11.12 - Pancreatitis Flashcards
What are pancreatic acinar cells arranged around?
Intercellular canaliculus
What are the two components of pancreatic juice?
- exocrine component - low volume, viscous, enzyme-rich, from acinar cells
- high volume, watery, HCO3- rich, from duct and centroacinar cells
What are the acinar enzymes?
- lipases (fat)
- proteases (protein)
- amylase (carbohydrates)
- synthesised and stored in zymogen granules
What is the problem for an organ making a cocktail of digestive enzymes?
Autodigestion –> acute pancreatitis
What are the protective mechanisms for the enzymes?
- proteases are released as inactive pro-enzymes - protects acini and ducts from autodigestion
- pancreas contains a trypsin inhibitor to prevent trypsin activation
- enzymes are only activated in the duodenum
How are enzymes only activated in the duodenum?
- duodenal mucosa secretes enterokinase (enteropeptidase)
- converts trypsinogen into trypsin
- trypsin then converts all other proteolytic and some lipolytic pro-enzymes into enzymes
What is acute pancreatitis?
- rapid onset inflammation of the pancreas
- the pancreas is the grey mass in the middle - very oedematous = peripancreatic inflammation
What is the abbreviation for the aetiology (causes) for acute pancreatitis?
GETSMASHED
- Gallstones
- Ethanol (alcohol)
- Trauma
- Steroids
- Mumps and other viruses (EBV, CMV)
- Autoimmune (polyarteritis nodosa, SLE)
- Scorpion/snake bite
- Hypercalcaemia, hypertriglyceridaemia, hypothermia
- ERCP (endoscopic retrograde cholangiopancreatography) - cannulating common bile duct blindly, can accidentally enter main duct and trigger pancreatitis
- Drugs (SAND - steroids and sulphonamides, azothioprine, NSAIDs, diuretics [loop/thiazide])
What is the pathogenesis of acute pancreatitis?
- gall stones cause build up of pancreatic juice and therefore pressure in pancreatic duct
- gall stones block ampulla = bile juice from bile duct reflux into pancreatic duct
- weak ampulla = reflux of duodenal contents (activated enzymes) into pancreatic duct –> pancreas
- increased permeability of pancreatic duct epithelium by alcohol, acetylsalicyclic acid (aspirin), histamine = acinar cell enzymes diffuse into periductal interstitial tissue
- alcohol can precipitate proteins in ducts = plugs duct and increases upstream pressure
- pancreatic enzymes activated intracellularly - proenzymes and lyosomal proteases get incorporated into same vesicles by accident which activates trypsin
What can activation of trypsin intracellularly/extracellularly in pancreas activate?
- phospholipase A2
- elastase
- complement
- prothrombin
- kallikrein
What does phospholipase A2 do?
- causes fat necrosis which leads to Ca2+ sequestration –> saponification (soap formation) –> hypocalcaemia
- also causes hyperalbuminemia –> hypocalcaemia
What does elastase do?
- causes arrosion with bleeding - causes haemorrhagic pancreatitis
- causes islet necrosis which decreases insulin levels –> hyperglycaemia
What does complement do?
- leads to cell toxicity –> vessel arrosion –> bleeding –> pancreatic gangrene
- cell toxicity –> islet necrosis –> decreases insulin –> hyperglycaemia
What does prothrombin do?
Prothrombin –> thrombin –> thrombosis –> ischaemia –> pancreatic gangrene
What does kallikrein do?
Kallikrein –> bradykinin, kallidin –> vasodilation and plasma exudation –> pain and shock
What systemic damage can occur due to trypsin activation?
- phospholipase A2 and free fatty acids from fat necrosis can destroy the surfactants of the alveolar epithelium –> hypoxia
- kallikrein can lead to anuria
What are the three types of acute pancreatitis?
- oedematous pancreatitis - fluid build up
- haemorrhagic pancreatitis - bleeding pancreatitis
- necrotic pancreatitis - superseding infection, infected necrotic tissue
What are the symptoms of acute pancreatitis?
- epigastric pain radiating to back - often eased by sitting forward
- nausea and vomiting
- fevers - does not mean sepsis (infection) but because inflammatory reaction causes high temperatures
What are the signs of acute pancreatitis?
- haemodynamic instability (tachycardic, hypotensive) as you lose a lot of fluid
- peritonism in upper abdomen/generalised
- Grey-Turner’s sign - bruising in flanks (associated with haemorrhagic pancreatitis)
- Cullen’s sign - bruising around umbilicus (associated with haemorrhagic pancreatitis)
What are some of the differential diagnoses if not acute pancreatitis?
- gallstone disease and associated complications e.g. biliary colic and acute cholecystitis
- peptic ulcer disease/perforation
- leaking/ruptured AAA
What is a blood test for when investigating acute pancreatitis?
- elevated amylase/lipase
- other causes of elevated amylase include:
- parotitis
- renal failure
- macroamylasaemia
- bowel perforation
- lung/ovary/pancreas/colonic malignancies can produce ectopic amylase
What X-rays can be done when investigating acute pancreatitis?
- erect chest X-ray to exclude a perforated viscus
- abdominal X-ray (AXR) where you may see gallstones
What is an ultrasound for when investigating acute pancreatitis?
Look for gallstones as a cause for pancreatitis
When do we do a CT abdomen when investigating acute pancreatitis?
