Must Know for Pancreatic and gi function docx

Pancreatic Function and Gastrointestinal Function
Gastrointestinal (GI) system
•
Mouth
•
Esophagus
•
Stomach
•
Small intestine – digestion
•
Large intestine
Physiology of Pancreatic Function
Pancreas
-a large gland that is involved in the digestive process, but located outside of the GI system.
Endocrine (hormone-releasing) component
• smaller than the exocrine component
• islets of Langerhans
o Insulin
o Glucagon
o Gastrin
o somatostatin
Exocrine pancreatic (enzyme-secreting) component
• Larger than endocrine component
• Pancreatic Acinar cells
• secretes about 1.5 to 2 L/d of digestive enzyme-rich fluid
Pancreatic fluid
• clear, colorless, and watery
• protein-rich liquid
• alkaline pH that can reach up to 8.3
• high concentration of sodium bicarbonate
• same concentrations of potassium and sodium as serum
Digestive enzymes (proenzymes)
• trypsin, chymotrypsin, elastase, collagenase, leucine aminopeptidase, and some carboxypeptidases
• lipase and lecithinase
• amylase
• nucleases
Pancreatic activity
-is under both nervous and endocrine control.
Vagus nerve-
can cause a small amount of pancreatic fluid secretion when food is smelled or seen, and these
secretions may increase as the bolus of food reaches the stomach.
Secretin-
is responsible for the production of bicarbonate-rich and, therefore, alkaline pancreatic fluid,
which protects the lining of the intestine from damage.
CCK-
(cholecystokinin formerly called pancreozymin) is produced by the cells of the intestinal mucosa
and is responsible for release of enzymes from the acinar cells by the pancreas into the pancreatic
fluid.
Diseases of the Pancreas
• Cystic fibrosis
-autosomal recessive
-relatively common
-dysfunction of mucous and exocrine glands
Manifestations:
-Intestinal obstruction of the new-born
-Excessive pulmonary infections in childhood
-Pancreatogenous malabsorption in adults
-caused by gene CFTR on chromosome 7
-most common genetic disorder in Brittany
in Western France
• Pancreatic carcinoma
– fourth most frequent form of fatal cancer
– common in males than females and in African Americans than whites
– most pancreatic tumors arise as adenocarcinomas of the ductal epithelium
If the tumor arises in the body or tail of the pancreas, detection does not often occur until an advanced stage of the disease
because of its central location and the associated vague symptoms. Cancer of the head of the pancreas is usually detected
earlier because of its proximity to the common bile duct.
Signs:
-jaundice
-anorexia
-weight loss
-nausea
Islet cell tumors
– affect the endocrine capability of the pancreas
– occurs in beta cells
– hyperinsulinism
Gastrinomas
– pancreatic cell tumors that overproduce gastrin
– Zöllinger- Ellison syndrome
associated with:
-watery diarrhea
-gastric hypersecretion and hyperacidity
-recurring peptic ulcer
Pancreatic cell glucagon-secreting tumors are rare; the hypersecretion of glucagon is associated with diabetes mellitus.
• Pancreatitis
– commonly occurs in midlife
-inflammation of the pancreas
-autodigestion of the pancreas
Pathologic changes:
-acute edema: retroperitoneal space
-cellular infiltration: necrosis of the acinar cells
-intrahepatic and extrahepatic pancreatic fat necrosis
Classification:
-acute: no permanent damage to the pancreas
-chronic: irreversible injury
-relapsing/recurrent: can also be acute or chronic
associated with:
-alcohol abuse
-hyperlipoproteinemia
-biliary tract diseases: gallstones
-hyperparathyroidism
Etiologic factors associated with acute pancreatitis include:
-mumps
-gallstones
-biliary tract disease
-pancreatic tumors
– tissue injury
-atherosclerotic disease
-shock
-pregnancy
-hypercalcemia
-hereditary pancreatitis
Immunologic factors:
-postrenal transplantation
-hypersensitivity
Symptoms of acute pancreatitis:
-severe abdominal pain
Etiologic factors associated with chronic pancreatitis include:
-chronic excessive alcohol consumption
Laboratory findings:
– increased amylase, lipase, triglycerides, and hypercalcemia
– hyperparathyroidism
– hypocalcemia and hypoproteinemia
– shift to the right in ODC
Failure to digest or absorb fats, known as steatorrhea, renders a greasy appearance to feces (more than 5 g of fecal fat per 24
hours).
