08 - Gastrointestinal and Exocrine Pancreatic Function
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Transcript of 08 - Gastrointestinal and Exocrine Pancreatic Function
[email protected] || 1st 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
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)
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Acute Pancreatitis
• Serum Amylase
– Universal laboratory test
– Derived from pancreatic acinar cells
– Disease pattern
• 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
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Cystic Fibrosis
• Autosomal rescessive disease • Characterized by abnormal secretion from the various
exocrine glands of the body including the: • Pancreas
• Salivary glands
• Peritracheal glands
• Peribronchial glands
• Peribronciolar glands
• Sweat glands
• Mucosal glands of the small bowel • Bileducts
• Complications (major clinical problems)
• Laboratory diagnosis
• Sweat testing
• Demonstration of increased sodium and chloride in the sweat
• Testing should be done on two occassions with chloride concentration of over 60 mmoL/L of sweat are diagnostic
Intestinal disorders
• Chronic diarrhea
• HIV related diarrhea
• Nosocomial diarrhea
Testing for Malabsorption and Cystic Fibrosis Testing for Malabsorption Tripeptide Hydrolysis Test
Decreased para-aminobenzoic acid results suggest pancreatic insufficiency
Fecal Fat Values 5-10g% suggest malabsorption Values > 10 g% suggest maldigestion
14C-Triolein Breath
Decreased 14CO2 in expired air suggsts fat malabsorption
D-Xylose Absorption
Values below reference ranges suggest little to no absorption capacity of the proximal small bowel mucosa
Vitamin B12 Malabsorption
Patients who excrete < 7% are suspected to have pernicious anemia
Β-Carotine Decreased levels are seen in patients with malabsorption and/or malnutrition
Testing for Cystic Fibrosis Sweat Chloride Increased levels are diagnostic of cystic
fibrosis
FECALYSIS
• Analysis of stool contents
– Collection of Feces
– Examination of feces
• Macroscopic examination
• Microscopic examination
Collection of Feces
Adult Collection
• 24-hour stool collection
• Method: A. Ingestion of dye (0.3 g) at the beginning and
charcoal at the end of collecting period
B. Use of inert, non absorbable stool markers • Collected over a period of 3 days
• Weight / no. of days of collection
• Begin : Carmine dye(0.3g)
• End: charcoal (1 g)
• Start collecting stool at the appearance of the dye and end at the appearance of the charcoal
Pediatric collection
• Method: – Use of a thick-walled glass tube, which is
lubricated by clipping into water and then inserted into the young child rectum
• Thick-walled glass tube lubricated with water
• Core of feces can be obtained
• Poked out with applicator stick
Examination of Feces
Inspection
• Parasitic infestation
• Obstructive jaundice
• Diarrhea
• Malabsorption • Rectosigmoidal obstruction
• Dysentery
• Ulcerative colitis
• GIT bleeding
Macroscopic characteristics
Quantity
• 100 to 200 gms/day
Form
• Abnormal Forms – Diarrheal (watery)
– Steatorrhea (large amount, foul-smelling gray stool floats on water)
– Constipation (scybala)
Diarrhea
• If the amount of fluid entering or secreted into the large intestine exceeds the capacity for absorption, diarrhea results
• Normally: Ileum large intestine (500 -1500 ml of fluid) stool (150 ml)
Classification of Diarrhea
• Inflammatory/Exudative – Immune-mediated injury of GI mucosa
– Inflammatory bowel disease
– Crohn’s disease
– Ulcerative colitis
– Infectious
– Salmonella
– Shigella – Campylobacter
– Eteroinvasive E. coli – Yersinia enterocolitica – HIV enteropathy
• Secretory – Increased secretion of water and
electrolytes into the GI tract lumen
• Enteric infection
• Salmonella
• Shigella • Enterotoxigenic E. coli • V. cholera
• Staphylococci • Clostridia
• Protozoan
• Rotavirus
• Hormone mediated
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• Osmotic
– Non-absorbed substances retain water in the GI tract lumen
– Maldigestion- Incomplete breakdown of protein, lipid,and/or carbohydrates
– Pancreatic insufficiency: • Chronic pancreatitis, cystic fibrosis,