Patients not settling with conservative management & only 48-72 hours after symptom onset
When is MRCP done when investigating acute pancreatitis?
When gallstone pancreatitis is suspected with abnormal liver function tests (looking for common bile duct stone)
When is ERCP done when investigating acute pancreatitis?
- to remove common bile duct stones
- this is a therapy rather than an investigation
What are the criteria for assessing severity of acute pancreatitis?
Modified Glasgow criteria - PANCREAS
- P - PO2 < 8kPa
- A - age >55 years
- N - WCC > 15
- C - calcium <2mmol/L
- R - renal - urea >16mmol/L
- E - enzymes - AST >200 iu/L, LDH >600 iu/L
- A - albumin <32g/L
- S - sugar >10mmol/L
- score of 3+ within 48 hours of onset suggests severe pancreatitis
What is an independent predictor of severity of acute pancreatitis?
- CRP is an independent predictor of severity
- > 200 suggests severe pancreatitis
How is acute pancreatitis managed?
- ABC - airway, breathing, circulation
- 4 principles of management
- 95% settle with conservative treatment
- if severe pancreatitis on scoring - send to HDU (high dependency unit)
- antibiotics controversial - commence if necrotic pancreatitis/infected necrosis, but not routinely
- surgery only very rarely required
What are the four principles of management? (Acute pancreatitis)
- fluid resuscitation - IV fluids, urinary catheter to see if kidneys working properly, strict fluid balance monitoring
- analgesia
- pancreatic rest (+/- nutritional support if prolonged recovery - nasojejunal feeding or total parental nutrition)
- determining underlying cause
What are the systemic complications that can occur with acute pancreatitis?
- hypocalcaemia: lipase –> FFAs –> chelate Ca2+ salts –> less serum levels
- hyperglycaemia (diabetes if significant beta cell damage)
- SIRS (systemic inflammatory response syndrome)
- ARF (acute renal failure)
- ARDS (adult respiratory distress syndrome)
- DIC (disseminated intravascular coagulation)
- MOF (multi organ failure) + death
What are the local complications that can occur with acute pancreatitis?
- pancreatic necrosis +/- infection (infected necrosis)
- pancreatic abscess
- pancreatic pseudocyst
- haemorrhage - due to bleeding from eroded vessels - in small vessels we get haemorrhagic pancreatitis (Cullen’s/Grey Turner’s sign), in large vessels like splenic artery we can get life threatening bleed unless it forms a pseudoaneurysm (weakness in arterial wall secondary to arrosion)
- thrombosis of splenic vein, SMV, portal vein - interrupted flow back to liver can cause ascites (fluid in abdomen) + small bowel venous congestion/ischaemia
- chronic pancreatitis/pancreatic insufficiency (if recurrent attacks)
What is pancreatic pseudocyst?
- peripancreatic fluid collection (with pancreatic enzymes) within a fibrous capsule
- presents >6 weeks after pancreatitis
- 95% spontaneously resolve over 6 months
A pancreatic pseudocyst normally requires no intervention unless what?
- pseudocyst symptomatic (pain)
- pseudocyst causing compression of surrounding structures e.g. CBD (obstructive jaundice), duodenum (high SBO)
- pseudocyst infected (abscess)
- requires drainage of pseudocyst
How does pseudocyst drainage work?
- percutaneously under radiological guidance (CT)
- endoscopically - EUS puncturing posterior wall of stomach and inserting stent so the fluid drains from pancreas into stomach
- surgically via laparoscopic/open-pseudocystgastrostomy (cyst opened into stomach), pseudocystjejunostomy
What is the management for infected necrosis acute pancreatitis?
- antibiotics and percutaneous drainage
- infected pancreatic necrosis is only an indication for surgery in context of acute pancreatitis - high mortality if dead infected tissue is not debrided
- surgery involves necrosectomy (excision of necrotic tissue)
What is chronic pancreatitis?
- long-standing inflammation of the pancreas
- commonly pancreatic stones of calcium (white circles just above middle of image) that occur in main ducts but also within pancreas called intraparenchymal stones
What does chronic pancreatitis lead to?
- destroys endocrine and exocrine tissue and leads to fibrosis of pancreas
- insulin-dependent diabetes mellitus and steatorrhea
How is chronic pancreatitis caused?
- alcohol abuse –> decreased secretion of HCO3- and fluid in pancreatic juice which increases proenzyme concentration
- leads to protein plug and calcium deposition –> epithelial lesions and enzyme activation
- alcohol abuse also decreases citrate and lithostatin concentrations which promotes Ca2+ salt precipitation –> calcium deposition
What does an increase in pressure from calcium stones lead to?
- pain
- malabsorption - weight loss
- tissue atrophy
- ductal stenosis
- periductal fibrosis
- diabetes mellitus
- pancreatic ascites - pancreatic fluid leaking into abdomen
- thrombosis of portal and splenic veins
- obstructive jaundice
- diarrhoea
- pseudocysts
How is chronic pancreatitis managed?
- only intervene if there is pain
- can see big white stone in scan
- endoscopic with ERCP can pull stone out, or lithotripsy if not
- can put stent in so pancreatic juice can get to where it needs to go
- can do surgery by opening pancreas and removing stones - can also join part of small bowel onto pancreas = pancreatic juice not obstructed
- can take away parts of pancreas - total/distal/proximal pancreatectomy
