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CHAPTER-3: GASTROINTESTINAL FUNCTIONAL TESTS

Acute Pancreatitis: An acute episode of enzymatic destruction of the pancreatic substance

due to the escape of active pancreatic enzymes into the pancreatic tissue.

Breath Tests: Tests that detect products of bacterial metabolism in the gut or products of

human metabolism by measuring, most commonly, CO2and H2 in the breath.

Celiac Disease (Gluten-Sensitive Enteropathy): A disease caused by the destructive

interaction of gluten with the intestinal mucosa causing malabsorption. In most cases, the

mucosal damage is reversed by withdrawing all gluten containing foods from the diet.

Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and

also found in the central nervous system. It causes gallbladder contraction and release of

pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions.

Chronic Pancreatitis: An inflammatory disease characterized by persistent and

progressive destruction of the pancreas.

Chyme: Food which has been acted upon by the churning action of the stomach and by

stomach juices, but has not yet been passed on into the intestine.

Crohn Disease: A chronic inflammatory disease that may affect any part of the intestine

from the mouth to the anus.

Cystic fibrosis (CF): An inherited disease caused by genetic alteration of a

transmembrane conductance regulator protein (CFTR) that leads to chronic pancreatic

and obstructive pulmonary disease. Cystic fibrosis affects many types of exocrine glands-

particular1y the sweat glands

(the sodium and chloride content of sweat is elevated)-hut also glands in the lung and

pancreas, causing the secretion of a viscous mucus liable, in the lung, to become infected.

Diarrhea: The passage of loose or liquid stools more than 3 times daily and/or a stool

weight greater than 200 g/day.

Digestion: The conversion of food, in the stomach and intestines, into soluble and

diffusible products, capable of being absorbed.

Digestive Process: A three-phase process-neurogenic, gastric, and intestinal. The

neurogenic (vagal) phase is initiated by the sight, smell, and taste of food. The gastric

phase is initiated by the distention of the stomach by the entry of food. The intestinal

phase begins when the partly digested food enters the duodenum from the stomach.

Dumping Syndrome: Following gastric surgery, hyperasmolar chyme is "dumped" into the

small intestine causing rapid hypovolemia and hemoconcentration.

Gastrin: A group of peptide hormones secreted by gastrointestinal mucosa cells of some

mammals in response to mechanical stress or high pH, both of which are produced by

the presence of food in the stomach. Gastrin stimulates the stomach parietal cells to

produce hydrochloric acid.

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*Gastrinoma: A tumor of the pancreatic islet cells that results in an overproduction of

gastric acid, leading to fulminant ulceration of the esophagus, stomach, duodenum, and

jejunum. Gastrinomas may also occur in the stomach, duodenum, spleen, and regional

lymph nodes.

Gastritis: Mucosal inflammation of the stomach. Glucose-dependent Insulin tropic

Peptide (GIP, Gastric Inhibitory Polypeptide): A peptide hormone (42 amino acids) that

stimulates insulin release and inhibits the release of gastric acid and pepsin.

Helicobacter pylori: A bacterium found in the mucous layer of the stomach. All strains

secrete (1) proteins that cause inflammation of the mucosa and (2) the enzyme urease

that produces ammonia from urea; some strains produce toxins that injure the gastric

cells.

**Lactose Intolerance: A condition due to lactase deficiency leading to malabsorption of

lactose and causing symptoms of flatulence, abdominal discomfort, bloating, or diarrhea

after drinking milk or foods containing lactose.

Malabsorption: An abnormality in the absorption of nutrients.

Maldigestion: An abnormality of the digestive process due to dysfunction of the pancreas

or small intestine.

Peptic Ulcer Disease: The collective name given to duodenal and gastric ulceration.

Postgastrectomy Syndrome: A syndrome following surgery for peptic ulcer disease that

includes the dumping syndrome, diarrhea, maldigestion, weight loss, anemia, bone

disease, and gastric cancer.

Secretin: A peptide -C=O(NH)hormone of the gastrointestinal tract (27 amino acid

residues) found in the mucosal cells of the duodenum. It stimulates pancreatic, pepsin,

and bile secretion, and inhibits gastric acid secretion. Considerable homology with GIP,

vasoactive intestinal peptide, and Body of Stomach

mucus, and intrinsic factor Sphincter glucagon.

Steatorrhea: A condition of excessive fat in feces (>5 g/day, >18 mmol/day).

Ulcerative Colitis: Recurrent inflammatory disease of the large bowel that always involves

the rectum and spreads to involve a variable amount of colon. Ulcerative colitis, like

Crohn disease, is a form of inflammatory bowel disease.

