Histo: Diseases of the Pancreas and Gallbladder Flashcards
Outline the pancreatic microanatomy
Main pancreatic duct drains into the common bile duct.
Intercalated ducts branch from pancreatic duct and drain in Pancreatic Acini (composed of pancreatic acini cells which contian multiple granules containing digestive enzymes - these are released into the intracelated ducts).
Around the Pancreatic Acini group of cells, are little islands of cells NOT connected to intercalated ducts. These are called Islets of Langerhaans and are composed of alpha cells (glucagon), Beta cells (insulin) and Delta cells (somatostatin).
Define acute pancreatitis.
Acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes which become activated within the pancreas causing inflammation and destruction.
List some causes of acute pancreatitis.
Duct Obstruction
- Gallstones (80%)
- Tumours
- Trauma
Metabolic / Toxic
- Alcohol
- Drugs (Thiazides)
- Hypercalcaemia
- Hyperlipidaemia
Poor blood supply
- Shock
- Hypovolaemia
Infection/Inflammaiton
- Mumps (infects the acini cells directly)
Autoimmune
Idiopathic
What are the 2 main Pathogenesis mechanisms of Acute Pancreatitis
Obstruction of release of pancreatic fluid > causes stasis of pancreatic pro-enzymes which causes their activaiton > causes damage to acini cells and their ultimate necrosis > necrosis of acinar cells causes further release of pancreatic enzymes
Direct acinar injury
Describe how alcohol can cause acute pancreatitis.
Does so in 2 ways:
1. It leads to spasm/oedema of the sphincter of Oddi which obstructs the release of pancreatic fluid
2. Formation of protein-rich pancreatic fluid which is thick and sludges ultimately causing an obstruction
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 - combinaiton of both periductal and perilobular (results from worsening periductal or perilobular inflammation)
Outline how fat necrosis occurs in acute pancreatitis and how this impacts calcium levels in blood.
Pathogenesis of Fat Necrosis
- Aberrant release of activated lipases causes the breakdown of triglycerides into glycerol and FFAs
- FFAs in blood bind to free Ca2+ causing soapinificaiton (yellow/white foci which can be seen when a pancreas is opened in surgery)
Impact on calcium levels in blood
- Calcium levels can decrease as more and more FFAs are found in blood due to aberrant lipase release from acute pancreatitis.
- HOWEVER MUST REMEMBER - a cause of acute pancreatitis is hypercalcaemia - so actually fat necrosis can bring levels of Ca2’ into the normal range in these patients!
List some complications of acute pancreatitis.
- Pseudocyst formation, abscesses
- Shock (haemorrhagic pancreatitis = very severe!!)
- Hypoglycaemia (due to damage extending from acinar cells into islets of langerhaans)
- Hypocalcaemia (due to fat necrosis!)
Define pseudocyst.
- A collection of fluid (pancreatic juices) 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
This is NOT an abscess because abscess is collection of PUS!
Define chronic pancreatitis and what differentiates it from acute
Relapsing or persistent inflammation of pancreas - associated with acute pancreatitis.
Presence of fibrosis (replacing parenchyma) = what differentiates it from acute pancreatitis
List some causes of chronic pancreatitis.
- Metabolic/Toxic: alcohol (80%), haemochromatosis
- Duct obstruction: gallstones, abnormal anatomy, cystic fibrosis (mucoviscoidosis)
- Tumours
- Acute/Idiopathic
Outline the pattern of injury in chronic pancreatitis seen in histology!
- Chronic inflammation with parenchymal fibrosis and loss of parenchyma
- There will be duct strictures with calcified stones (can be seen on X-RAY!) 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
List the different types of pancreatic neoplasms
Carcinomas:
- Ductal (85% - commonest pancreatic cancer)
- Acinar
Cystic Neoplasms (benign)
- Serous cystadenoma
- Mucinous cystic neoplasm
Neuroendocrine Tumours (Islet cell tumours)
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 and state which genetic mutation commonly predisposes patients to them.
- Pancreatic intraductal neoplasia (PanIN)
- Intraductal mucinous papillary neoplasm
Genetic mutation = 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 (increased synthesis of extracellular matrix proteins and collagen by stromal cells)
What is the most common site of ductal carcinoma?
Head (60%)
NOTE: neuroendocrine tumours are more common in the tail
What tumour marker can be used for pancreatic ductal carcinoma
CA 19.9
What are the usual sites of metastasis of ductal carcinoma?
- Direct: bile ducts, duodenum
- Lymph nodes
- Blood: liver
- Serosa: peritoneum
NOTE = Commonest method of invasion is perineural
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 (3) of pancreatic neuroendocrine neoplasms.
- Usually non-secretory
- Contains granules which store chromogranin (this is crucial as can be measured in serum as neuroendocrine marker or stained in histology)
- May be associated with MEN1
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
- > 50% cholesterol composed
- 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
Gallstones is commonly associated with ALL gallbladder pathology!
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. Common in chronic cholecystitis
Differentiate between acute and chronic cholecystitis
Chronic cholecystits gallbladder has fibrosis! Making it thicker and harder. It also contains calcification.
Which type of cancer is gallbladder cancer?
Adenocarcinoma
NOTE: it is technically a type of cholangiocarcinoma