Malabsorption syndrome
– typically involves abnormal digestion or absorption of proteins, polysaccharides, carbohydrates, and other
complex molecules, as well as lipids.
– severely deranged absorption and metabolism of electrolytes, water, vitamins (particularly fat-soluble
vitamins A, D, E, and K), and minerals.
– can be caused by biliary obstruction
– can involve a single substance:
•
vitamin B12
•
lactose
Tests of Pancreatic Function
Depending on etiology and clinical picture, pancreatic function may be suspect when there is evidence of increased amylase
and lipase.
Laboratory tests
• Pancreatic function
-detection of malabsorption (e.g., examination of stool for excess fat, d-xylose test, and fecal fat analysis)
-tests measuring other exocrine function (e.g., secretin, CCK, fecal fat, trypsin, and chymotrypsin)
-tests assessing changes associated with extrahepatic obstruction (e.g., bilirubin)
-endocrine-related tests (e.g., gastrin, insulin, and glucose)
• Pancreatic fluid
-measurement of the total volume of pancreatic fluid
-measurement of amount/concentration of bicarbonate and enzymes
Stimulation
-predescribed meal or administration of secretin, which allows for volume and bicarbonate evaluation, or secretin
stimulation followed by CCK stimulation, which adds enzymes to the pancreatic fluid evaluation.
• Cytologic examination of the fluid
The sweat test, used for screening cystic fibrosis, is not specific for assessing pancreatic involvement but, when used along with
the clinical picture at the time of testing, can provide important diagnostic information.
Pancreatic function tests
• Secretin/CCK Test
Direct determination of the exocrine secretory capacity of the pancreas. The test involves intubation of the
duodenum without contamination by gastric fluid, which would neutralize any bicarbonate.
The test is performed after a 6-hour or overnight fast. Pancreatic secretion is stimulated by intravenously administered
secretin in a dose varying from 2 to 3 U/kg of body weight, followed by CCK administration. If a simple secretin test is desired,
the higher dose of secretin is given alone.
Pancreatic secretions are collected variously for 30, 60, or 80 minutes after administration of the stimulants, either as 10minute specimens or as a single, pooled collection. The pH, secretory rate, enzyme activities (e.g., trypsin, amylase, or lipase),
and amount of bicarbonate are determined.
Bicarbonate excreted per hour Normal Values:
Males – 15 mmol/L
Females – 12 mmol/L
average flow of 2 mL/kg
↓Pancreatic flow and ↑enzyme concentrations – pancreatic obstruction
↓Bicarbonate and enzyme concentrations – cystic fibrosis, chronic pancreatitis, pancreatic cysts, calcification, and edema of
the pancreas
Fecal Fat Analysis
-Fecal lipids are derived from four sources:
•
_____________________________
•
_____________________________
•
_____________________________
•
_____________________________.
-Patients on a lipid-free diet still excrete ___ g of lipid in the feces in a 24-hour period.
-Even with a lipid-rich diet, the fecal fat does not normally exceed about __g in a 24-hour period.
-Normal fecal lipid is composed of about 60% fatty acids; 30% sterols, higher alcohols, and carotenoids; 10% triglycerides; and
small amounts of cholesterol and phospholipids.
-Although significantly increased fecal fat can be caused by biliary obstruction, severe steatorrhea is usually associated with
exocrine pancreatic insufficiency or disease of the small intestine.
Qualitative Screening Test for Fecal Fat
fat-soluble stains
•
Sudan III
•
_______________________
•
_______________________
•
Sudan IV
•
Oil Red O
•
Nile blue sulfate
Sudan Staining for Fecal Fat
-Neutral fats (triglycerides) and many other lipids stain yellow-orange to red with Sudan III because the dye is much more
soluble in lipid than in water or ethanol. Free fatty acids do not stain appreciably unless the specimen is heated in the
presence of the stain _____________.
-The slide may be examined warm or cool and the number of fat droplets assessed. As the slide cools, the fatty acids
crystallize out in long, colorless, needle-like sheaves.
– Detection of meat fiber is accomplished by athird aliquot of fecal sample mixed on the slide with 10% alcohol and a solution
of eosin stained for 3 minutes. The meat fiber should stain as rectangular cross-striated fibers.