obstruction at ampulla of Vater, pancreatic adenocarcinoma, somatostatinoma
– Carbohydrate intolerance: deficiency on
• Lactase, isomaltase-sucrase,and trehalase enzymes
– Others: Biliary obstruction, resection of ileum, chronic intestinal ischemia
• Malabsorption – Short bowel syndrome, Whipple’s disease,
celiac disease, tropical sprue, bacterial overgrowth, abetalipoproteinemia, GI lymphoma, glucose-galactose malabsorption, congenital chloridorrhea, hypogammaglobulinemia, parasitic infections
– Osmotically active dietary products: Psyllium fiber, magnesium citrate, sorbitol
• Altered motility
– increased peristalsis reduces transit time down GI tract
– Irritable bowel syndrome, hyperthyroidism, fecal impaction, neurologic diseases, diabetes, hypocalcemia, systemic sclerosis, GI bleeding, post-vagotomy
• Increased filtration
– GI capillary hydrostatic/oncotic pressure imbalance
– Portal hypertension, severe hypoalbuminemia, partial small bowel obstruction
• Iatrogenic – Medical treatment side effect
– GI surgery, Abdominal radiation therapy, medications (magnesium citrate, laxatives, antibiotics, cardiac medications, chemotherapeutic drugs, metoclopramide, cisapride, lactulose,theophyllin, etc.
• Factitious
– Self- induced
– Surreptitious laxative abuse associated with psychiatric disorders
Consistency • Formed
• Watery stool • Mucoidal
Constipation:
• Scybala: passage of small firm, spherical masses of stool
• Irritable colon syndrome secondary to anxiety or overuse of laxatives
• Carcinoma
• Repeated occult blood determination Narrow, ribbon-like stool:
• Spastic bowel or rectal narrowing or stricture
Color
• Clay colored stool:
– Diminution or absence of bile – Presence of barium sulfate
• Bloody stool:
– Red color stool Lower GIT Bleeding
Red Beets in the diet (false positive)
– Black tarry stool (melena)
Upper GIT Bleeding
Bismuth Iron and Charcoal intake (false positive)
• Green stool: – Biliverdin – Ingestion of spinach or green vegetables or
caramel (false positive) – Oral antibiotics (false positive)
Mucus
Recognizable mucus in stool is abnormal
• Transluscent gelatinous mucus on the surface of formed stool
– spastic constipation – mucous colitis
• Bloody mucus on stool – rectal neoplasm – inflammatory process in the rectal canal
• Mucus with pus and blood
– ulcerative colitis
– bacillary dysentery
– ulcerating diverticulitis
– intestinal TB
• Copius mucus (3 to 4 L/24hr)
– villous adenoma of the colon
Microscopic Examination
Pus
• Chronic ulcerative colitis
• Chronic bacillary dysentery
• Localized abcesses or fistulas communicating with
sigmoid colon, rectum, or anus
Fat
Method
• Sudan III • Sudan IV
• Oil Red O stains
Procedure
Neutral fat + soaps Fatty acids (stains strongly with Sudan III)
Indication
• Steatorrhea (Pancreatic origin)
Normal • 60-100/hpf of stained neutral fats)
Mineral oil or castor oil may mimic neutral fats
36% acetic acid
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Meat Fiber
Method
Stool + 10% alcohol sol’n of eosin Rectangular fibers with striations
Leukocytes
• Small fleck of mucus/ a drop of liquid stool • 2 gtts Loeffler methylene blue
• Average number of WBC and RBC/ hpf
Fleck of mucus/ + 2 gtt of Loeffler Nuclear staining 1 gtt of liquid stool Methylene blue (Leucocytes)
• Only cells (mononuclear or polymorphonuclear leukocytes are included)
• Average number of WBC and RBC/ hpf
Fecal Blood
Causes
• Hemorrhoids or anal fissures
• Drugs: – Salicylates, steroids, rauwolfia derivatives,
phenylbutazone, indomethacin • Tarry stool for 2-3 days: blood loss of at least 1000 ml
and occult blood may persist for 5 to 12 days
Occult Blood Tests: • Principle:
determination of peroxidase and pseudoperoxidase activity of RBCs including Hgb
indicator used
- Quaiac rgt, orthotoluidine, orthodinisidine, benzidine
• Procedure: (guaiac test)
Blood + H2O2 + (guaiac rgt) blue quinone (stool) cpd
• Normally: 2.0 to 2.5 mL blood loss in GIT
(+) occult blood test - blood loss of > 5-10 ml per day (5-10 mg of
hgb/gm stool)
• Food giving false positive results: myoglobin and hemoglobin from meat and
fish
aspirin-containing preparations and iron cpds.
