1. Pancreas
Tavassoli,Alireza

2. نام درس :بيمار يهاي پانكراس اهداف
نام درس :بيمار يهاي پانكراس اهداف
1-بيماري هاي پانكراس رابشناسد
2-عوامل سبب زاي بيماري هاي پانكراس را بشناسد
3- راه هاي پيشگيري بيماري هاي پانكراس را بداند.
4- نحوه مراقبت بيماري هاي پانكراس را فراگيرد. (Surveillance)
5-عوامل خطرزاي بيماري هاي پانكراس را بداند
6- ويژگي هاي اپيدميولوژيك بيماري هاي پانكراس را بشناسد .
7-روش هاي تشخیصی بيماري هاي پانكراس رابشناسد.
8- روش هاي درمان را بداند.

3. Normal Anatomy & Physiology
neutralize chyme
digestive enzymes
hormones
The pancreas lies in the retroperitoneum nestled in the C-loop of the duodenum and posterior to the stomach.
Physiologic function of the pancreas. The
human pancreas has three general functions:
(1) neutralizing the acid chyme entering the duodenum from the stomach;
(2) synthesis and secretion of digestive enzymes after a meal; and
(3) systemic release of hormones that modulate metabolism of carbohydrates, proteins, and lipids.

4. Exocrine Function pancreatic enzymes common bile duct pancreatic duct
BODY
common bile
duct
TAIL
HEAD
ampulla
pancreatic duct
To understand pancreatitis, you need a basic understanding of pancreatic exocrine function
UNCINATE
pancreatic enzymes

5. Enzyme Secretion acinus pancreatic duct microscopic view
The pancreatic acinar cells are specialized cells which synthesize, store, and secrete digestive enzymes
These digestive enzymes are stored in zymogen granules (shown in blue) which serve as a compartment for inactive pro-enzymes thus preventing auto-activation.
pancreatic duct
microscopic view
of pancreatic acini
duodenum

6. Enzyme Secretion Neural Hormonal Secretin (hormonal) acetylcholine VIP
GRP
Hormonal
CCK
gastrin
Enzyme secretion is stimulated by neural pathways or by hormones with 2 most potent stimulators being CCK and secretin.
The pancreatic fluid is rich in bicarbonate which makes it alkaline and the total daily volume is approx. 2.5 L.
Secretin (hormonal)
H2O
bicarbonate

7. Digestive Enzymes in the Pancreatic Acinar Cell
PROTEOLYTIC LIPOLYTIC ENZYMES
ENZYMES Lipase
Trypsinogen Prophospholipase A2
Chymotrypsinogen Carboxylesterase lipase
Proelastase
Procarboxypeptidase A NUCLEASES
Procarboxypeptidase B Deoxyribonuclease (DNAse)
Ribonuclease (RNAse)
AMYOLYTIC ENZYMES
Amylase OTHERS
Procolipase
Trypsin inhibitor
There are several different classes of digestive enzymes secreted by the pancreatic acinar cells. Most of these enzymes are proenzymes which are inactive with the exceptions of amylase and lipase.
Protein
Starch and glycogen
Fat
Amino acids
Other

8. Exocrine Stimulation
The more proximal the nutrient infusion…the greater the pancreatic stimulation (dog studies)
stomach – maximal stimulation
duodenum – intermediate stimulation
jejunum – minimal / negligible stimulation
Elemental formulas tend to cause less stimulation than standard intact formulas
intact protein > oligopeptides > free amino acids
Intravenous nutrients (even lipids) do not appear to stimulate the pancreas

10. Acute Pancreatitis

11. Clinical Case A man with acute onset abdominal pain h/o alcohol intake
Or Gall stone
A 32-year-old man is admitted to the hospital with acute onset abdominal pain of presumed pancreatic origin.

