Pancreas Pathology Flashcards
what are the causes of acute pancreatitis? (GET SMASHED)
- Gallstones
- Ethanol
- Trauma – post op
- Steroids
- Mumps = Infection – also CMV, coxsackie
- Autoimmune
- Scorpion bites
- Hypercalcaemia, hypothermia, hyperlipidaemia
- ERCP
- Drugs = sodium valproate, azathioprine
what is the pathophysiology of acute pancreatitis?
Sudden inflammation and haemorrhaging of the pancreatitis due to destruction by its own digestive enzymes – autodigestion
what role does acinar cells play in pancreatitis?
if inactive proenzyme or zymogen is activated early can cause damage to pancreas (eats itself?)
how can alcohol cause pancreatitis?
- increase zymogen production by altering membrane causing early activation
- secretion decreases fluid and bicarbonate production in ducts causing pancreatic juices to become thick,
causes blockage, build up, distension - stimulate immune response in acinar cells
how can gallstones cause pancreatitis?
gallstone can occur at sphincter of odi causing pancreatic blockage
leads to build up, enzyme activation and distension
What are the clinical symptoms of acute pancreatitis?
- Upper abdominal pain - begins in epigastrium, become intensity as spreads in peritoneal cavity, back pain
- Nausea/vomiting
- Tachycardia, hypotension, oliguric
- Tenderness, guarding
- Reduced/absent bowel sounds
what are the clinical signs of acute pancreatitis?
- Cullen’s Sign – periumbilical bruising
* Grey Turner sign – flank bruising
how does Duodenopancreatic reflux cause pancreatitis?
trauma, surgery, duodenal fluid contains enterokinase that activates pancreatic proenzymes
what causes pancreatic tissue destruction in acute pancreatitis?
from proteases & inflammatory response of the body – raised intracellular calcium can cause this activation
what follows pancreatic tissue destruction in acute pancreatitis pathophysiology?
- Blood vessels become leaky and rupture y proteases digesting the walls of the blood vessel – amylase is released
- edema causes capsule of pancrease to swell
what causes skin discolouration in acute pancreatitis?
• lipases destroy peripancreatic fat as well as abdomen and subcutaneous tissue – discolouration of the skin
what are the consequences of pancreatic tissue destruction in acute pancreatitis?
Hypocalcaemia • Liquefactive haemorrhagic necrosis • Pancreatic pseudocyst • Destruction of islets cells = hyperglycaemia = type II diabetes • Pulmonary failure
how does pancreatitis lead to pulmonary failure?
circulating activated digestive enzyme leads to loss of surfacrnt, atelectasis and irritation leading to ARDS
what investigations should be done in acute pancreatitis?
Bloods CXR Contrast enhanced spiral CT ECG MRI/MRCP ERCP Operative biopsies or needle aspiration cytology
what will blood results show in acute pancreatitis?
- Raised amylase
- Raised lipase
- Raised blood glucose
- Moderate leucocytosis and anaemia in severe cases
- Serum bilirubin is often raised
- Hypoxia in extreme cases
- Low serum calcium
what scoring system is used in pancreatitis?
Glasgow Score – Acronym Pancreas
what are the criteria of the glasgow scoring system for pancreatitis?
o PO2 Oxygen < 60mmHg or 7.9kPa o Age > 55 o Neutrophilia White blood cells > 15 o Calcium < 2 mmol/L o Renal Urea > 16 mmol/L o Enzymes Lactate dehydrogenase (LDH) > 600iu/L Aspartate transaminase (AST) > 200iu/L o Albumin < 32g/L o Sugar Glucose > 10 mmol/L
what is the management of acute pancreatitis?
- Replace fluids
- Nasogastric suction
- Prophylactic antibiotics – broad spectrum – not given so routinely
- Analgesia
- Enteral nutrition
- With multiorgan failure – ventilation and renal support
what are th complications of acute pancreatitis?
- Hypovolemic Shock
- DIC
- ARDS
What are the causes of chronic pancreatitis?
- Alcohol
- Genetic - associated with aminoaciduria or hyperparathyroidism or cystic fibrosis
- Obstruction – benign or malignant
- Congenital abnormalities – pancreas divisum
- Hypercalaemia
- Malnutrition
what is the pathophysiology of chronic pancreatitis?
Persistent inflammation leads to: - fibrosis of the ducts leading to narrowing
- calcification deposist on protein plugs
- pancreatic atrophy
what is the consequence of chronic pancreatitis of pancreas function?
Pancreatic insufficiency - fewer enzymes produced by acinar cells
damage to alpha and beta cells
what are the clinical consequences of chronic pancreatitis?