-Splitting the sample and detecting neutral fats, fatty acids, and undigested meat fibers can provide diagnostic information.
Increases in fats and undigested meat fibers are indicative of patients with steatorrhea of pancreatic origin. A representative
fecal specimen is used for analysis.
Quantitative Fecal Fat Analysis
-The definitive test for steatorrhea is the quantitative fecal fat determination, usually on a ___________, although the
collection period may be increased to up to 5 days.
-Traditional methods for fecal fat determination _____________________. Newer methods involve the use of infrared and
nuclear magnetic resonance spectroscopy.
Gravimetric Method for Fecal Fat Determination
-fatty acid soaps are converted to free fatty acids, followed by extraction of most of the lipids into an organic solvent, which is
then evaporated so that the lipid residue can be weighed.
-The entire fecal specimen is emulsified with water. An aliquot is acidified to convert all fatty acid soaps to free fatty acids,
which are then extracted with other soluble lipids into petroleum ether and ethanol. After evaporation of the organic
solvents, the lipid residue is weighed. All feces for a 3-day period are collected in tared containers. The containers must not
have a wax coating. The specimen must be kept refrigerated
-Patients must not ingest castor oil, mineral oil, or other oily laxatives and must not use rectal suppositories containing oil or
lipid for 2 days before the test and during the test.
Sweat Electrolyte Determinations
-Measurement of the sodium and chloride concentration in sweat is the most useful test for the diagnosis of cystic fibrosis.
-Significantly elevated concentrations of both ions occur in more than 99% of affected patients. __________ in sweat sodium
and chloride are diagnostic of cystic fibrosis in children. Even in adults, no other condition causes increases in sweat chloride
and sodium _________. Sweat potassium is also increased, but less significantly so, and is not generally relied on for
diagnosis.
-Sweat electrolyte determinations do not distinguish heterozygote carriers of cystic fibrosis from normal homozygotes.
•
_____________________ Iontophoresis Technique
•
_____________administration by iontophoresis was reported as an efficient method for sweat collection
and stimulation. Iontophoresis uses an electric current that causes ________ to migrate into a limited skin
area, usually the inside of the forearm, toward the negative electrode from a moistened pad on the positive
electrode. A collection vessel is then applied to the skin. The sweat is then analyzed for chloride. For
confirmation, the test should be repeated
Serum Enzymes-Amylase is the serum enzyme most commonly relied on for detecting pancreatic disease. It is not, however, a function test.
Amylase is particularly useful in the diagnosis of acute pancreatitis, in which significant increases in serum concentrations
occur in about 75% of patients.
-Typically, amylase in serum increases within a few hours of the onset of the disease, reaches a peak in about 24 hours, and
because of its clearance by the kidneys returns to normal within 3 to 5 days, often making urine amylase a more sensitive
indicator of acute pancreatitis. The magnitude of the enzyme elevation cannot be correlated with the severity of the disease-Determination of the renal clearance of amylase is useful in detecting minor or intermittent increases in the serum
concentration of this enzyme. To correct for diminished glomerular function, the most useful expression is the ratio of
amylase clearance to creatinine clearance, as follows:
% Amylase clearance
UA
= 100 x
Clearance
SC
x
(Eq. 28-1)
SAUC
where UA is urine amylase, SA is serum amylase, SC is serum creatinine, and UC is urine creatinine.
-Normal values are less than 3.1%. Significantly increased values, averaging about 8% or 9%, occur in acute pancreatitis but
may also occur in other conditions, such as burns, sepsis, and diabetic ketoacidosis.
Physiology and Biochemistry of Gastric Secretion
-Gastric secretion occurs in response to various stimuli:
•
Neurogenic impulses from the brain transmitted by means of the ______ (e.g., responses to the sight, smell, or
anticipation of food)
•
Distention of the stomach with food or fluid
•
Contact of protein breakdown products, termed _______ with the gastric mucosa
•
The hormone _______ is the most potent stimulus to gastric secretion; it is secreted by specialized G cells in the
gastric mucosa and the duodenum in response to vagal stimulation and contact with secretagogues.
