Pancreatitis 2
Terms
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- Ampullary Anatomy:
-
- Common bile duct and pancreatic duct join near the ampulla
-Sphinct er of Oddi (SO) lies within the Papilla of Vater and relaxes to release duct contents into duodenum -
Major functional units and their secretory products:
Acinus - proenzymes -
proenzymes
- chymotrypsinogen
- kallikreinogen
- procarboxypeptidase A & B
- phospholipase (I, II)
- proelastase
- mesotrypsin
- trypsinogen (1, 2, 3) -
Major functional units and their secretory products:
Acinus - enzymes -
enzymes
- α-amylase
- sterol esterase
- lipase
- DNase
- RNase
- lysosomal enzymes - Classes of enzymes in pancreatic juice:
-
- proteases – 90%
- amylase – 7%
- lipases – 2%
- nucleases -- <1% - Acinus - Protective mechanisms:
-
- enzymes synth as inactive zymogens
- trypsin inhibitor packaged in zymogen granule
- segregation of enzymes in mbrn-bound compartments
- enterokinase is restricted to small intestine -
Major functional units and their secretory products:
Duct -
o water
o electrolytes - Zymogen Activation - general
-
- zymogens and trypsinogen exit into duodenum
- enterokinase in the small intestine (from enterocytes) activates trypsinogen to trypsin
- trypsin activates the zymogens to active enzymes - Zymogen Activation - specific examples
-
chymotrypsinogen to chymotrypsin
kallikreinogen to kallikrein
procarboxypeptidases to carboxypeptidases
procolipases to colipases
prophospholipases to phospholipases
proelastase to elastase
proprotease E to protease E
trypsinogen to trypsin -
Acute Pancreatitis
Characteristics -
- acute inflamm process of the pancreas that may involve peripancreatic tissues and remote organ systems
- characterized by inappropriate activation of pancreatic enzymes causing an “autodigestive†process that can result in signif morbidity and mortality
- most recover w/ return to normal pancreatic fxn -
Acute Pancreatitis
Etiology -
1. Alcoholic
2. Biliary
-- common channel theory:
stone migrates from gallbladder and sticks in ampulla; bile refluxes into pancreas
-- obstructed pancreatic duct theory:
back pressure on pancreatic duct so enzymes are activated w/in duct; seen in Pancreas Divisum in which panc duct sphincter is too small causing partial pancreatic obstruction (does not always cause pancreatitis)
2. Idiopathic
3. Other
-- autoimmune, drug-induced, iatrogenic, IBD-related, infectious, inherited, metabolic, neoplastic, structural, toxic, traumatic, vascular
-- most common drug induced are from asparaginase, azathiprine, 6-MP, DDI, pentamidine, valproate
-- environmental toxic causes: (MESO) methanol, ethylene, scorpion toxins, organophosphate insecticides
-- traumatic pancreatitis – usually blunt force trauma (car accident, stomach punch) -
Acute Pancreatitis
Pathophysiology -
No matter the inciting event:
1. intra-acinar activation of pancreatic zymogens causing autodigestion of the organ and surrounding tissues
2. causes inflamm rxn w/ release of inflamm mediators that can move through circ & lymph system to affect remote organs – lungs, kidney, heart
3. can cause circulatory collapse (shock) -
Acute Pancreatitis
Natural History -
80-90% have mild pancreatitis
~10% are severe cases, some of which will result in death
Early death (<1wk)
Multiorgan failure due to systemic inflamm response syndrome (SIRS) – ARDS, heart/kidney failure, CNS signs
Late death (>1wk)
Multiorgan failure due to pancreatic infection/sepsis -
Acute Pancreatitis
Presenting Signs -
abdominal pain
n/v
tachycardia
low grade fever
abdominal guarding
loss of bowel sounds
occasional jaundice
Gray Turner sign – sign of retroperitoneal bleed -
Acute Pancreatitis
Major Complications -
Local
- fluid collections
- necrosis
- infection
- ascites (↑amylase in fluid) - multiorgan failure
- erosion into adjacent
structures
- GI obstruction
- Hemorrhage
Systemic
- pulmonary
- renal
- CNS
- multiorgan failure
Metabolic -hypocalcemia -hyperglycemia -
Acute Pancreatitis
Diagnostic Lab Tests -
Serum enzymes -- >3x normal increases specificity (amylase and lipase)
Conditions assoc w/ hyperamylasemia AND hyperlipasemia:
intestinal obstruction, ulceration, ischemia, AND perforated viscus (so make sure to r/o these causes) -
Acute Pancreatitis
Imaging Tests -
US – best for gallbladder stones
CT – detects edema, calcifications, fluid collections
CT w/ contrast – detects necrosis -
Acute Pancreatitis
Ranson’s criteria of severity (3+ is severe) -