Vasoactive Intestinal Peptide (VIP): A peptide of 28 amino acids found in the central and

peripheral nervous system where it acts as a neurotransmitter. It is located in the enteric

nerves in the gut. It relaxes smooth muscle in the gut and increases water and electrolyte

secretion from the gut.

Zollinger-Ellison (Z-E) Syndrome: A condition resulting from a gastrin-producing tumor

(gastrinoma) of the pancreatic islet cells that results in an overproduction of gastric acid,

leading to ulceration of the esophagus, stomach, duodenum, and jejunum and causing

hypergastrinemia, diarrhea, and steatorrhea.

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Efficient digestion of food and absorption of nutrients are the result of coordinated

functions that occur in the gastrointestinal (GI) tract. Coordination and regulation of

these functions depend on hormones that stimulate or inhibit secretion of fluids

containing hydrochloric acid (XI), bile acids, bicarbonate, and digestive enzymes.

BASIC PRINCIPLES: ANATOMY

The GI tract is a 10-meter-long tube beginning with the mouth and ending with the anus.

The esophagus is about 25 cm in length and is a muscular tube connecting the pharynx

to the stomach. The major organs of the GI tract include the (1) stomach,

(2) small and large intestines,

(3) pancreas, and

(4) gallbladder, all of which are involved in the digestive processes that commence with

the ingestion of food and water and culminate in the excretion of feces.

Stomach 1. The stomach consists of three major zones: the cardiac zone, the body, and the

pyloric zone

(Figure 37-1).

2. The upper cardiac zone, which includes the fundus, contains mucus-secreting

surface epithelial cells and several types of endocrine secreting cells.

3. The body of the stomach contains cells of many different types, including mucus-

secreting cells and parietal (oxyntic) cells, which secrete HC1 and intrinsic factor.

Cells in all three zones of the stomach produce pepsinogens, the precursors of

the enzyme pepsin which degrades proteins in the food.

4. The pyloric zone is subdivided into the antrum (the distal third of the stomach),

the pylori canal, and the sphincter. The cells of the pyloric zone secrete mucus,

pepsinogens, serotonin, gastrin, and several other hormones but no HCI.

Small Intestine Food is converted in the stomach into a homogeneous, gruel-like material (chyme) that

passes through the pyloric sphincter into the small intestine, which consists of three parts:

the duodenum, jejunum, and ileum. In the adult human, the small intestine is

approximately 2 to 3 m long and decreases in cross-section as it proceeds distally. The

duodenum (about 25 cm long) is the shortest and widest part of the small intestine. The

jejunum and ileum make up the remainder of the small intestine.

Large Intestine The large intestine is approximately 1.5 m long and includes the cecum, appendix, colon,

rectum, and anal canal.

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GASTRIC FUNCTION

Gastric mucosa has different types of cells:

• Surface epithelial cells: secrete mucus

• Parietal cells: Secrete HCl (pH 0.8)and Intrinsic factor

• Chief cells: secrete Pepsinogen

• Entero-chromaffin cells: secrete Serotinin

• G-cells: secrete Gastrin [ stimulates secretion of HCl, Pepsinogen,

Intrinsic factor, Secretin, Pancreatic enzymes, HCO3- & Bile.

Increases Gastric & Intestinal motility, Increases mucosal growth]

• Other endocrine-secreting cells

• Total Gastric secretion about 2000ml

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HCl secretion

• Neurogenic phase of digestion starts with sight, smell and taste of

food stimulate Cereberal cortex stimulate Vagal nuclei Acetyl

choline secretion from Post ganglionic parasympathetic nerve

endings stimulation of parietal cells & G-cells secretion of HCl &

Pepsinogen

• HCl is secreted by Parietal cells under stimulation by Acetyl choline

(neurocrine), Histamine (paracrine) and Gastrin (endocrine pathway).

• H+ secretion into lumen is against 1 million fold Conc. gradient &

requires H+ / K+ ATPase

[pH of ECF= 7.4, pH of Gastric juice= 2 ]

• Histamine H2 receptor antagonists are used to inhibit acid secretion.

Eg. Cimetidine, Ranitidine, Famotidine: they block morphological

transformation of Parietal cells preceeding acid secretion.

• Omeprazole is taken up by Parietal cells & inactivates H+/ K+

ATPase. Synthesis of new enzyme takes 24 hrs.

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• Gastric phase of Digestion begins with distension of Stomach with

food: it stimulates secretion of Gastrin & HCl. Gastin stimulates

gastric motility & secretion of HCl, Pepsinogen, Pancreatic enzymes,

GI hormones (Secretin, Insulin, Somatostatin, Pancreatic

polypeptide). Neutralization of existing HCl by food also stimulates

HCl secretion.

