Histopath - Pancreas and gall bladder Flashcards
What is the histology of the pancreas
Exocrine: ducts and ascini, protease, amylase, lipase
Endocrine: islets of langerhans for glucagon, insulin and somatostatin
Define acute pancreatitis
Acute inflammation caused by aberrant release of pancreatic enzymes
What are the causes of acute pancreatitis
(Idiopathic 15%)
Gallstones (50%)
Ethanol (33%)
Steroids
Mumps
Autoimmune
Scorpion bite
Hyper-calcaemia/-lipidaemia
ERCP
Drugs (thiazides)
Duct obstruction: gallstones, trauma, tumours
Metabolic/toxic: alcohol, drugs, hypercalcaemia, hyperlipidaemia
Poor blood supply : shock, hypothermia
Infection/inflammation: viruses e.g. mumps
What is the role of calcium in acute pancreatitis
Can be a be a cause (hypercalcaemia)
Also CAUSES hypocalcaemia
Lipases released → fat necrosis → FFAs → binds the free calcium → reduced free calcium (saponification) → yellow-white foci; so, if this is the cause, calcium drops to a NORMAL level in the acute phase
What is the pathogenesis of acute pancreatitis
Duct obstruction: gallstones become stuck distal to the the connection between the common bile duct and pancreatic duct → reflux of bile up the pancreatic duct → release of pro-enzymes → activated → damage to the acini
Alcohol → spasms/oedema of the sphincter of Oddi and formation of protein-rich pancreatic fluid → duct obstruction
Ranges from stromal oedema to haemorrhagic necrosis
Direct acinar injury
What are the patterns of injury in acute pancreatitis
peri-ductal: necrosis of acinar cells near the ducts (usually secondary to obstruction)
Peri-lobular: necrosis at the edges of the lobules (usually due to poor blood supply)
Pan-lobular: this will develop from worsening of either periductal or perilobular inflammation
What are the complications of acute pancreatitis
Pancreatic: pseudocyst formation (collection of fluid without epithelial lining) → infection → abscess
Systemic: shock, hypoglycaemia, hypocalcaemia
What is the prognosis for acute pancreatitis
Dependent on severity
Mortality of 50% for haemorrhagic pancreatitis
What are the histological features of acute pancreatitis
Macroscopically: Yellow nodules (foci fat necrosis)
Microscopically: blue areas = calcium, coagulative necrosis
What are the features of chronic pancreatitis
Relapsing or persistent
Associated with acute pancreatitis in about half of cases (scarring)
Relatively uncommon
Mortality of 3% per year
What are the causes of chronic pancreatitis
Metabolic/toxic: ALCOHOL, haemochromatosis
Duct obstruction: gallstones, abnormal pancreatic duct anatomy, cystic fibrosis “mucoviscoidiosis”
Tumours
Idiopathic: autoimmune
Pathogenesis is the same as acute pancreatitis
What are the patterns of injury in chronic pancreatitis
Chronic inflammation with parenchymal fibrosis and loss of parenchyma (ascini become atrophic)
Duct strictures with calcified stones with secondary dilatations (calcification = diagnostic of chronic pancreatitis)
What are the complications of chronic pancreatitis
EARLY: Malabsorption (occurs much earlier as lipases, etc. are not produced)
LATE: Diabetes mellitus (late stage as endocrine parts survive much longer than exocrine components)
Pseudocysts
Carcinoma of the pancreas (?)
What is the histology of chronic pancreatitis
Macro: scarring, pale tissue, cyst formation
Micro: Fibosis (pale pink), islets behind. Acini atrophy → depletion, calcification, duct dilatation with thick secretions
What are pancreatic pseudocysts and its histology
Associated with acute and chronic pancreatitis → pseudocyts → resolution, perforation, compression of adjacent structures, infection
Lined by fibrous tissue (no epithelial lining)
Contains fluid (rich in pancreatic enzymes or necrotic material)
Connects with pancreatic ducts
What is IgG4 related disease of the pancreas
Autoimmune pancreatitis
Large numbers of IgG4 +ve plasma cells
May involve the pancreas, bile ducts and almost any other part of the body
Duct is surrounded by loads of IgG4 expressing plasma cells
These patients respond very well to steroids
What are the tumours of the pancreas
Carcinoma (85%):
- Ductal (5% of deaths)
- Acinar → Acinar-ductal metaplasia
Cystic neoplasms
- Serous cystadenoma
- Mucinous cystic neoplasm
Pancreatic neuroendocrine tumours (islet cell tumours)
What are the risk factors for pancreatic cancer
Smoking
BMI and dietary factors
Chronic pancreatitis
Diabetes mellitus
Describe ductal carcinomas of the pancreas (epidemiology, aetiology, prognosis)
Increasingly common with age; M>F (2: 1)
Pre-malignant bridges that do NOT invade through the BM:
- Pancreatic intraductal neoplasia (PanIN)
- Intraductal Mucinous papillary neoplasm
95% k-ras mutation
5-year survival = 5%
Describe the histology of pancreatic ductal carcinomas
Macroscopic:
- Gritty and grey
- Invasion of adjacent structures
- Head (60%), body, tail, diffuse
Microscopic:
- Adenocarcinomas: mucin secretion, gland formation, desmoplastic stroma (tumour induces fibrous tissue growth around it)
- Perineural invasion
How do ductal carcinomas of the pancreas spread
DIRECT: bile ducts, duodenum
LYMPHATIC: lymph nodes
BLOOD: liver
SEROSA: peritoneum
What are the complications of ductal carcinoma of the pancreas
Due to spread
Chronic pancreatitis
Venous thrombosis (migratory thrombophlebitis) – CHARACTERISTIC →Circulating pancreatic cancer cells releasing mucous which activates the clotting cascade
Describe acinar pancreas carcinomas
Acinar-ductal metaplasia - most tumours arise from the acini but appear to arise from the ducts due to acinar-ductal metaplasia
Histology: neoplastic epithelial cells with eosinophilic granular cytoplasm. Positive immunoreactivity for lipase, trypsin and chymotrypsin.