12. Acute Pancreatitis Definition
Acute inflammatory process involving the pancreas
Usually painful and self-limited
Isolated event or a recurring illness
Pancreatic function and morphology return to normal after (or between) attacks
Here are the details…

13. Acute Pancreatitis Etiology

14. Acute Pancreatitis Associated Conditions
Cholelithiasis
Ethanol abuse
Idiopathic
Medications
Hyperlipidemia
ERCP
Trauma
Pancreas divisum
Hereditary
Hypercalcemia
Viral infections
Mumps
Coxsackie virus
End-stage renal failure
Penetrating peptic ulcer

15. Acute Pancreatitis Causative Drugs
AIDS therapy: pentamidine ,didanosine
Anti-inflammatory: sulindac, salicylates
Antimicrobials: metronidazole, sulfonamides, tetracycline, nitrofurantoin
Diuretics: furosemide, thiazides
IBD: sulfasalazine, mesalamine
Immunosuppressives: azathioprine, 6-mercaptopurine
Neuropsychiatric: valproic acid
Other: calcium, estrogen, tamoxifen,

16. Pancreas divisum

17. Hereditary Pancreatitis
Autosomal dominant with 80% phenotypic penetrance
Recurrent acute pancreatitis, chronic pancreatitis, and 50-fold increased risk of pancreatic cancer

18. Pancreatitis Background
Potentially fatal
Mortality – 10-15%
Necrosis determines the prognosis
Acute pancreatitis is a potentially fatal disease, with reported mortality rates ranging from zero to almost 25%, depending on severity. Severity itself depends greatly on whether or not pancreatic necrosis is present. Since majority of the patients with mild acute pancreatitis recover without any short term complications or long term sequelae. So majority of the studies have focussed on management of acute necrotizing pancreatitis. I would also

19. Background Mild AP (no necrosis) – 0% Sterile necrosis – 10%
Infected necrosis – 25%
Overall mortality: %
Since majority of the patients with mild acute pancreatitis recover without any short term complications or long term sequelae. So majority of the studies have focussed on management of acute necrotizing pancreatitis. I would also

20. What do you think? Amylase or lipase Ultrasound or CT scan
If yes, When?
ICU or medical ward
Enteral nutrition or TPN
Antibiotics
ERCP
Surgery

21. Epidemiology of acute pancreatitis
There appears to be an increase in the incidence of acute pancreatitis.
This rise attributed to increased alcohol consumption
No seasonal or weekly
Men are affected much more than women
Main age group affected is 40–60 year olds.

22. Acute Pancreatitis Pathogenesis
acinar cell
injury
failed protective mechanisms
premature enzyme activation
talk about failure of compartmentalization, premature activation, and overwhelming or absence of inhibitors

24. Acute Pancreatitis Pathogenesis
premature enzyme activation
autodigestion of pancreatic tissue
local
vascular
insufficiency
activation
of white
blood cells
release of enzymes into
the circulation
local complications
distant organ failure

25. Acute Pancreatitis Pathogenesis
SEVERITY
Mild
Severe
STAGE 1: Pancreatic Injury
Edema
Inflammation
STAGE 2: Local Effects
Retroperitoneal edema
Ileus
STAGE 3: Systemic Complications
Hypotension/shock
Metabolic disturbances
Sepsis/organ failure
Three stages of pathophysiology of acute pancreatitis
The pathophysiology of
acute pancreatitis can be considered as involving three stages. The first stage
is pancreatic injury with edema, inflammation, necrosis of pancreatic fat, and
variable degrees of necrosis of pancreatic secretory cells. The second stage is
spread of the inflammatory process to surrounding tissues, with development of
retroperitoneal edema, peripancreatic fat necrosis, and an ileus, with ;third
spacing; of fluid and electrolytes in the gastrointestinal tract resulting in
hemoconcentration (increased hematocrit). The third stage involves systemic
complications, such as hypotension/shock, multiorgan system failure (eg,
respiratory, renal), metabolic disturbances, such as hypoalbuminemia and
hypocalcemia, and sepsis.