• Food mixes with gastric secretion and is partly degraded to become

Chyme, which moves to Duodenum.

• Inside Parietal cells:

• CO2 + H2O carbonic anhydrase H2CO3

• H2CO3carbonic anhydrase H+ + HCO3-

• 1 K+ from Gastric lumen is exchanged for 1 H+ from Parietal cell

using 1 ATP

• 1 HCO3- from Parietal cell is exchanged for 1 Cl- from plasma.

• This causes ‘Alkaline tide’ in plasma and urine after meals.

• Cl- absorbed into Parietal cell is secreted into Gastric lumen.

:HCl Role of

Denaturation of proteins; optimum pH for digestive enzymes; Activation of

**Pepsin by partial proteolysis; Absorption of Calcium & Iron.

Gastric function tests write

Fractional test meal 1.

• Fasting stomach contents are aspirated and Gastric secretion is

stimulated using test meals (Porridge/ rice gruel/ black coffee/ toast).

• Timed samples of Gastric secretion are collected and analyzed for

free and total acidity: It is obsolete!

Pentagastrin stimulation test:2.

• Fasting stomach content is aspirated: Residual secretion.

• After 1 hr again stomach content is aspirated: Basal secretion

• Pentagastrin (gastrin analogue: -COOH-Butyl-Oxy- Ala-Trp-Met- Asp-

Phe -NH2) given 6mg/Kg body weight.

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• Gastric secretion is collected every 15 min for next hour.

• Basal acid output (BAO): Acid (in mmol/hr) in Basal secretion

• Maximal acid output (MAO): Sum of all acid (in mmol/hr) secreted

over one hour after Pentagastrin.

• Peak acid output (PAO): Twice [the sum of acid output in 2

consecutive samples having highest acid content]

Interpretation

1. Zollinger Ellison Syndrome: Gastrin secreting tumor in Pancreas. No

feedback regulation of Gastrin secretion. There is very high Gastric

acid + High serum Gastrin. BAO>15mmol/L, BAO/PAO ≥ 0.6

2. Chronic duodenal ulcer: BAO, MAO, PAO are very high.

3. BAO 4-6 mmol/ L, BAO/PAO ratio >0.3

Estimation of Free & Total Acidity

• Fasting contents are aspirated from stomach.

• Test meal is given.

• Gastric juice is aspirated after every ½ hr for 2 hrs.

• Free & Total acidity is measured in each sample by titration against

N/10 NaOH.

• Free acidity measures only HCl.

(Indicator Topfer’s: pKa= 3.5 or, Methyl Orange)

• Total acidity measures HCl + Other Organic acids.

(Indicator Phenopthalein: pKa= 10.5)

Augmented Histamine test

• Histamine (0.04mg/ Kg body weight) is given Subcutaneously to

stimulate acid secretion.

Interpretation

• If no acid secretion: True Hypoacidity (Pernicious anaemia)**

• If Hypoacidity patient has acid secretion in response to Histamine:

False Hypoacidity****

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• Histamine H1 receptor blocker Antihistamine is given prior to

Histamine to prevent Hypotension.

• Stomach has H2 receptors: blocked by Cimetidine: cure for Peptic

ulcers.

Tubeless Gastric Analysis • No need for Ryele’s tube.

• Used as Screening test.

• Gastric acid secretion stimulated by Histalogue.

• After 1 hr, Dye bound Resin (Azure A) is given orally.

• In presence of HCl, resin releases dye proportional to acidity.

• Released dye is absorbed from stomach and excreted in urine.

• Dye conc in urine indicates presence/ absence of HCl.

Causes of Hyperacidity

1. Duodenal ulcer

2. Gastric cell hyperplasia

3. Carcinoid tumour

4. ZE syndrome

5. Multiple endocrine neoplasia

6. Excessive Histamine production as in Systemic Mastocytosis

Causes of Hypoacidity

1. Gastritis

2. Gastric carcinoma

3. Partial gastrectomy

4. Pernicious anemia

Other Gastric Function Tests

• Serum Gastrin (by RIA) Normal<10 pmol/L (Never>50pmol/L)

ZE Syndrome [Zollinger-Ellison Syndrome (Gastrinoma)] >100 pmol/L

• Occult blood in Gastric juice: Gastric Ca, Gastric ulcer, Duodenal

ulcer

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• Bile/ undigested food in Gastric juice: Stagnation of food/

Regurgitation of bile

• Urease enzyme in Gastric biopsy: Helicobacter pylorii

• Bacteria produce NH3 by its Urease enzyme & escapes acid attack.

• It’s a cause of Acid peptic disease.

**********