LABORATORY MARKERS OF PANCREAS DISEASES

Rina Sidharta, dr., Sp.PK

FK UNS - 2013

The Pancreas

Anatomy of Pancreas
Retroperitoneal organ
Obliquely from the duodenal Cloop to the hillum of the spleen.

Anatomy of Pancreas
Pancreas is divided into 4 portions: head, neck, body, tail. The head is intimately associated with the second portion of duodenum.
Function: a. Endocrine b. Exocrine

Pancreas Endocrine
1. Insulin Insulin is released into the portal blood. Controlled by: a. concentration of blood glucose. b. vagal interaction c. local concentrations of somatostatin.

Pancreas Endocrine
2. Pancreatic polypeptide Function: a. regulation of pancreatic exocrine secretion. b. biliary tract motility. 3. Somatostatin Has abroad inhibitory spectrum of gastrointestinal activity.

Pancreas Exocrine
The final product of the exocrine pancreas:
- clear isotonic solution
pH: range of 8. - pancreatic fluid: Enzymes secretion Water and electrolytes secretion

Pancreatic Enzymes
a. Protease: - proenzyme tripsinogen, chymotripsinogen. Protein metabolism. b. Pancreatic lipase Lipid metabolism. c. Pancreatic Amylase Carbohydrate metabolism. d. Others: Ribonuclease, deoxyribonuclease, gelatine, elastase.

Pancreatic Enzymes
Stimulation by: a. Cholesystokinin: the most potent endogenous hormone to stimulate enzyme secretion. b. Secretin: The most potent endogenous stimulant of pancreatic electrolyte secretion.

The Pancreatic Diseases

1. Infection
Incidence: 1990 2000 increase 10 times. Mortality: 2 -9 percent. a. Acute pancreatitis n its complications b. Chronic pancreatitis n its complications

2. Carcinoma

Acute Pancreatitis
acute inflamatory process of the pancreas can involve per pancreatic tissues or remote organs system, or both mortality: - 5 10% - SIRS (System Inflammatory Response Syndrome). - MOF (Multiple Organ Failure)

Acute Pancreatitis
The Pathophysiology:
Interstitial edema within the pancreatic parenchyma

Necrosis of peripancreatic fat

Coagulation necrosis of glandular elements and surrounding fatty tissues

Necrotizing pancreatitis

Acute Pancreatitis
Activation of Pancreatic Enzymes:
Trypsin Kalikrein Phospholipase A2 Elastase Vasodilatation, capillary permeability Autodigestion of pancreatic tissues

Extravasation fluid into the 3rd space, DIC

Circulatory collapse, renal insufficiency, respiratory failure

Acute Pancreatitis
Conditions associated with acute pancreatitis:
Cholelithiasis Ethanol misuse Drugs Trauma Major abdominal surgery Cardiopulmonary bypass Hypercalcemia Hyperlipidemia Pancreatic tumors

Familial pancreatitis Vasculitis Ischaemic/embolism Pregnancy Organ transplantation Endstage renal failure Mycoplasma Viral infection.

Acute Pancreatitis
Drugs associated with pancreatitis:
a.

Definite association Azathioprine; 6-merkaptopurine; asparaginase; pentamidine; didanosine.

Probable Valproic acid; furosemide; hidrochlortiazide; sulphonamide; tetracycline; estrogen; paracetamol overdose; ergotamine overdose. Possible Corticosteroids; cyclosporine; methyldopa; metronidazole; erithromycin; cimetidine.

b.

c.

Acute Pancreatitis
Clinical Presentation:
Boring epigastric pain, poorly localized, radiates to the back.

Signs peritoneal irritation (DD: Acute ischemic of the bowel).

Nausea, vomiting, abdominal distention.

Acute Pancreatitis
RANSON criterias:
Initial 24 hours:

Subsequent 48 hours:
PaO2 <

Age > 55 y.o. Glucose > 200 mg/dl WBC > 16.000/ml LDH > 350 IU/L AST > 250 IU/L

60 mHg BUN > 8 mg/dl Ca < 8 mg/dl Base deficit > 4 meq/L Estimated fluid sequestration > 6L Fall in Hct>10%.

