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8 - Gastrointestinal and Exocrine Pancreatic Function

Glucagon

Glycogenolysis
Gluconeogenesis

Glucose
Glucose

Beta
Cells
Delta
Cells

Preinsulin
Insulin
Gastrin

Glucose uptake

Glucose

Digestion

Gastric acid

Exocrine Functions from the Acinar Cells


Cell
Production Enzymes
Acinar
Cells

Enzymes
and
proteolytic
enzymes
precursors

Trypsin
-Amylase
Cholesterol
esterase
Phospholipase A
Lipase

Digestive
Stimulation
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

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

Pancreatic
hyperamylasemia
Salivary
hyperamylasemia
Macroamylasemia
type 1
Macroamylasemia
type 2
Macroamylasemia

SERUM
AMACROAMYLASE

Alpha
Cells

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

Cam:Ccr

Endocrine Functions from the Islets of Langerhans


Cell
Production
Action
Outcome

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

URINARY
AMYLASE

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

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

SERUM
AMYLASE
SERUM
LIPASE

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

/N

/N

/N

Very

/N

N - Normal
M - Moderate
T - Trace
Cam:Ccr = amylase clearance:creatinine clearance ratio =
(urinary amylase/serum amylase) X (serum creatinine/urinary
creatinine)

rainwater@mymelody.com || 1st semester, AY 2011-2012

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

rainwater@mymelody.com || 1st semester, AY 2011-2012

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
Decreased para-aminobenzoic acid
Hydrolysis Test
results suggest pancreatic insufficiency
Fecal Fat
Values 5-10g% suggest malabsorption
Values > 10 g% suggest maldigestion
14C-Triolein
Decreased 14CO2 in expired air suggsts
Breath
fat malabsorption
D-Xylose
Values below reference ranges suggest
Absorption
little to no absorption capacity of the
proximal small bowel mucosa
Vitamin B12
Patients who excrete < 7% are
Malabsorption
suspected to have pernicious anemia
-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

Crohns 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
rainwater@mymelody.com || 1st semester, AY 2011-2012

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, Whipples 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

Color

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

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

36% acetic acid

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

Narrow, ribbon-like stool:


Spastic bowel or rectal narrowing or stricture

rainwater@mymelody.com || 1st semester, AY 2011-2012

Latex agglutination assays


(rotavirus, adenovirus)
High sensitivity

High specificity

High PPV
High NPV

A good alternative to electron


microscopy

Meat Fiber
Method
3 mins
Stool + 10% alcohol soln 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


1-2 mins

Fleck of mucus/ + 2 gtt of Loeffler


1 gtt of liquid stool Methylene blue

Nuclear staining
(Leucocytes)

Only cells (mononuclear or polymorphonuclear


leukocytes are included)
Average number of WBC and RBC/ hpf

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

Fecal Blood

Carcinoid Tumors and the Carcinoid Syndrome

Causes

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


th
manifestations with peak incidence in the 6 decade
of life

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

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 hydroxylase
Tryptophan
5-HTP
Dopa decarboxylase
Monoamine oxidase
5-HT
Aldehyde
dehydrogenase

5-HIAA

5-HTP (5-hydroxytryptophan)
5-HT (5-hydroxytryptamine [serotonin])
5-HIAA (5-hydroxyindoleacetic acid) metabolite from 24-hour
urine

rainwater@mymelody.com || 1st semester, AY 2011-2012

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
pineapple
hickory nuts
plantains kiwi fruit

pecans

tomatoes walnuts
avocados

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


9
Platelet rich plasma: 125 to 500 ng/10 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

rainwater@mymelody.com || 1st semester, AY 2011-2012

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:

Mntriers disease
Gastric cancer
Chronic gastritis
Benign or malignant tumors
Crohns disease
Celiac disease
Tropical sprue
Ulcerative colitis
Intestinal lymphatic obstruction
Graft-vs.-host disease of the intestine
Whipples disease (bacterial overgrowth)
Infectious enteritis

rainwater@mymelody.com || 1st semester, AY 2011-2012