26. Pathophysiology of necrosis infection

27. Pancreatitis Clinical Presentation
Pain: Steady & severe in nature; located in the epigastric or umbilical region; may radiate to the back. Worsened by lying supine; may be lessened by flexed knee, curved-back position.
Vomiting: Varies in severity, but is usually protracted, worsened by ingestion of food or fluid. Does not relieve the pain. Usually accompanied by nausea.

28. Pancreatitis con’t…… Fever: Rarely exceeds 39 C.
Abdominal Finding: Rigidity, tenderness, guarding, distended Abd, decreased or absent peristalsis and paralytic ileus.Fatty stools-(steatorrhea)
Laboratory Finding: Elevation of WBC count ,000. lipase and amylase(5 to 40 times); elevated(glucose, bilirubin, alkaline phosphatase.,Urine amylase).Abnormal low serum CA, Na & Mg.-due to dehydration. Binding of Ca in areas of fat necrosis.

29. Acute
Pancreatitis

30. Acute
Pancreatitis

31. Acute
Pancreatitis

32. Acute
Pancreatitis

38. Acute Pancreatitis Differential Diagnosis
Choledocholithiasis
Perforated ulcer
Mesenteric ischemia
Intestinal obstruction
Ectopic pregnancy

39. Acute Pancreatitis Diagnosis
Symptoms & Signs
Abdominal pain
Laboratory
Elevated amylase or lipase
> 3x upper limits of normal
Imaging
Abnormal sonogram or CT

40. Acute Pancreatitis Diagnosis
EtOH: history
Gallstones: abnormal LFTs & sonographY
Hyperlipidemia: lipemic serum, Tri>1,000
Hypercalcemia: elevated Ca
Trauma: history
Medications: history

41. Abdominal Exam Skin Exam Abdominal tenderness and rigidity
Bowel sounds decreased
Palpable upper abdominal mass Acute fluid collections and pseudocysts
Skin Exam
Erythematous skin Nodule (Subcutaneous Fat Necrosis)
Cullen's Sign (periumbilical discoloration)
Turner's Sign (flank discoloration) * due to exudation of blood-stained fluid into the subcutaneous tissue, usually 72 h into the illness.

43. Acute Pancreatitis Clinical Manifestations
PANCREATIC
PERIPANCREATIC
Adjacent viscera:
SYSTEMIC
Mild: edema, inflammation, fat necrosis
Severe: phlegmon, necrosis, hemorrhage, infection, abscess, fluid collections
Retroperitoneum, perirenal spaces, mesocolon, omentum, and mediastinum
ileus, obstruction, perforation
Cardiovascular: hypotension
Pulmonary: pleural effusions, ARDS
Renal: acute tubular necrosis
Hematologic: disseminated intravascular coag.
Metabolic: hypocalcemia, hyperglycemia

44. Diagnosis: Biochemical
Serum Amylase elevated
Nonspecific
Returns to normal in hours
Normal amylase does not exclude pancreatitis
Level of elevation does not predict disease severity
Serum Lipase elevated
Specific for pancreatic disease
Returns to normal in 7-14 days

45. Diagnosis: Biochemical
White Blood Cells
increased to 15k-20k
Hypertriglyceridemia (15%)
liver Function Tests
(ALP) (AST) ,elevated
(LDH) elevated (Poor prognosis)
Hyperglycemia
Albumine
(Poor prognosis)
Serum Electrolytes
Hypocalcemia (25%)

46. Acute Physiology And Chronic Health Evaluation
Another criteria often used to assess the severity of pancreatitis is the (APACHE-II) .
Acute Physiology And Chronic Health Evaluation
age and vital signs
Specific laboratory parameters,
Chronic health status
The main advantage is the immediate assessment of the severity of pancreatitis.
A score of eight or more at admission is usually considered indicative of severe disease

48. Predictors of Severity
Why are they needed?
Appropriate triage & therapy
compare results of studies of the impact of therapy
When are they needed?
optimally, within the first 24 hours
Which is the best?

