Pancreas and Gallbladder Histopath Flashcards
Functions of the pancreas
Exocrine: production of digestive enzymes
Produces 2L a day of enzymic HCO3- rich fluid, stimulated by secretin and CCK. Exocrine pancreas is composed of ducts and acinar cells
Endocrine production of glucose-regulating hormones such as insulin and glucagon
Structure of the pancreas (micro)
acini made of acing and centroacinar cells secrete into intercalated ducts -> Pancreatic ducts
90% of pancreas is exocrine
Islets of Langerhans scattered through pancreas, made of alpha, beta, delta, epsilon and Pancreatic Polypeptide (PP) cells plus capillaries to secrete the hormones into
Neuroendocrine cells in the pancreas - where are they found?
Islets of Langerhans
Inflammatory diseases of the pancreas
acute pancreatitis
chronic pancreatitis
IgG4 related disease
acute pancreatitis - what causes the damage?
most damage caused by enzymes released by the pancreas
acute inflammation of the pancreas caused by aberrant release of pancreatic enzymes
can cause acute abdomen
Causes of acute pancreatitis
Duct obstruction
- gall stones (50%)
- tumours
- trauma
Metabolic/toxic
-alcohol (33%)
- drugs e.g. thiazides
- hypercalcaemia
- hyperlipidaemia
Poor blood supply
- shock
- hypothermia
Infection/inflammation
- viruses e.g. mumps
Autoimmune
- IgG4 related disease
Idiopathic (15%)
Commonest cause of acute pancreatitis
- gallstones - 50%
- alcohol - 33%
Pathogenesis of acute pancreatitis
- Duct obstruction
Gallstone stuck distal to where the 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 then become activated
Alcohol leads to spasm/oedema of Sphincter of Oddi and the formation of a protein rich pancreatic fluid which obstructs the pancreatic ducts
- Direct acing injury (due to the causes other than obstruction and alcohol, e.g. infectious, inflammatory, shock etc)
Pattern of injury in acute pancreatitis
Periductal - necrosis of acinar cells near ducts (usually secondary to obstruction e.g. gallstones and alcohol)
Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply)
Panlobular – develops from 1. and 2.
distribution of changes can give you hints on pathogenesis
Activated enzymes -> acinar necrosis -> enzyme release etc.
Ranges from stromal oedema, to haemorrhagic necrosis
e.g. Lipases -> fat necrosis (calcium ions bind to free fatty acids forming soaps which are seen as yellow-white foci)
Complications and prognosis of acute pancreatitis
pancreatic:
- pseudocyst
- abscess
systemic
- shock
- hypoglycaemia
- hypocalcaemia (because Ca combines with fatty acids to produce fatty necrosis)
- ARDS
Prognosis: overall mortality up to 50% for haemorrhagic pancreatitis
What is the prognosis of acute pancreatitis
overall mortality up to 50% for haaemorrhagic pancreatitis
if you only haave mild oedema you should be okay
Chronic pancreatitis - stats
relatively uncommon
mortality 3%/yr
relapsing, persistent, associated with acute pancreatitis in 50% cases
causes of chronic pancreatitis
Metabolic/toxic
- alcohol (80%)
- haemochromatosis (because iron can be deposited in the pancreas)
Duct obstruction
- gallstones
- abnormal pancreatic duct anatomy
- CF (chronic disease -> chronic pancreatitis)
Tumours
Idiopathic (autoimmune)
Pathogenesis of chronic pancreatitis
as for acute pancreatitis, e.g. acinar damage by digestive enzymes and necrosis
Chronic inflammation with parenchymal fibrosis and loss of parenchyma
Duct strictures with calcified stones with secondary dilatations
Complications of chronic pancretaitis
DM (late)
malabsorption
pseudocysts
?carcinoma of the pancreas (not sure yet, chicken and egg situation)
X-ray spot diagnosis of chronic pancreatitis
white foci in the pancreas area
calcifications
histopath chronic pancreatitis
fibrosis (pale pink) and loss of exocrine tissue parenchyma (acini disappear, the neuroendocrine tissue is still there mostly. sometimes this can make histopathologists question if this is chronic pancreatitis or a neuroendocrine tumour)
duct dilatation with thick secretions
calcification
lymphocytes
Pancreatic pseuodocyst
- lined by fibrous tissue (not epithelial!!) - do not have a capsule
- associated with acute and chronic pancreatitis
- contain fluid rich in pancreatic enzymes or necrotic material
- connect with pancreatic ducts
- may resolve, compress adjacent structures, become infected or perforate
IgG 4 related disease
characterised by large number of IgG4 positive plasma cells
may involve the pancreas, gallbladder, bile ducts and any other part of the body…..
-> can cause autoimmune pancreatitis
histology shows: lots of plasma cells
IgG immunohistochemistry: brown stained cells
important ddx for e.g. pancreatic cancer and other pancreatic diseases
managed with steroids, just melts away
histology of IgG4 related diseases (pancreas)
- ddx of pancreatic caancer
- IgG4 positive plasma cells on histopath
How do you manage IgG4 related diseases?
responds well to steroids
categories of pancreatic tumours
carcinomas (ductal, acinar)
cystic neoplasms (serous cysstadenoma, mutinous cystic neoplasm)
pancreatic neuroendocrine tumours (islet cell tumours)
What are the comments cancer of the pancreas?
