis (‘Bronzed diabetes’)
- Pancreatic duct obstruction - stones /cancer (less important)
- Auto-immune
Describe the histology of chronic pancreatitis ?
- Dilated ducts with strictures
- Fibrosis and fat
- Calcification (calcium stones form)
- Loss of exocrine tissue (acini) which are replaced by fibrous tissue
A patient presents with significant weight loss, abdominal pain, multifocal fat necrosis and polyarthralgia.
Histopathology: Eosinophilic granular cytoplasm, immune reactivity for lipase
Most likely diagnosis ?
Acinar cell carcinoma
neoplasm that releases lots of lipase
A patient presents with epigastric pain that radiates to the back, he’s jaundiced and appears cachectic. An abdominal mass is felt on examination.
Most likely diagnosis ?
Ductal adenocarcinoma of the pancreas
Where in the pancreas do Ductal adenocarcinomas tend to occur ?
Head of the pancreas (60%)
what is courvoisiers law?
Presence of a palpable enlarged gallbladder, with painless jaundice means gallstones are unlikely, more likely cancer
What is the tumour marker for pancreatic/ductal cancer ?
CA19-9
Histopathology: Cells arranged in nests or trabecular with granular cytoplasm.
Hypoglycaemic attacks.
Most likely diagnosis ?
Islet cell tumour- Insulinoma
Which syndrome is associated with gastrinomas
Zollinger ellison syndrome
What are Rokitansky-Aschoff sinuses ?
- Cholecystitis causes fibrosis which means the gallbladder is contracting against an obstruction
- This pressure causes diverticula to form which are known as Rokitansky-Aschoff sinuses
- So a result of chronic cholecystitis
what are the 2 components of the exocrine parts of the pancreas
ductal
acinar - where enzymes are made
describe how duct obstruction causes acute pancreatitis
gallstone distal to where common bile duct and pancreatic ducts join leads to reflux of bile up the pancreatic duct followed by damage to acini and release of proenzymes which become activated
NB alcohol also cause obstruction as it leads to spasm of Sphincter of Oddi
All other pancreatitis causes = direct injury to acinar cells (drugs, scorpioon venom etc)
describe different patterns of injury in acute pancreatitis
- periductal - necrosis of acinar cells near the ducts (usually secondary to obstruction)
- perilobular - necrosis at the edges of the lobules (usually due to poor blood supply)
- panlobular - develops from worsening of periductal or perilobular inflammation (VERY SEVERE)
pathway of inflammation in acute pancreatitis
activated enzymes > acinar necrosis > bile and enzyme release (then get positive feedback loop)
what are complications of acute pancreatitis
- pancreatic pseudocysts formation
- abscess
- systemic - shock, hypoglycaemia, hypocalcemia
list complications of chronic pancreatitis (4)
- malabsorption
- DM
- pseudocysts (lined by fibrous tissue, contains fluid risk in pancreatic enzymes or necrotic material)
- carcinoma of the pancreas
describe features of AI pancreatitis
- IgG4 related disease
- large numbers of IgG4 positive plasma cells
- responds well to steroids
What happens to calcium levels in acute pancreatitis, and what is this called?
- lipase release will hydrolyse fatty acids from triglycerides
- Calcium ions bind to FFAs forming soaps (which are seen as yellow-white foci)- this is SAPONIFICATION
- These complexes will deposit in tissues. This produces white flecks of FFA + calcium
- This is why pancreatitic patients have low blood calcium as calcium has been sequestered in the process of fat necrosis
Mortality in haemorrhagic/ necrotic pancreatitis
mortality up to 50%
Why is AXR useful in chronic pancreatitis?
Get calcium deposits in pancreas (saponification), which shows up as stones
Most common site for carcinoma in pancreas
Ductal (85%)
Other: acinar
Features of ductal carcinoma
- classic cancer: weight loss
- Courvoisier’s law: palpable gallblader with PAINLESS jaundice
- Can also get abdo pain, pruritis, diabetes mellitus
RF for pancreatic carcinoma
- Smoking
- BMI and dietary factors
- Chronic pancreatitis
- Diabetes mellitus- carry increased risk (very low)
Type of cancer in gallbladder cancers
What are 90% cases associated with?
adenocarcinomas
90% = gallstones
What is chronic Cholecystitis and what are 90% of cases associated with?
- Chronic inflammation with fibrosis, causing Gallbladder with thick wall
- Get Rokitansky-Aschoff sinuses (basically diverticulae due to gallbladder contracting against an obstruction)
- 90% = gallstones (also the case for acute cholecystitis)
Most common type of secretory tumour
Insulinoma (secrete insulin from beta-cells)
Causes hypoglycaemia attacks
5 F’s for gallstone causes
fair (Caucasians), fat (BMI ≥ 30), forty (+ years), female, fertile (≥ 1 children)
2 types of gallstones
- cholesterol (> 50%)
- Pigment stones - contain calcium salts of unconjugated bilirubin
What blood effect will ductal carcinoma of pancreas cause?
Venous Thrombosis - Tumours are often bulky and secrete mucin into the blood stream, activating the clotting cascade and producing thrombi in various places in the body
Mutation in 95% cases of ductal carcinoma
K-RAS mutations
2 pre-invasive stages of pancreatic cancer
- Pancreatic Intraductal Neoplasia
- Intraductal Mucinous Papillary Neoplasm
Most common site in pncreas of Neuroendocrine tumours
Tail of pancreas
Neuroendocrine marker in Pancreatic neuroendocrine Neoplasms
What syndrome may they be associated with?
chromogranin
MEN1