-Inhibitory influences include high gastric acidity, which decreases the release of gastrin by the gastric G cells. Gastric
inhibitory polypeptide is secreted by K cells in the middle and distal duodenum and proximal jejunum in response to food
products such as fats, glucose, and amino acids. Vasoactive intestinal polypeptide, produced by H cells in the intestinal
mucosa, directly inhibits gastric secretion, gastrin release, and gastric motility.
-Gastric fluid has a high content of hydrochloric acid, pepsin, and mucus. Hydrochloric acid is secreted against a hydrogen ion
gradient as great as 1 million times the concentration in plasma (i.e., gastric fluid can reach a pH of 1.2 to 1.3 under
conditions of augmented or maximal stimulation).
-_____ refers to a group of relatively weak proteolytic enzymes, with pH optima from about 1.6 to 3.6, that catalyze all native
proteins except mucus. The most important component of gastric secretion in terms of body physiology is ________, which
greatly facilitates the absorption of vitamin B12 in the ileum.
Aspects of Gastric Analysis
•
Gastric analysis is used in clinical medicine mainly for the following purposes:
•
Gastric analysis was once widely used in clinical medicine but has now been largely replaced by fiberoptic endoscopy
and improved radiologic procedures.
•
Gastric analysis is used clinically mainly to detect hypersecretion characteristics of the _____________. This
syndrome involves a gastrin-secreting neoplasm, usually located in the pancreatic islets, and exceptionally high
plasma gastrin concentrations. ____________________________________ (i.e., the stomach is not really in the basal
state but rather is pathologically stimulated by the high plasma gastrin level).
•
•
Gastric analysis is also used occasionally to evaluate ____________ in adults. Gastric atrophy is present in this
condition, and the stomach fails to secrete intrinsic factor, which binds to vitamin B12 to prevent its degradation by
gastric acid. The pH of gastric fluid in this condition typically does not fall below 6, even with maximum stimulation.
Rarely, gastric analysis may aid in determining the type of surgical procedure required for ulcer treatment.
Normal gastric fluid is translucent, pale gray, and slightly viscous and often has a faintly acrid odor. Residual volume
should not exceed 75 mL. Residual specimens occasionally contain flecks of blood or are green, brown, or yellow from
reflux of bile during the intubation procedure. The presence of food particles is abnormal and indicates obstruction.
Tests of Gastric Function Measuring Gastric Acid in Basal and Maximal Secretory Tests
After an overnight fast, gastric analysis is usually performed as a 1-hour basal test, followed by a 1-hour stimulated test
subsequent to pentagastrin administration (6 μg/kg subcutaneously)
Gastric peptic ulcer:
N secretory volume and acid output
Duodenal peptic ulcer:
↑ secretory volume (basal and maximal secretory tests)
Measuring Gastric Acid
In stimulated secretion specimens, the ability of the stomach to secrete against a hydrogen ion gradient is determined by
measuring the pH
The total acid output in a timed interval is determined from the titratable acidities and volumes of the component specimens.
1.
2.
After intubation, the residual secretion is aspirated and retained.
Secretion for the subsequent 10 to 30 minutes is discarded to allow for adjustment of the patient to the intubation
procedure. Specimens are ordinarily obtained as 15-minute collections for a period of 1 hour.
The gastrin response to intravenous secretin stimulation may be used to investigate patients with mildly elevated serum
gastrin levels.
3.
In this test, pure porcine secretin is injected intravenously
4.
Gastrin levels are collected at 5-minute intervals for the next 30 minutes.
–
Zöllinger-Ellison syndrome
the gastrin level increases at least 100 pg/mL over the basal level
–
Ordinary peptic ulceration, achlorhydria
a slight decrease in gastrin concentration
Report: Volume, pH, titratable acidity, calculated acid output, total volume and acid output for each tests
Gastric acid output
There is considerable variation in gastric acid output among healthy subjects in both the basal and maximal secretory tests.
In the basal test,
most healthy subjects secrete 0 to 6 mmol of acid in a total volume of 10 to 100 mL.
In the maximal 1-hour test, using histamine or pentagastrin as the stimulus,
Male −
40 mmol of acid (in a total volume of 40 – 350 mL)
Female/Elderly −
6 months
Healthy adults −
Abnormal
−
−
15 mg/dL
−
at 1 hour, blood concentration
−
30 mg/dL
4g
−
5-hour period