bacteria in the intestines, veggies and fruits: horseradish, turnips, bananas, black grapes, pears, plums
• Drugs giving false positive results: Vit. C and other antioxidants
• HemoQuant Converts heme to fluorescent porphyrin Not affected by: dietary peroxidase, Vit. C,
specimen storage, or hydration
• Immunologic tests using antisera or human hgb: RID, ELISA, Latex agglutination, and
hemagglutination
Latex agglutination assays (rotavirus, adenovirus)
• High sensitivity
• High specificity
• High PPV
• High NPV
• A good alternative to electron microscopy
• Requirements for occult blood test: Diet free of exogenous sources of
peroxidase activity for at least 3 days before the test
High residue foods in the diet: prunes, bran, raw veggies, corn, and peanuts
• Should be done at LEAST 3X and preferably 6X
Carcinoid Tumors and the Carcinoid Syndrome
Carcinoid tumors
• Neuroendocrine neoplasms of entrerochromaffin cells belonging to the amine precursor uptake and decarboxylation(APUCD) system.
• Organs involved with argentaffin cells: appendix, terminal ileum, rectum, bronchus, jejenum, duodenum, stomach, liver, pancreas, and gonads
• Sxs: mechanical bowel obstruction or paraneoplastic manifestations with peak incidence in the 6th decade of life
Carcinoid syndrome
• Symptoms: • Skin flushing
• Abdominal cramps
• Nausea
• Vomiting
• Diarrhea
• Hypotension
• Bronchoconstriction • Cyanosis
• Cardiac lesions with endocardial and valvular thickening and fibrosis, predominantly involving the right ventricle
• Carcinoid tumors sythesize and release serotonin • Other hormones secreted:
gastrin ACTH
insulin glucagon
somatostatin hCG subunits
motilin calcitonin
Enterochromaffin cell (carcinoid tumors) ↓
Serotonin ↓
Tryptophan 5-HTP
Dopa decarboxylase Monoamine oxidase
5-HTP (5-hydroxytryptophan)
5-HT (5-hydroxytryptamine [serotonin])
5-HIAA (5-hydroxyindoleacetic acid) metabolite from 24-hour urine
3 mins
1-2 mins
tryptophan hydroxylase
5-HT
5-HIAA
Aldehyde dehydrogenase
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Diagnostic Tests for Carcinoid Syndrome
5-HIAA in 24 hr urine:
(acidified with 10 ml 6N HCl to prevent oxidation)
• Method: Colorimetry Fluorometry Gas chromatography Radioimmunoassay
Fluorescence polarization immunoassay
High-pressure liquid chromatography(HPLC)
• NV: 2-8 mg/24 hr • False positive increase:
A. Food
bananas
plantains
tomatoes
eggplant
B. Drugs
Acetaminophen
Guanifenesin
• False positive decrease: A. Drugs
Reserpine Salicylates Monoamine oxidase inhibitors
Phenothiazines L-dopa
Serotonin (5-HT) in blood
• Blood in EDTA tube with ascorbic acid as preservative
• Whole blood or platelet-rich plasma
• Method: HPLC
• Ref. interval: WB serotonin: 50 to 200 ng/ml Platelet rich plasma: 125 to 500 ng/109 platelets
Malabsorption Syndromes
• Definition: – Result from impaired digestion or
assimilation of foodstuffs by the small bowel
• Common causes: (pancreatic diseases )
Chronic pancreatitis
Carcinoma of the pancreas
Cystic fibrosis of the pancreas
• Manifestations: Creatorrhea
- Undigested meat fibers in the feces
Steatorrhea
- An increase in fat - largely triglyceride (>5 grams of lipids (FA) in feces/24hrs)
Hepatic Maldigestion
• Interference with bile flow
– Loss of bile salts interference