Ductal carcinomas (85%)
types of pancreatic carcinomas
ductal (85% of all pancreatic neoplasms)
acinar
types of cystic neoplasms in the pancraas
serous cyst adenoma
mutinous cystic neoplasm
5 yr survival of ductal carcinoma (pancreas) and stats
5%
increasingly common with age
2M : 1F
Risk factors for pancreatic carcinoma
smoking
BMI and dietary factors
chronic pancreatitis
diabetes
Pre-existing lesion in pancreas leading to pancreatic ductal carcinoma
Ductal carcinoma arises from dysplastic duc tal lesions:
- PanIN (pancreatic intraductal neoplasm)
- IMP (Intraductal Mucinous Papillary neoplasm )
Kras mutation in 95% cases
What mutation is common in Pre-existing lesion in pancreas leading to pancreatic ductal carcinoma
Kras mutation in 95%
Why do some pancreatic tumours present earlier based on their location?
tumours in the head present earlier than e.g. in the tail because they cause sooner obstructive symptoms
if in the tail etc. usually only present with mets to e.g. liver
Macroscopic ductal carcinoma of pancreas
- Gritty and grey
- Invades adjacent structures
- Tumours in the head present earlier
- hard because
Microscopic features of ductal carcinoma of pancreas
Adenocarcinomas:
mucin secreting glands set in desmoplastic stroma
-> secrete mucin
-> form glands
(this is true of any adenocarcinomas)
How do pancreatic carcinomas spread
direct -> duodenum, bile ducts
blood -> liver
lymphatics -> lymph nodes
serosa -> peritoneum
perineural spread if perineurial invasion (very characteristic)
areas of pancreatic carcinoma
Head 60%
body
tail
diffuse
complications of pancreatic ductal carcinoma
- due to spread/metastases
- chronic pancreatitis
- venous thrombosis (migratory thrombophlebitis)
cystic tumours of pancreas
- contain serous or mucin secreting epithelium (cf. ovarian tumours)
- usually benign (mainly adenomas, rarely adenocarcinomas)
Pancreatic endocrine neoplasms
- usually non-secretory
- contain neuroendocrine markers e.g. chromogranin
- behaviour is difficult to predict
- may be associated with MEN 1
what is a neuroendocrine marker?
chromogranin (Can be detected In e.g. pancreatic neuroendocrine neoplasms)
Commonest neuroendocrine tumour of pancreas
insulinoma (derived from beta cells)
stains for chromogranin
b-cells affected, secrete insulin
commonest type of secretory tumour
How common are gallstones
20% adults in west have them
commoner in women
increasing age
common in native Americans
What medications are RF for gallstones
oral contraceptives
RFs for gall stones
increasing age
F >M
ethnic and geographic factors (e.g. native Americans)
hereditary (e.f. disorders of bile metabolism)
drugs (e.g. oral contraceptive)
acquired disorders (e.g. rapid weight loss)
Different types of gallstones
cholesterol (must contain more than 50% cholesterol, mainly single and radiolucent)
pigment (contain calcium salts of unconjugated bilirubin, multiple, mostly radio-opaque, small)
What gallstoness are not seen on xray?
cholesterol because hey are mostly single radiolucent
What gallstoness are seen on xray and why?
pigment
because they contain calcium and are radio-opaque
usually small and multiple
Complications of gall stones
bile duct obstruction
acute and chronic cholecystitis
gall bladder cancer
pancreatitis
Acute cholecystitis
acute inflammation (neutrophil polymorphs)
90% associated with gallstones
causes of acute no stones cholecystitis
salmonella, typhoid
chronic cholecystitis
chronic inflammation (lymphocytes, neutrophils)
FIBROSIS - key for chronic
diverticula - Rokitasky-Aschoff sinuses
90% contain fall stones
thick gallbladder wall due to fibrosis
What % of poeple with chronic cholecystitis have gallstones?
90%
Rokitansky Aschoff sinuses
- diverticula seen in chronic cholecystitis
- mucosa pushed out into the wall by raised intralminal pressure
- out pocketing of mucosa
Gall bladder cancer
adenocarcinomas
90% associated with gallstones
Which is the commonest type of pancreatic neoplasm?
ductal adenocarcinomas
Which of the following most rarely causes chronic pancreatitis?
- alcohol
- gallstones
- CF
gallstones (are a very rare cause)
The following are all complications of gall stone except
- acute cholecystitis
- gall bladder cancer
- haemolytic anaemia
- obstructive jaundice
- haemolytic anaemia is not a complication of gall stones
HA is itself a cause of gallstones
Acute pancreatitis - how does duct obstruction cause damage?