Associated with increased serum lipase → multifocal fat necrosis and polyarthralgia
Describe cystic tumours of the pancreas
Includes serous cystadenomas and mucinous cystic neoplasm
Contain serous or mucin secreting epithelium (like ovarian tumours)
Usually benign
Describe pancreatic endocrine neoplasms
Usually non-secretory
Stained by neuroendocrine markers (Chromogranin)
Includes:
- Insulinomas (beta cell)
- MEN1
tail > body > head
What is Whipple’s triad
Hypoglycaemia
S/S hypoglycaeima
Relief of symptom of administration of glucose
What are the risk factors for gallstones
Female
40yo
Obesity
Ethnicity (e.g. Native Americans) - 20% of the West have gallstones
Hereditary factors (e.g. disorders of bile metabolism)
Drugs (e.g. oral contraceptive)
Acquired disorders (e.g. rapid weight loss)
What are the types of gallstone and what is their appearance on AXR
Cholesterol (>50%): single stone, radio-lucent on AXR (US to diagnose)
Pigment (calcium salts of unconjugated bilirubin): multiple, radio-opaque (contains Ca)
What are the complications of gallstones
Bile duct obstruction
Acute and chronic cholecystitis
Gallbladder cancer
Pancreatitis
What is the histology of acute cholecystitis
Acute inflammation (neutrophils, oedema)
90% are associated with gallstones
What is the histology of chronic cholecystitis
90% contain gallstones
Fibrosis, small, neoangiogenesis
Diverticula (Rokitansky-Aschoff sinuses) – gallbladder contracting against obstruction → diverticula
Describe pancreatic action
Secretin and CCK → 2L a day of enzymic HCO3- rich fluid
Secretin = gastric-acid secretion and buffering with HCO3-, produced by s-cells of duodenum
CCK = stimulates digestion of fat and protein, produced by i-cells in the duodenum
What are the functions of the pancreas
Exocrine: digestion (protease, lipase, amylase release)
Endocrine: secretion of hormones
- Alpha: glucagon
- Beta: insulin
- Delta: somatostatin (regulation of alpha and beta)
- D1: vasoactive peptide → stimulates H2O secretion
- PP: pancreatic polypeptide, self-regulates secretion activities
What is metabolic syndrome
Collection of conditions that increase risk of IHD
- Fasting hyperglycaemia >6 mmol/l.
- BP >140/90
- Central obesity (>94cm in M, >80cm F)
- Dyslipidemia: Decreased HDL cholesterol <1mmol/l & Increased TGs >2mmol/l
- Microalbuminaemia
How is pancreatitis severity scored
GLASGOW
≥3 = Severe Pancreatitis
What is the difference between cholecystitis, cholelithiasis, and cholangiocarcinoma
Cholecystitis = Inflammation of the gall bladder (chronic → inflammation → fibrosis)
Cholelithiasis = Presence of the gallstones in the gall bladder
Cholangiocarcinoma = adenocarcinoma of the gall bladder
What are the types of multiple endocrine neoplasia (MEN)
MEN1:
- Parathyroid hyperplasia/adenoma
- Pancreatic endocrine tumour (often phaeochromocytoma)
- Pituitary adenoma
MEN 2A
- Parathyroid
- Thyroid
- Phaeochromocytoma
MEN 2B
- Medullary Thyroid
- Phaeochromocytoma
- Acoustic Neuroma
- Marfanoid phenotype
What are the pancreatic malformations
Ectopic Pancreas – esp. stomach, small intestine.
Pancreas Divisum – failure of fusion of dorsal and ventral buds, increased risk of pancreatitis.
Annular pancreas – can present with duodenal obstruction approx. 1yo
What are the symptoms and signs of pancreatic ductal adenocarcinoma
Weight loss (cachexia) and anorexia
Upper abdominal and back pain (chronic, persistent and sever)
Jaundice (painless), pruritus, steatorrhoea
DM
Trousseau’s syndrome (25%)- recurrent superficial thrombophlebitis
Ascites
Abdominal mass
Virchow’s node
Courvoisier’s sign
What investigations should be done for ductal adenocarcinoma of the pancreas and what is the management
Bloods: ↓Hb, ↑Bili, ↑Ca2+
CT/MRI/ERCP
CA19.9 >70IU/mL
Mx: Palliative chemo, Whipple’s procedure
