[email protected] || 1 st semester, AY 2011-2012 8 - Gastrointestinal and Exocrine Pancreatic Function Pancreatic Endocrine Functions • To synthesize hormones such as glycogen, insulin and gastrin • Originate from a group of cells called islets located in an area islets of Langerhans • Islet cells contain beta, alpha and delta cells which is responsible for the production of hormones (glycogen, insulin and gastrin) • Islet cells are surrounded by acinar cells which are responsible for the production of exocrine digestive enzymes such amylase and lipase Pancreatic exocrine function tests • Diagnosis of diseases such malabsorption and cystic fibrosis • Tests useful in the diagnosis – B-carotine test of pancreatic malabsorption process – Vitamin B12 test – Sweat chloride test Endocrine Functions from the Islets of Langerhans Cell Production Action Outcome Alpha Cells Glucagon Glycogenolysis Gluconeogenesis Glucose Glucose Beta Cells Preinsulin Insulin Glucose uptake Glucose Delta Cells Gastrin Digestion Gastric acid Exocrine Functions from the Acinar Cells Cell Production Enzymes Digestive Stimulation Acinar Cells Enzymes and proteolytic enzymes precursors Trypsin α-Amylase Cholesterol esterase Phospholipase A Lipase Protein Starch Cholesterol esters Phospholipids Triglycerides Common Gastrointestinal disorders • Gastric disorders – Peptic Acid disease • Pancreatic disorders – Macro amylassemia – Acute pancreatitis – Chronic pancreatitis – Cystic fibrosis • Intestinal disorders – Chronic diarrhea – HIV-related diarrhea – Nosocomial diarrhea Gastric Disorders Peptic Acid Disorders • Main cause of duodenitits and duodenal ulcers: Helicobacter pylori • Associated conditions: – Type B chronic antral gastritis – Gastric ulcers – Non ulcer dyspepsia – Gastric carcinoma Tests utilized for Peptic Acid disorders • H. pylori test – Ability of organism to produce urease • Radioactive and nonradioactive breath hydrogen ion tests • Enzyme-linked immunosorbent Urease-based chemical tests • Specimen: Fresh biopsy specimens • Principle: – Bacterial urease splits the urea producing ammonia • End results: – Change of pH affect the color indicator Other causes of extensive peptic acid disease • Hypersecretory states – (in the absence of H. pylori and the use NSAIDS) – Failure to respond to the usual dose of histamine 2 (H2) receptor blocking agents – Proton pump inhibitor • Gastric levels with and without secretion stimulation – Zollinger-Ellison syndrome * Serum gastrin levels greater than 150 ng/L (normal <100 ng/L) especially with simultaneous gastric pH value of <3 are highly suggestive of gastrinoma Pancreatic Disorders Macroamylasemia • A condition of persistently elevated serum amylase activity with no apparent clinical symptoms of pancreatic disorder • Attibuted to the presence of an amylase macromolecule complex whose larger size precludes its excretion in urine • Is a circulatory complex of normal amylase linked to an immunoglobulin (IgA and IgG) Differential Diagnosis of Hyperamylasemia and Macroamylasemia CONDITION SERUM AMYLASE SERUM LIPASE URINARY AMYLASE C am :C cr SERUM AMACRO- AMYLASE Pancreatic hyperamylasemia ↑ ↑ ↑ ↑ - Salivary hyperamylasemia ↑ N ↓ / N ↓ / N - Macroamylasemia type 1 ↑ N ↓ Very ↓ ↑ Macroamylasemia type 2 ↑ N ↓ / N ↓ M Macroamylasemia N N N ↓ / N T N - Normal M - Moderate T - Trace C am :C cr = amylase clearance:creatinine clearance ratio = (urinary amylase/serum amylase) X (serum creatinine/urinary creatinine)
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08 - Gastrointestinal and Exocrine Pancreatic Function
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8 - Gastrointestinal and Exocrine Pancreatic Function
Pancreatic Endocrine Functions
• To synthesize hormones such as glycogen, insulin and gastrin
• Originate from a group of cells called islets located in an area islets of Langerhans
• Islet cells contain beta, alpha and delta cells which is responsible for the production of hormones (glycogen, insulin and gastrin)
• Islet cells are surrounded by acinar cells which are responsible for the production of exocrine digestive enzymes such amylase and lipase
Pancreatic exocrine function tests
• Diagnosis of diseases such malabsorption and cystic fibrosis
• Tests useful in the diagnosis – B-carotine test of pancreatic malabsorption
process
– Vitamin B12 test – Sweat chloride test
Endocrine Functions from the Islets of Langerhans Cell Production Action Outcome Alpha Cells
Glucagon Glycogenolysis Gluconeogenesis
Glucose
Glucose
Beta Cells
Preinsulin Insulin
Glucose uptake Glucose