Admission:
Age >45 yrs,
WBC > 16k,
Glucose > 200,
LDH > 350,
AST > 120
After 48 hours:
-HCT decrease >10%
-BUN increase >5mg/dl
-Ca < 8mg/dl
-PaO2 < 60mmHg
-Base deficit > 4mEq/L
-Negative fluid balance >6L
Mortality increases with each criterion added -
Acute Pancreatitis
Treatment -
Supportive Care:
- aggressive fluid and electrolyte replacement
- monitor: vitals, urine output, O2 Sat, pain
- analgesia, anti-emetics
Other treatments:
- acid suppression
- antibiotics
- NG tube
- nutritional support
- urgent ERCP -
Chronic Pancreatitis
Characteristics -
- inflamm disease of pancreas that results in permanent damage to the structure and fxn of the organ
- characterized by: pain, malabsorption, diabetes -
Chronic Pancreatitis
Etiology -
1. Alcoholic
-- abnormal secretion of protein, electrolytes, bicarb
-- necrosis-fibrosis
-- calcification, fibrosis, decreased blood flow, and altered protein synth are chronic effects of EtOH
2. Idiopathic
3. Inherited causes -- proposed mech that trypsin not degraded and thus activates zymogen cascade
-- cystic fibrosis – gene mutation of CFTR
-- hereditary pancreatitis – trypsinogen gene mutation
-- familial hypertriglyceridemia – metabolic
- free f.a. have direct toxic effect on acinar cells
- rare cause acute pancreatitis
- serum TGs usually >1000
- can also be drug-induced hypertriglyceridemia
4. Other
-- autoimmune
-- fibrocalcific – seen in India/Africa; usually due to malnutrition -
Chronic Pancreatitis
Pathophysiology -
Necrosis- Fibrosis
-- repeated episodes of acute inflamm secondary to direct cytotoxic effects of EtOH on acinar cells
-- acute attacks lead to necrosis and duct disruption
-- healing leads to progressive fibrosis of ducts and obstruction
Abnormal secretion theory
-- hypersecretion of protein from acinar cell
-- increased secretion of ionized Ca
-- defects in HCO3 secretion decreased solubility of secreted proteins
-- decreased secretion of lithostatine
Secretory defects lead to:
-- Ca-protein precipitates in ducts
-- progressive blockage of ductules and main duct
-- structural deterioration of ducts, acinar cells, and islets of Langerhans
-- pancreatic insufficiency -
Chronic Pancreatitis
Natural History -
Increased pancreatic cancer risk in hereditary pancreas
Causes pain, calcifications, and pancreatic insufficiency leading to diabetes -
Chronic Pancreatitis
Presenting Signs -
Pain
-- intermittent or constant
-- moderate to severe
-- epigastric w/ radiation to back
Steatorrhea (once 90% pancreatic fxn gone)
-- visible oil droplets or grease in stool
-- increase volume, light color, foul odor -
Chronic Pancreatitis
Major Complications -
1. Pseudocyst – collection of fluid w/ no real capsule; “capsule†is fibrous tissue of adjacent organs; can be extra or intrapancreatic
2. Gastric or duodenal obstruction
3. Biliary obstruction
4. Pancreatic ascites; pleural effusion
5. Splenic vein thrombosis - gastric varices
6. Pseudoaneurysm – eruption of blood vessel due to pseudocyst -
Chronic Pancreatitis
Diagnostic Lab Tests -
Stool fat assay – measures fat digestion and absorption
Duodenal tube/secretin-CCK stim – assay of volume, enzymes, HCO3 to measure protease and electrolyte secretion
**most sensitive test for chronic pancreatitis
LESS OFTEN:
Stool – assay of stool elastase-1 and chymotrypsinogen to measure protease secretion
Urine – pancreatolauryl test to measure protease secretion -
Chronic Pancreatitis
Imaging Tests -
-- Abdominal X-ray – calcifications
-- Ultrasound – good for biliary tree
-- CT – best choice
-- EUS – endo US; can biopsy during procedure; very sensitive
-- MRCP – very sensitive, but can’t do therapeutics
-- ERCP
-- PET
** calcifications of pancreas are pathognomonic of chronic pancreatitis! -
Chronic Pancreatitis
Treatment -
Nutritional management:
-- Modify fat intake (decrease)
-- Medium chain triglycerides
-- Enzyme replacement
(coated vx. uncoated)
(acid suppression)
--Vitamins (supplements
fat soluble, calcium
cyanocobalamin (B12))
Pain Management -Effectiveness
No alcohol (low to moderate)
Analgesia (moderate)
Enzyme replacement(low)
Neurolytic Tx (moderate -short-term)
Pseudocyst drainage (high)
Duct decompression (moderate)
Stone removal- controversial -
General comparison of
acute vs. chronic -
ACUTE
-- acute inflamm
-- acute abdom pain
-- elevated pancreatic
enzymes in serum
-- self-limiting
CHRONIC
-- chronic inflamm
-- chronic abdominal pain
-- progressive loss of
pancreatic endocrine and exocrine fxn