Mortality rate:
A. < 3 signs = 1% B. Three to four signs = 11%. C. Five to six signs = 33% D. > 6 signs = 100%.

Acute Pancreatitis
IMRIES criterias:
During first 24 hours: Age > 55 y.o. WBC > 15.109/L Blood glucose > 10 mmol/L Plasma urea > 16 mmol/L PaO2 < 18 Kpa PIasma Ca < 2 mmol/L PIasma Albumin < 32 g/L LDH > 600 IU/L AST/ALT > 100 IU/L.

Dx. Pancreatitis
Laboratory studies:
Serum Amylase
Uncomplicated Level rises within 2-12 hours after the onset of symptoms. The cutoff is 3 times than normal (35-118 IU/L) Peak level can be determined at 12-72 hours. Back to normal level in 2-3 days (one week) Persistent level >10 days complication like cyst, abscess. Sensitivity (75-92%); specificity (20-60%).

Dx. Pancreatitis
Laboratory studies:
Serum Lipase:
The serum level increases 2 times than normal (2,3 -20 IU/L). Level rises within 4-8 hours after the onset of symptoms. Back to normal level in 3-5 days. Decreases 8-14 days. Sensitivity (50-99%); specificity (86-100%). Better than amylase in alcoholic pancreatitis.

Dx. Pancreatitis
Laboratory studies:
Trypsinogen / elastase:
Human pancreatic juice:

Trypsinogen 19% of total protein Three trypsinogen isoenzymes Secreted by the acinal cells of pancreas Activated by enterokinase Active at pH 5,6, 1 mM Ca2+ Slow at pH 8, low Ca2+

Trypsinogen inhibition:
Pancreatic Secretory Trypsin Inhibitor (PSTI) Tumor Associated Trypsin Inhibitor (TATI)

Dx. Pancreatitis
Laboratory studies:
Expression of Trypsinogen:
outside the pancreas: small intestine, gastric mucosa, esophagus, stomach, lung, kidney, liver

Expression in Tumor:
Ca ovarii, Ca gaster, Ca colorectal, Ca pancreas, Ca esophagus, cholangicarcinoma, lung cancer, Ca prostat

Pancreatic tumor tubular pancreatic adenoCa

Dx. Pancreatitis
Laboratory studies:
Role of trypsinogen in pancreatic diseases:
Pancreatitis:
Better than amylase More accurate serum markers Trypsinogen 1 & 2 increase at 1 hr 5 days with the peak level at 6 hr Characteristic in biliary acute pancreatitis & alcohol induced pancreatitis

Cancer:
Pancreas tubular adenoma
Extra pancreas esophageal Ca Ca colorectal

Curve of pancreatic enzymes

amylase
IU/L

trypsin

lipase

2 hrs 4 hrs 8 hrs 12 hrs SIMPTOMS

72 hrs

3 days

7 days 14 days

Pancreatic Neoplasma
Diagnostic:
a) b) c) d) Computed Tomography (CT) Magnetic Resonance Imaging (MRI) Tumor Markers Cytologic

Tumor Markers
Cancer antigen (CA) 19-9
Pancreatic adenocarcinoma Concentration in cyst fluid - has not been established as a useful indicator - indicator for discriminating mucinous and non-mucinous cystic lesions. - elevated in malignant cystic lesions

Tumor Markers
Cancer antigen (CA) 72-4
Mucinous lesions: suggested that CA 72-4 is useful for identifying mucinous lesions Mucin like antigen that reflects the presence of a mucinous epithelium has been also used to dx mucinous lesions and cancers Amylase is not a tumor marker

Tumor Markers
Carcinoma Embryonic Antigen (CEA)
Antigen oncofetal

Could be found in: intestine, liver, pancreas

Elevated level: - colorectal cancer (early stage 40%, late stage 60%). - breast Ca, lungs Ca, ovarium Ca, stomach cancer, pancreas cancer.

Tumor Markers
Function of CEA:
1. Dx monitoring: every 3 months. 2. Rx monitoring: normal after 1-2 months after operation. 3. Prognosis: pre operative CEA < 10 mg/ml metastase post operative: decrease < 5 ng/L recidive