 Islet cells secrete at least 4 hormones

Pancreatic Function & into blood: insulin, glucagon, gastrin, &

Gastrointestinal Function somatostatin.

Introduction • Exocrine Component

• Gastrointestinal (GI) System  Produces digestive fluid rich with

 Comprises mouth, esophagus, stomach,
small & large intestines
 Digestion: process by which starches,
proteins, lipids, & nucleic acids are
degraded to molecules for absorption &
use in body
• Abdominal structures of the alimentary tract
enzymes in acinar cells, which line
pancreas & are connected by small
ducts
 Secretes about 1.5–2 L/day of fluid into
ducts that empty into duodenum
• Diagram of the pancreas and its relationship to
the duodenum

Pancreatic Fluid

• protein- rich,clear, colorless, and watery

• with an alkaline pH that can reach up to 8.3.

Pancreas • The bicarbonate and chloride concentrations
vary reciprocally
 Large gland involved in digestive process, but
lies outside of GI system • same concentrations of potassium and sodium
 Located behind peritoneal cavity across upper as serum
abdomen at level of 1st & 2nd lumbar
Pancreatic enzymes
vertebrae, 1–2 inches above umbilicus
 Composed of both endocrine & exocrine tissue (1) the proteolytic trypsin,
 Liver and pancreas- digestion enzymes chymotrypsin,
 pancreas is only second in size to the liver elastase,
collagenase,
 weighing about 70–105 g. It
leucine
Physiology of Pancreatic Function aminopeptidase,
and some
• Endocrine Component carboxypeptidases
(2) lipid-digesting lipase and lecithinase
 Smaller than exocrine component
enzymes
 Consists of islets of Langerhans: well- (3) carbohydrate- Pancreatic amylase
delineated, spherical or ovoid clusters splitting
composed of at least 4 different cell
types
Secretin and cholecystokinin
• Secretin is responsible for the production of
bicarbonate-rich and, therefore, alkaline
pancreatic fluid, which protects the lining of the
intestine from damage.
• Secretin is synthesized in response to the acidic
contents of the stomach reaching the
duodenum.
• It can also affect gastrin activity in the stomach.
• Secretin and cholecystokinin
• CCK, formerly called pancreozymin, in the
presence of fats or amino acids in the
duodenum, is produced by the cells of the
intestinal mucosa
• Responsible for release of enzymes from the
acinar cells by the pancreas into the pancreatic
fluid.
Diseases of the Pancreas
Cystic Fibrosis
 fibrocystic disease of the pancreas and
mucoviscidosis
 An inherited autosomal recessive disorder,
characterized by dysfunction of mucous &
exocrine glands throughout body
 Manifestations: intestinal obstruction
(newborn), excessive pulmonary infections
(childhood), pancreatogenous malabsorption
(adults)
 Causes ducts & acini to dilate & convert into
small cysts filled with mucus, preventing
secretions from reaching duodenum
Pancreatic Carcinoma
 4th most frequent form of fatal cancer; 5-year
survival rate <5%
 Most tumors arise as adenocarcinomas of
ductal epithelium.
 pain is a prominent feature of the disease.
 jaundice, weight loss, anorexia, and nausea
Islet cell tumors
• Tumors in Beta cells
• Hyperinsulinism
• Gastrinomas
• Pancreatic cell tumors, which overproduce
gastrin,
• they cause Zöllinger-Ellison syndrome and can
be duodenal in origin.
• watery diarrhea, recurring peptic ulcer, and
significant gastric hypersecretion and
hyperacidity
Pancreatitis
 Inflammation of pancreas
 Caused by autodigestion of pancreas as a result
of reflux of bile or duodenal contents into
pancreatic duct
 Pathologic changes include acute edema,
cellular infiltration, & intrahepatic &
extrahepatic pancreatic fat necrosis.
• Results
 All 3 conditions can result in severely
diminished pancreatic exocrine
function, compromising digestion &
absorption.
 Malabsorption syndrome: abdominal
bloating & discomfort, frequent passage
of bulky, malodorous feces, & weight
loss
Tests of Pancreatic Function
1. Secretin/CCK Test
 Direct determination of exocrine
secretory capacity of pancreas
 Involves intubation of duodenum
without contamination by gastric fluid,
which would neutralize any bicarbonate
 Performed after a 6-hour or overnight
fast
 Pancreatic secretion is stimulated by
secretin followed by CCK.
  Secretions are collected for 30, 60, or
80 minutes after administration of
stimulants.
 pH, secretory rate, enzyme activities,
bicarbonate are measured.
2. Fecal Fat Analysis
• Fecal lipids are derived from 4 sources:
1. Unabsorbed ingested lipids
2. Lipids excreted into intestine
3. Cells shed into intestine
4. Metabolism of intestinal bacteria
• Qualitative screening: Sudan staining
 Neutral fats & other lipids stain
yellow-orange to red with
Sudan III because dye is more
soluble in lipid.
 Increases in fats & undigested
meat fibers indicate
steatorrhea of pancreatic
origin.
• Quantitative screening: Gravimetric
method
 Entire fecal specimen is
emulsified with water.
 An aliquot is acidified to
convert all fatty acid soaps to
free fatty acids.
 Then most lipids are extracted
into petroleum ether & ethanol.
 After evaporation of organic
solvents, lipid residue is
weighed.
3. Sweat Electrolyte Determinations
 Measurement of sodium & chloride
concentration in sweat is most useful
test for diagnosis of cystic fibrosis.
 In children, levels of sweat sodium &
chloride above 60 mmol/L are
diagnostic.
 In adults, levels above 80 mmol/L are
diagnostic.
 Sweat collection involves pilocarpine
administration by iontophoresis.
4. Serum Enzymes
 Amylase
Enzyme most commonly used
for detecting pancreatic disease
Particularly useful in diagnosis
of acute pancreatitis
Serum levels increase within
hours of onset of disease, peak
in about 24 hours, & return to
normal within 3–5 days.
i. Renal clearance of amylase is
useful measure for detecting
minor or intermittent increases
in serum concentrations.
 Lipase
i. Some physicians consider lipase
more sensitive than amylase.
Physiology and Biochemistry of Gastric Secretion
Stimuli Triggering Gastric Secretion
 Neurologic impulses from brain transmitted by
vagal nerves
 Distention of stomach with food or fluid
 Contact of protein breakdown products with
gastric mucosa
 Hormone gastrin (most potent)
Inhibitors of Gastric Secretion
 High gastric acidity, which decreases release of
gastrin by G cells
 Gastric inhibitory polypeptide, secreted by K
cells
 Vasoactive intestinal polypeptide, produced by
H cells
Clinical Aspects of Gastric Analysis  Materials enter jejunum & ileum, where 1.5
L of secretion is added; only ~1.5 L of fluid
 Purposes of Gastric Analysis
material reaches cecum.
o To detect hypersecretion characteristic of
 Mucosal folds, villi, & microvilli in 20-foot-
Zollinger-Ellison syndrome
long small intestine allow massive
o Occasionally, to evaluate pernicious anemia in absorption.
adults
 Large intestine absorbs water & stores feces
o Rarely, to aid in determining type of surgical before defecation.
procedure required for ulcer treatment