Delta Cells
Gastrin Digestion Gastric acid
Exocrine Functions from the Acinar Cells Cell Production Enzymes Digestive
Stimulation Acinar Cells
Enzymes and proteolytic enzymes precursors
Trypsin α-Amylase Cholesterol esterase
Phospholipase A Lipase
Protein Starch Cholesterol esters Phospholipids
Triglycerides
Common Gastrointestinal disorders
• Gastric disorders
– Peptic Acid disease
• Pancreatic disorders
– Macro amylassemia – Acute pancreatitis
– Chronic pancreatitis
– Cystic fibrosis
• Intestinal disorders
– Chronic diarrhea
– HIV-related diarrhea
– Nosocomial diarrhea
Gastric Disorders
Peptic Acid Disorders
• Main cause of duodenitits and duodenal ulcers: Helicobacter pylori
• Associated conditions: – Type B chronic antral gastritis
– Gastric ulcers
– Non ulcer dyspepsia
– Gastric carcinoma
Tests utilized for Peptic Acid disorders
• H. pylori test
– Ability of organism to produce urease • Radioactive and nonradioactive breath hydrogen ion
tests
• Enzyme-linked immunosorbent
Urease-based chemical tests
• Specimen: Fresh biopsy specimens
• Principle:
– Bacterial urease splits the urea producing ammonia
• End results: – Change of pH affect the color indicator
Other causes of extensive peptic acid disease
• Hypersecretory states
– (in the absence of H. pylori and the use NSAIDS)
– Failure to respond to the usual dose of histamine 2 (H2) receptor blocking agents
– Proton pump inhibitor • Gastric levels with and without secretion stimulation
– Zollinger-Ellison syndrome
* Serum gastrin levels greater than 150 ng/L (normal <100 ng/L) especially with simultaneous gastric pH value of <3 are highly suggestive of gastrinoma
Pancreatic Disorders
Macroamylasemia
• A condition of persistently elevated serum amylase activity with no apparent clinical symptoms of pancreatic disorder
• Attibuted to the presence of an amylase macromolecule complex whose larger size precludes its excretion in urine
• Is a circulatory complex of normal amylase linked to an immunoglobulin (IgA and IgG)
Differential Diagnosis of Hyperamylasemia and Macroamylasemia CONDITION
SERU
M
AMYL
ASE
SE
RUM
LI
PASE
U
RIN
ARY
AMYL
ASE
C am
:Ccr
SERU
M
AMAC
RO-
AMYL
ASE
Pancreatic hyperamylasemia
↑ ↑ ↑ ↑ -
Salivary hyperamylasemia
↑ N ↓ / N ↓ / N -
Macroamylasemia type 1
↑ N ↓ Very ↓
↑
Macroamylasemia type 2
↑ N ↓ / N ↓ M
Macroamylasemia N N N ↓ / N T
N - Normal M - Moderate
T - Trace
Cam:Ccr = amylase clearance:creatinine clearance ratio = (urinary amylase/serum amylase) X (serum creatinine/urinary creatinine)
• Serum amylase level appear first 2-12 hours after the onset of acute pancreatitis reaches its peaks at 48 hours and return to normal within 3-5 days
• Serum Lipase
– Derived from pancreatic acinar cells
– Disease pattern
• Rises 4-8 hours after the onset of acute panceatitis (earlier than serum amylase), reaches its peak at 24 hours and last longer in the serum 8-14 days
– More sensitive and more specific than serum amylase
For Etiologic usefulness
• SGPT/SGOT
• Lipase/amylase
• Carbohydrate deficient transferin (CDT)
For severity of disease
• Trypsinogen Activation peptide (TAP)
• Hematocrit • C-reactive protein (CRP)
Chronic Pancreatitis
• Marked by progressive destruction of islet cells and acinar tissue (Acinar tissue is responsible for maldigestion associated with chronic pancreatitis due to loss of enzyme secretion responsible for digestion of food stuff)
• Routine laboratory testing is of little value although amylase and lipase maybe elevated however the absence of these enzyme in the serum does not rule out chronic pancreatitis
Clinical diagnosis of chronic pancreatitis depends on
• Finding of structural abnormalities in the ductal anatomy found on imaging
• The simplest method of functional testing of the pancreas
– Assessment of the presence of fat in the stool
– Serum trypsinogen assays can be done but can be useful only when the values are below 20 ng/mL but the values are only to be low in patients with advanced disease typically when steatorrhea is already present)
– Fecal elestase can be used in the diagnosis because of inadequate delivery of fecal elastase in the duodenum
Intestinal Disaccharidase Deficiency in these disorders:
• Unhydrolyzed and unabsorbed carbohydates are fermented by intestinal bacteria, producing gas, lactic acid. Normally, absorption of digested carbohydrates is rapid and fairly complete in the proximal small intestine
• Unhydrolyzed dissacharides or unabsorbed monosaccharides due to deficiencies in transport are osmotically active which causes secretion of water and electrolytes into the small intestines