49. Ranson Criteria Alcoholic Pancreatitis
AT ADMISSION
Age > 55 years
WBC > 16,000
Glucose > 200
AST > 250 IU/L
LDH > 350 IU/L
WITHIN 48 HOURS
HCT drop > 10%
BUN > 5
Arterial PO2 < 60 mm Hg
Base deficit > 4 mEq/L
Serum Ca < 8
Fluid sequestration > 6L
Number
<2 1%
3-4
16%
5-6
40%
7-8
100%
Mortality

50. Glasgow Criteria Non-alcoholic Pancreatitis
WBC > 15,000
Glucose > 180
BUN > 16
Arterial PO2 < 60 mm Hg
Ca < 8
Albumin < 3.2
LDH > 600 U/L
AST or ALT > 200 U/L

51. Balthazar et al. Radiology 1990.
CT Severity Index
appearance
normal
enlarged
inflamed
1 fluid collection
2 or more collections
grade A B C D E
score 1 2 3 4
necrosis
none
< 33%
33-50%
> 50%
score 2 4 6
So, even if we can’t identify severe cases sooner, the CT index appears to be the best way to judge severity.
score
morbidity
mortality
1-2 4% 0%
7-10
92%
17%
Balthazar et al. Radiology 1990.

52. Useful markers of severe disease.
Pleural effusion
BMI (High body mass index)
Necrosis on contrast-enhanced CT-SCAN
CRP level greater than 150 mg/L at 48 h
Infection of the necrotic tissue after the first week of illness is the major determinant of later outcome.

53. Pancreatic necrosis

54. CT-guided percutaneous fine-needle aspiration of the pancreatic tail

55. Immediate assessment Clinical assessment including great care to assess respiratory, cardiovascular and renal compromise.
Organ failure ?
BMI?. There is considerable risk (> 30 kg/m2) or much greater risk > 40 kg/m2
Chest X-ray. Is there a pleural effusion present?
CT.Scan Is there more than 30% of the volume of the pancreas malperfused?
Scoring. Is it high score or low?

57. Resuscitation
Transudation of fluid from the intravascular space to the peritoneum is the principle cause of hypovolemia in AP.
Assessment of the patient’s volume status determined by heart rate, blood pressure, urine output and CVP line.

58. Treatment of Mild Pancreatitis
Pancreatic rest
Supportive care
fluid resuscitation – watch BP and urine output
pain control
NG tubes ,H2 blockers ,PPIs helpful??
Refeeding (usually 3 to 7 days)
bowel sounds present
patient is hungry
nearly pain-free (off IV narcotics)
amylase & lipase not very useful here
mild panc – support is all that’s needed
hypotension probably predisposes to necrosis (poor microcirculation)

59. Treatment of Severe Pancreatitis
Pancreatic rest & supportive care
fluid resuscitation* – may require 5-10 liters/day
careful pulmonary & renal monitoring – ICU
maintain hematocrit of 26-30%
pain control – PCA pump
correct electrolyte derangements (K+, Ca++, Mg++)
Rule-out necrosis
contrasted CT scan at hours
prophylactic antibiotics if present
surgical debridement if infected
Nutritional support
may be NPO for weeks, TPN
*common serious error to underestimate volume needs
may need SG catheter – lookout for ARF or ARDS
we have impacted the early mortality by better support…late mortality still problem

60. Analgesia
Severe pain should be treated with meperidine 50 to 100 mg IM q 3 to 4 h prn in patients with normal renal function (morphine causes the sphincter of Oddi to contract and should be avoided).

