Gastrointestinal Tract

BACKGROUND READING: Saliva & salivary glands Salivary gland function tests Stomach Gastric secretion Gastro-intestinal peptides

Digestion of carbohydrates, proteins & lipids Gastrectomy and post-gastrectomy syndromes Pancreas Pancreatitis

Gastrointestinal Tract
TREATED TOPICS Gastric function and tests Zollinger-Ellison syndrome Peptic ulcer Pancreatitis & pancreatic function Absorptive function of the gut

Gastro-intestinal peptides

Gastrin see later Secretin see later Cholecystokinin (CCK) see later

Glucose-dependent insulinotrophic peptide (GIP) found in duodenum and jejunum and involved in the postprandial release of insulin

Gastro-intestinal peptides

Motilin: Found in duodenum and jejunum and responsible for intestinal motor activity Pancreatic polypeptide: Found in the pancreas; relaxes gall bladder and inhibits enzyme secretion from the pancreas

Gastro-intestinal peptides

Gut glucagon-like immunoreactivity; Found in the ileum and colon; increases small intestinal mucosal growth and slows transit Vasoactive intestinal peptide (VIP): Found in all areas; secretomotor, vasodilation and relaxation of smooth muscle.

Intestinal absorptive surface

Digestion and absorption: Absorptive surface of the gut

Digestion of carbohydrates

Digestion of starch occurs mainly in the intestinal lumen. Pancreatic amylase acts on starch producing maltose, maltotriose and -limit dextrins by acting on 1 4 glucosidic linkages. Further metabolism of these products at the brush border which has isomaltase (-limit dextrinase) and disaccharidases (for maltose, sucrose, lactose) produce monosaccharides.

Digestion of carbohydrates

Carbohydrate malabsorption can result from:

Generalised intestinal disease affecting absorption. Pancreatic disease causing amylase deficiency. Intestinal disaccharidase deficiency Defects of monosaccharide transport.

Digestion and absorption of proteins.1

Pepsin acts within the stomach. Trypsin and chymotrypsin act in the intestinal lumen. These are all endopeptidases. Pancreatic exopeptidases split off terminal amino acids from proteins and peptides.

Digestion and absorption of proteins.2

Proteins are digested to oligopeptides (2-6 amino acids long) and free amino acids. Oligopeptides are digested at the brush border or within the luminal cell cytoplasm to amino acids.

Absorption of amino-acids

There are active transport mechanisms for transport of amino acids across mucosal cells into circulation. There are active transport mechanisms for basic (cystine, lysine ornithine, arginine) acidic, neutral and -imino acids (proline, hydroxyproline).

Malabsorption of proteins can result from:

Generalised intestinal disease affecting absorption Pancreatic disease causing deficiency of pancreatic peptidases Specific transport defects e.g. cystinuria, Hartnup disease.

Digestion and absorption of lipids.1

Emulsification of lipids for digestion is achieved by intestinal motility and the detergent-like action of bile acids. Lipids are digested, solubilised and then absorbed. Dietary triglycerides (TGs) are partially hydrolysed to free fatty acids (FFA) and mono and diacylglycerides

Digestion and absorption of lipids....2

The diacylglycerides, monoacylglycerides, FFA, cholesterol, phospho-lipids and fat soluble vitamins are organised into micelles (solubilisation) for absorption mainly in the jejunum.

Digestion and absorption of lipids....3

Within the mucosal cells triglycerides are resynthesized and together with cholesterol, phospholipid and protein are organised into chylomicrons Chylomicrons pass into the intestinal lymphatics and then into the thoracic duct. Some TGs and other lipids are organised into VLDL within intestinal mucosal cells (exogenous VLDL).

Digestion and absorption of lipids....4

Some FFAs escape into the portal blood and get bound to albumin and are then taken to the liver.