Problems absorbing fat (weight loss, fatty stools)
Diabetes
Pancreatic pseudocysts
pancreatic cancer
what are the clinical features of chronic pancreatitis?
- Pain in epigastric region – may radiate to back, linked to eating meals, lasts several houses
- Pancreatic Insufficiency – weight loss, deficient in vitamins, fatty stools
- Jaundice attributed to common duct blockage
what investigations can be done for chronic pancreatitis?
Bloods Xray, CT ERCP Faecal elastase levels PABA and pancteolauryl tests
what will blood results in chronic pancreatitis show?
Lipase and Amylase may or may not be raised
what will ERCP in chronic pancreatitis show?
chain of lakes appearance – stenosis and dilatation
What is the management of chronic pancreatitis?
Pain relief – NSAIDs and opiates. Tricyclic antidepressants e.g. amitriptyline for chronic pain PPI Replace digestive enzymes Vitamins Diabetic management Manage risk factors
what are the modifiable risk factors associated with pancreatic carcinoma?
o Smoking
o Obesity
o Diet high in red meat
o Alcohol Abuse
what are the non-modifiable risk factors associated with pancreatic carcinoma?
o Male
o African American
o >65
what diseases are risk factors for pancreatic carcinoma?
o Diabetes o Pylori infection o Chronic pancreatitis o Partial Gastrectomy o Liver cirrhosis
what are the genes associated with pancreatic carcinoma?
o BRAC2
o PALB2
the pancreas is made up of which two cell types?
Endocrine
Exocrine
which cell type do pancreatic carcinomas commonly occur in?
exocrine
what are the different types of exocrine pancreatic carcinomas?
Adenocarcinoma (epithelial cells lining ducts)
Exocrine Tumours of Acinar Cells
Cystadenocarcinoma
Undifferentiated
where to pancreatic adenocarcinomas commonly occur?
60% occur in head, 25% in body, 15% in tail
where do pancreatic head adenocarcinomas arise from?
1/3 are periampullary, arising from the ampulla of Vater, the duodenal mucosa or the lower end of the common bile duct
what is the microscopic appearance of pancreatic adenocarcinomas?
tumours arising in the epithelial cells lining pancreatic ducts
what is the macroscopic appearance of pancreatic adenocarcinomas?
infiltrating, hard, irregular
where to pancreatic adenocarcinomas commonly invade into?
CBD Duodenum Portal Vein Superior Mesenteric Artery Inferior Vena Cava
what lymph nodes do pancreatic adenocarcinomas spread to?
To adjacent lymph nodes and nodes in the porta hepatis
what is pancreatic adenocarcinoma trans coelomic spread?
With peritoneal seeding and ascites
what are the clinical features of pancreatic adenocarcinoma?
Nausea, vomiting, fatigue, Weight loss
Mid-epigastric pain
o Radiates to mid/lower back
o Worse when lying flat
what are the symptoms of advanced pancreatic carcinomas?
o Trousseau = Blood clots felt as small lumps under skin
o Courvoisier
Gallbladder enlarged and palpable, non tender
o Pulmonary Emboli – SOB, chest pain
o Diabetes – polyuria, polydipsia
o Ascites
what are the tumour location affects of pancreatic carcinomas?
o Head – obstruction of common bile duct = obstructive jaundice
Loss of appetite, darker urine, lighter stools, pruritis, yellowing
o Endocrine = New onset diabetes
what will blood tests in pancreatic carcinoma show?
o Nonspecific - Serum amylase and lipase elevated, Ca 19-9 antigen increased, CEA increased
o Obstructive jaundice - Raised alkaline phosphate, transaminase
o Anaemia
o Hyperglycaemia
o Hypokalaemia
o Hypercalcaemia
what imaging can be used for pancreatic adenocarcinoma?
o US
o CXR
o Endoscopic US or biopsy – endoscopy can help diagnosis, histology not required for formal diagnosis
o CT/PET
what are the stages of pancreatic carcinoma?
- Less than 2cm
- Greater than 2cm
- Growing into neighbouring tissue 4. Metastatic
what are the management options for pancreatic carcinoma?
- Chemotherapy = Neoadjuvant, adjuvant or in non-surgical treatment
- Radiotherapy – reserved for adjuvant usage in potentially curable
- Whipple Procedure
what is a whipple procedure?
Due to shared blood supply – removal of gall bladder, jejunum and stomach
What are the pancreatic islet cells?
Beta Alpha Delta Pancreatic Polypeptide cells Enterochromaffin cells D1 cells G cells
what do beta cells in the pancreas do?
Secrete insulin
what do alpha cells in the pancreas do?