61. Antibiotic prophylaxis
Infectious complications are still regarded as the primary cause of mortality in severe pancreatitis.Thus, it is essential to identify the presence of pancreatic necrosis and take measures to prevent infection.
The current recommendation is the use of a systemic antibiotic such as imipenem-cilastatin 500 mg three times a day for 2 weeks in patients with documented pancreatic necrosis.

62. Role of ERCP in pancreatitis
1-Gallstone pancreatitis
Cholangitis
Obstructive jaundice
2-Recurrent acute pancreatitis
Structural abnormalities
Neoplasm
Bile sampling for microlithiasis
3-Sphincterotomy in patients not suitable for cholecystectomy

63. Reduced Oral Intake in Acute Pancreatitis
Abdominal pain with food
Nausea and vomiting
Gastric atony
Ileus
Partial duodenal obstruction

64. Summary
1-The overall mortality ranges from 2 to 10%. The incidence in males is usually 10–30% higher than in females.
2-The commonest cause is gallstones with alcohol being the next most common cause.
3-Patients with acute pancreatitis present with upper abdominal pain and/or different degrees of organ failure.
4-The diagnosis is suspected by a typical clinical presentation and supported by raised serum amylase. Atypical presentations may require confirmation by CT imaging.
5-Immediate management comprises analgesics, intravenous fluids and monitoring.

65. 6-Acute pancreatitis, severity best defined by failure of one or more organ systems and/or the Acute Physiology and Chronic Health Evaluation, (APACHE II) score of 8 or more.
7-Gallstone etiology is usually identified by early routine abdominal ultrasonography.
8-The majority of patients have mild pancreatitis and recover without additional treatment.
9-In 20%, the disease is severe and is associated with a mortality of about 20%.
10-Patients with severe pancreatitis require management in a high dependency or intensive care setting; this may require transfer to a specialized unit.
11-Clinical severity is paralleled by the degree of pancreatic and peripancreatic tissue necrosis as defined by dynamic CT.
12-Antibiotic prophylaxis is advised in patients with greater than 30% necrosis and imipenem is recommended currently.

66. 12- Enteral nutrition probably retains the integrity of the intestinal mucosal barrier and hence early mesenteric feeding is recommended. Parenteral nutrition is rarely indicated.
13- In patients with severe gallstone pancreatitis, early endoscopic retrograde cholangiography is indicated and, where appropriate, a sphincterotomy and clearance of the bile duct.
14--Where infection of pancreatic necrosis is proved by the presence of positive FNA or free gas in the area of necrosis, surgical intervention is indicated.
15--In sterile necrosis, continued conservative management is justified.
16--Patients with gallstone pancreatitis should either undergo cholecystectomy or endoscopic sphincterotomy and bile duct clearance prior to discharge.
17--Acute fluid collections are a feature of severe acute pancreatitis and often resolve spontaneously.
18--Pancreatic and peripancreatic abscesses, symptomatic pseudocysts and other ductal disruptions require interventional treatment.

67. Factors Differentiating Mild from Severe Pancreatitis
Parameter
Mild
Pancreatitis
Severe
Admissions
80%
20%
Pancreatic necrosis No
Yes
Oral diet within 5 days 0%
Morbidity 8%
38%
Mortality 3%
27%

68. Total Enteral Nutrition in Severe Pancreatitis
may start as early as possible
when emesis has resolved
ileus is not present
nasojejunal route preferred over nasoduodenal
likely decreases risk of infectious complications by reducing transmigration of colonic bacteria

69. Conclusions ( MOUSE CLICK)
Acute pancreatitis is a self-limited disease
Most cases are mild.
Gallstones and alcohol are the leading causes of acute pancreatitis.
In mild pancreatitis, nutritional support is usually not required
In severe pancreatitis, nutritional support will likely be required with the enteral route preferred over TPN because of both safety and cost.

70. Evidence A. Proven B. Possible/ Probable C. Consensus
> 2 well designed trials, randomized
B. Possible/ Probable
1 well designed study, randomized
C. Consensus
agreed opinion with no supportive evidence