 Stimulus for Gastric Analysis

Clinicopathologic Aspects of Intestinal Function
Pentagastrin is now used as stimulus to
Diseases That Cause Malabsorption
gastric secretion.
 Tropical & nontropical or celiac sprue
Tests of Gastric Function
 Whipple’s disease
1. Measuring Gastric Acid in Basal, Maximal
Secretory Tests  Crohn’s disease
 After overnight fast, performed as 1-hour basal  Primary intestinal lymphoma
test followed by 1-hour stimulated test after
pentagastrin administration  Small intestinal resection

 In stimulated-secretion specimens, ability of  Intestinal lymphangiectasia

stomach to secrete against a hydrogen ion  Ischemia
gradient is determined by measuring pH.
 Amyloidosis
 Gastrin response to secretin stimulation may be
used to investigate patients with mildly  Giardiasis
elevated serum gastrin levels.

 In this test, pure porcine secretin is injected &

Tests of Intestinal Function
gastric levels are collected at 5-minute intervals
for next 30 minutes. 1. Lactose Tolerance Test

2. Plasma Gastrin  Disaccharidases, lactase, & sucrase are

produced by mucosal cells of small
1. Invaluable in diagnosing Zollinger-
intestine.
Ellison syndrome
 Acquired deficiencies of lactase are
Intestinal Physiology
common in adults.
Digestion
 Affected patients experience abdominal
 Predominantly a function of small intestine discomfort, cramps, & diarrhea after
ingesting milk or milk products.
 Necessary for absorption to occur for most
large molecules  About 10–20% of whites & 75% of
African Americans are affected.
 Process:
 Lactose tolerance test established this
 7–10 L of ingested water & food & secretion diagnosis but is subject to many false-
from salivary glands, stomach, pancreas, & positive & false-negative results.
biliary tract enters duodenum.
  It has been replaced largely by  Negative nitrogen balance, decreased
hydrogen breath testing. serum proteins & albumin

2. D-Xylose Absorption Test  Deficiencies of fat-soluble vitamins A, D,

E, & K
 D-Xylose: a pentose sugar ordinarily not
present in blood  Deficiencies of vitamin-K dependent
coagulation factors
 Pentose sugars are absorbed unaltered
in proximal small intestine, do not  Anemia, diminished iron & calcium
require intervention of pancreatic lytic absorption
enzymes.
 Decreased sodium & potassium levels,
 Ability to absorb D-xylose helps dehydration
differentiate malabsorption of intestinal
 Decreased/flat blood concentration
etiology from that of exocrine
curves in glucose, lactose, & sucrose
pancreatic insufficiency.
tolerance tests
 Process

i. After overnight fast, patient

voids & drinks D-xylose
solution.

ii. Patient drinks equivalent

amount of water during next
hour.

iii. Urine is collected for 5 hours

after ingestion; blood specimen
is collected at 2 hours.

3. Serum Carotenoids

 Various yellow to orange or purple

pigments widely distributed in animal
tissue

 Synthesized by many plants & impart a

yellow color to some vegetables & fruits

 Major carotenoids in human serum are

lycopene, xanthophyll, & beta-carotene
(precursor of vitamin A).

 Are fat-soluble & are absorbed in small

intestine with lipids

 Malabsorption of lipids results in serum

concentration of carotenoids lower
than reference range of 50–250 mg/dL.

4. Other Tests of Intestinal Malabsorption

 Diminished appetite & dietary intake

 Body wasting or cachexia