Secrete glucagon
what do delta cells in the pancreas do?
secrete somatostatin
what do pancreatic polypeptide cells cells in the pancreas do?
secrete pancreatic polypeptide
what do enterochromaffin cells in the pancreas do?
secrete serotonin
what do D1 cells in the pancreas do?
secrete vasoactive intestinal peptide (VIPP)
what do G cells in the pancreas do?
secrete gastrin
how does insulin work?
Lowers blood glucose by transporting glucose into the cell and pushes potassium into the cell – decreases blood potassium
how does glucagon work?
- Raises blood glucose levels
* Gets liver to generate glucose from amino acids + lipids and break down glycogen into glucose
how does somatostatin work?
• Decreases release of insulin, glucagon and serotonin
how does pancreatic polypeptide work?
• Stimulates release of digestive enzymes from stomach + small intestines – slows down intestinal movement
what effect does serotonin have on the GI tract?
increases motility of GI tract
how does VIPP work?
Relaxes small intestine, stimulates digestive enzymes, inhibits hydrochloric acid
how does gastrin work?
stimulates parietal cells to produce hydrochloric acid
stimulates glands in the epithelium layer
what is the cause of pancreatic Pancreatic Neuroendocrine Tumours ?
• Mutation in the tumour suppressor Gene
o PTEN
o MEN1
MEN1 causes tumour formation in what organs?
parathyroid, pituitary, pancreas
what are the two kinds of pancreatic neuroendocrine tumours?
non functional and functional
what are the features of non functional pancreatic neuroendocrine tumour?
More common
Asymptomatic until they grow larger and metastases
Compress surrounding structures
what are the types of functional pancreatic neuroendocrine tumours?
Insulinoma Gastrinoma VIPoma Glucagonoma Somatostatinoma Pancreatic polypeptide cells and extrachromaffin cells rare
what is cell type forms an insulinoma?
beta cells
what is the pathophysiology of beta cells?
o Benign, solitary tumours
o High production of insulin
what are the clincial features of insulinoma?
Symptoms appear during hunger or exercise exercise and relieved by eating
CNS phenomena – weakness, sweating, trembling, epilepsy, confusion, hemiplegia and eventually coma
GI phenomena – hunger, abdo pain, diarrhoea
Excess appetite and weight gain
how are insulinomas diagnosed?
Whipple Triad
insulin levels
C-peptide levels
Imaging - CT, MR< EUS, selective angiography
what is whipples triad?
Attacks induced by startvation or exercise
During the attack hypoglycaemia is presrnt
Symptoms are relieved by sugar given orally or IV
what are the insulin levels in insulinoma?
raised in the presence of hypoglycaemia
what are the C-Peptide levels in insulinoma?
high with insulinoma, low the exogenous insulin administration
what is the management of insulinomas?
Tumour excision (+/- whipple)
what cell type makes up gastinoma?
G cells
what is the pathophysiology of gastrinomas?
o Secrete large amounts of gastrin = Excess hydrocholirc acid
what is the consequence of excess hyaluronic acid in gastrinomas?
Zollinger Ellison -Formation of peptic ulcers in stomach, dudoden, jejunum
Hydrocholirc acid also inactivates pancreatic digestive enzymes - Food passes through undigested = steatorrhea
how are gastrinomas diagnosed?
o Serum gastrin concentration x10 normal
o Basal acid output is high
o Localisation: as for insulinoma
what is the management of gastrinomas?
o Excision
o PPIs
o Symptoms relapse after cessation of treatment
what cell type form VIPomas?
D1 cells
what is the pathophysiology of VIPomas?
Excess vasoactive intestinal peptide
What are the clinical features of VIPomas?
WDHA syndrome
Watery diarrhoea – increased fluid secreted by small + large intestine
Hypokalaemia – low potassium in blood, due to losses in intestinal fluid
Achlorhydria – absence of hydrochloric acid
what cell type do glucagonomas arise from?
alpha cells
what are the clinical symptoms of glucagonoma?
Diabetes
necrolytic migratory ecthyma (rash affecting mouth and limbs)
what is the pathophysiology of glucagonoma?
Excess blood glucose – diabetes
Loss of lipids and proteins
what cell type do somatostatinomas form from?
delta cells
what is the pathophysiology of somatostatinomas?
o Excess somatostatin
Inhibits release of other pancreatic hormones (insulin, gastrin, VIP)
how can neuroendocrine pancreatic tumours be diagnosed?
Measure pancreatic hormone level
• CT/MRI
what are the clinical features of somatostatinoma?
steatorrhea, hypochlorhydria
how can neuroendocrine pancreatic tumours be treated?
Functional (except somatostatinomas)
o Somatostatin-like medications
o Gastrinomas – medications block gastric acid secretion
• Large tumours = surgery