Gallstones:
-> gallstone stuck distal to where the common bile and pancreatic ducts join
-> reflux of bile up the pancreatic duct
-> damage to the acini and release of proenzymes which become activated
Alcohol:
-> spasm/oedema of sphincter of Oddi
-> formation of a protein-rich pancreatic fluid which obstructs the pancreatic duct
Name a neuroendocrine marker
chromogranin
What is chromogranin?
A neuroendocrine marker
Where is the pancreas located
in the retroperitoneum (secondarily retroperitoneal)
posterior to the stomach
between the duodenal curvature and the splenic hilum
Gross anatomy of pancrease
head
uncinate process
neck
body
tail
Where does the pancreas receive blood supply from and why?
from the coeliac trunk and its branches
because it is derived from the foregut
Ducts in the pancreas
pancreatic duct begins in the tail
travels towards the head
then runs inferiorly
then joins the bile duct and forms the hepatopancreatic ampulla (Ampulla of Vater)
this enters the descending duodenum and the major duodenal papilla which is surrounded by the sphincter of Oddi
What is the sphincter of Oddi
a collection of smooth muscles surrounding the ampulla of Vater
controls the secretion of bile and pancreatic fluid into the duodenum
How many pancreatic ducts empty into the duodenum and how?
2
pancreatic duct after joining with the bike duct and forming the ampulla of Vater which empties into the descending duodenum via the major duodenal papilla
accessory pancreatic duct empties into the duodenum at the minor duodenal papilla, just above the major one
hormones produced by the pancreas
glucagon
insulin
somatostatin
vertebral level - pancreas
L1/L2
Courvoisier sign
tumours in the pancreatic head often cause bile duct obstruction and can manifest with painless janudice
How does the pancreas look like on histopath?
acini: small groups of cells making ‘circles’ that are pink on the inside and purple on the outside
islets of Langerhans: less dense
there may be big white bubbles which are adipocytes
Where are secretin and CCK produced and what do they cause?
Secretin: produced by s-cells of the duodenum, controls gastric acid secretion and buffering with HCO3-
CCK: responsible for stimulating digestion of fat and protein. Made by I-cells in the duodenum. Causes release of digestive enzymes.
Cells in the islets of largerhans and what they secrete
Alpha cells: glucagon increases blood glucose
Beta cells: insulin decreases blood glucose
Delta cells: somatostatin regulates the above cells
D1: a vasoactive peptide, stimulates the secretion of H20 into pancreatic system PP: pancreatic polypeptide, self regulates secretion activities
What is metabolic syndrome and what are the components?
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
diagnostic criteria for diabetes mellitus
Fasting plasma glucose >7 mmol/L
OR
random plasma glucose >11.1 mmol/L
OR
HBA1c >48 mmol/L.
Scoring criteria for acute pancreatitis and when is it severe
GLASCOW scale
> or = 3 is severe
causes of acute pancreatitis acronym
‘I GET SMASHED’:
Idiopathic (15%)
Gallstones (50%)
Ethanol (33%)
Trauma
Steroids
Mumps
Autoimmune
Scorpion venom
Hyperlipidaemia
ERCP
Drugs e.g. thiazides
presentation of acute pancreatitis (incl blood markers)
severe epigastric (or central) pain radiating to back, relieved by sitting forward, vomiting prominent
Amylase only transiently increased. Serum lipase is more sensitive.
acute pancreatitis histology
coagulative necrosis
acute pancreatitis - causes of damage based on pattern of injury
Periductal → necrosis of acinar cells near ducts → obstructive causes.
Perilobular → necrosis at edge of lobules → ischaemic causes.
Panlobular → combination of both.
fat necrosis in the pancreas - how does it occur?
lupines???? produce fat necrosis
calcium and fatty acid precipitates cause fat necrosis
“digestive enzymes react with visceral fat causing precipitation of calcium soaps (fat necrosis).” - meted
lining of pancreatic pseudocyst
fibrous tissue (NOT epithelial)
therefore PSEUDOcyst
What % alcoholics get acute pancreatitis?
5%
Why is IgG4 related disease important in the context of the pancreas?
it is an important differential diagnosis for e.g. pancreatic cancer and can be managed simply with steroids which cause the disease to melt away in the pancreas
what % of cancer deaths is due to ductal carcinoma of the pancreas?
5% of cancer deaths
Why are pancreatic cancers hard?
because of desmostronal
Insulinoma
derived form pancreatic beta cells
stains for chromogranin
commonest type of secretly tumour
MEN - what are they and what types are theere
A group of genetic syndromes where there are functioning hormone-producing tumours in multiple organs e.g;
- MEN 1= ‘PPP’ - 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 different types of gallbladder disease?
gallstones
inflammation
cancer
Types of 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 different types of pancreatic neuroendocrine tumours
- Functional – present with Sx related to hormone excess
o Insulinoma – hypoglycaemic attacks(most common)
o Gastrinoma – Zollinger-Ellison syndrome (high acid output):recurrent ulceration o Otherse.g.VIPoma–diarrhoea
o Glucagonoma–necrolytic-migrating erythema - Non-functional – picked up incidentally on imaging or when grow large enough to produce symptoms of local disease or metastasis