• Fat emulsificaton • Diminishes surface area available
for lipolytic action
• Loss of bile salt activation by lipase • Cause
– Neoplasma obstructing the ampulla of Vater
• Results
– Hepatic steatorrhea – Pancreatic steatorrhea
Enteric Malabsorption
• Normal digestion but inadequate net assimilation of food stuffs resulting from:
– Competition by bacteria
– Altered bacterial flora • Causes
– Blind loop syndrome
– Diverticulosis – Obstruction of the lymph flow
• Whipple disease
• Lymphoma – Diseases affecting the bowel mucosa
• Amyloidosis • Inflammation following radiation
– Atrophy of small bowel due to wheat protein, gluten or gliadin-sensitivity in coeliac disease
– Vitamin B6 or B12 deficiency • Deficiencies of fat-soluble vitamins: A,D,E,& K
• Weight loss due to large caloric loss & nutritional deficiencies :
– Hypoprothrombinemia
– Glossitis
– Anemia
– Edema
– Ascites
– Osteomalacia
• Single foodstuff or vitamin or small group of substances deficiency:
– Lactose intolerance - lactase deficiency – Pernicious anemia - Vit. B12 deficiency
due to intrinsic factor deficiency
• Major Sign
– Steatorrhea
Excretion or presence of more than 5 gms of lipid
Differentiating Causes
Pancreatic vs. enteric malabsorption
• Cystic fibrosis of the pancreas
o Sweat electrolyte determination
Result: increase sweat chloride
o Trypsin activity Result: absence of trypsin in stool
Enteric malabsorption • D-xylose absorption test (25 g pentose sugar in water
taken orally)
• Result: < 3g excretion in urine over a 5- hr period
Celiac disease:
• Cellobiose-mannitol permeability test • Lactulose-mannitol test
• Patients with celiac disease underabsorb small molecules such as mannitol and absorb larger molecules such cellulose and lactalose
Intestinal Disaccharidase Deficiency
• Primary Disaccharide Deficiencies
– Sucrase-isomaltase deficiency
– Lactase deficiency
– Primary alactasia – Primary trehalase deficiency
pineapple kiwi fruit walnuts
hickory nuts pecans avocados
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• Secondary Disaccharide Deficiencies
(transient; involve more than one enzyme)
– Celiac disease – Tropical sprue – Acute viral gastroenteritis
– Drugs (neomycin,kanamycin, methotrexate)
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
o Protracted diarrhea, bloating and flatulence
Screening tests for disaccharidase deficiencies:
• Oral challenge of suspected disaccharides stool analysis - watery, acidic (<pH5.5)
• Clinitest tablet (reducing substances) ≥0.5 g/dL or more than 250 mg/dl (abnormal)
Normal: 250 mg/dL of feces
• Definitive Dx: mucosa of small intestinal biopsy showing low enzymatic activity
Glucose – Galactose Malabsorption • Hereditary (autosomal recessive traits) disorder of
active absorption of glucose and galactose from the small intestine
• Problem: Diarrhea
• Laboratory tests
– Glucose oxidase – Galactose oxidase – Chromatography
– OGTT (flat curve)
Protein-Losing Enteropathy
Causes: • Ménétrier’s disease
• Gastric cancer
• Chronic gastritis
• Benign or malignant tumors
• Crohn’s disease
• Celiac disease
• Tropical sprue
• Ulcerative colitis
• Intestinal lymphatic obstruction
• Graft-vs.-host disease of the intestine
• Whipple’s disease (bacterial overgrowth)
• Infectious enteritis