Digestion and absorption of Triglycerides

Digestion and absorption of triglycerides

FA+ MGs

Abnormalities of lipid absorption can result from:

Generalised intestinal disease affecting absorption. Pancreatic disease causing lipase deficiency Decreased lipase activity due to high intestinal [H+] Deficiency of bile acids Abeta lipoproteinaemia

GASTRIC FUNCTION

The stomach

Histamine Cell and Parietal Cell

Ranitidine

Gastric acid inhibition of gastrin release

.
H2R

H cells

Histamine

Gastric acid secretion

(Flow of information )

Cephalic phase of gastric acid secretion Vagus parietal cells (direct) Vagus nerve gastrin producing cells gastrin histamine producing cells histamine H2 R-parietal cells

Gastric acid secretion

(Flow of information )

Gastric phase of gastric acid secretion Secretagogues (protein, products of protein digestion) parietal cells (direct)

Distension of stomach Low gastric acid G-cells H-cells pareital cells gastrin histamine

Histamine Cell and Parietal Cell

Ranitidine

The proton pump

Omeprazole:
Proton pump inhibitor

Cimetidine: Ranitidine: H2R antagonists

The pentagastrin test

Patient fasting Pass radio-opaque naso-gastric tube Aspirate: Resting juice Basal juice (60 min) Inject sub-cutan pentagastrin 6 g/kg bdy wt Aspirate: Post-pentagastrin secretion (4 x15 min)

Pentagastrin Test: Reference ranges

Resting juice: <50ml Basal juice: <5 mmol/h (HCl) Post-pentagastrin secretion (MAO/PAO) : < 45mmol/h : <35 mmol/h

Achlorhydria
Inability to secrete gastric acid so that the pH of gastric juice produced in response to the pentagastrin test 7 May be found in : Pernicious anaemia Gastric carcinoma

Acid output

: duodenal ulcer Zollinger-Ellison syndrome

: gastric ulcer gastric carcinoma The above observations are not sufficiently constant

Peptic ulcer
An ulcer in or adjacent to an acid producing area of the gut Causes: mucosal resistance (Cells + mucus) Acid + pepsin NB: effective management of PU leads to 50% reduction in acid output (pre: intra-treatment)

The insulin-hypoglycaemia test (Hollanders test)

Patient fasting Pass radio-opaque naso-gastric tube Aspirate: Resting juice Basal juice (60 min) Inject sub-cutan insulin 0.2 u/kg bdy wt Aspirate: Post-insulin secretion (8 x 15 min)

Blood glucose during Hollanders test

Fasting blood glucose measured before injection of insulin Blood glucose measured at 15, 30, 45 and 60 minutes after the injection of insulin

The insulin-hypoglycaemia test: Reference ranges

Hypoglycaemia: plasma glucose< 2.2 mmol/L in at least one of the blood specimens

[H+] > 20 mmol/L above basal Incomplete vagotomy

Output in any 4 consecutive 15 min specimens 10 mmol Incomplete vagotomy

Plasma gastrin

Reflects the rate of gastrin production by the pyloric antrum [Plasma gastrin] in the fasting state when gastric acidity is high [Plasma gastrin] after meals when gastric acidity is low

Plasma gastrin

In diseases causing hyperacidity (e.g. DU) [plasma gastrin] except in Zollinger-Ellison syndrome

In hypochlorhydria or achlorhydria (e.g. pernicious anaemia) [plasma gastrin] except in a situation where atrophic gastritis has destroyed gastrin producing cells

Zollinger-Ellison syndrome

0.1% of all patients with PUD Severe, multiple recurrent peptic ulcers Autonomous gastrin production : 60-65%, : 30-35% Excessive production of acid by the stomach Non- islet cell tumour of the pancreas May occur as part of the MEN syndromes (20%)

Zollinger-Ellison syndrome
60% of the gastrinomas are malignant with metastasis in local lymph nodes and liver Symptoms / signs: Abdominal pain & dyspepsia Chronic diarrhoea & malabsorption as a result of inactivation of pancreatic enzymes by H+

Zollinger-Ellison syndrome: Diagnosis:

resting and basal juice in the pentagastrin test Overnight aspiration (resting juice)> 1L containing 100 mmol/L HCl Diagnosis confirmed by finding [plasma gastrin] in the fasting patient (100->1000 pg/ml) BAO/MAO> 0.6

Acid Secretin Nutrients CCK-PZ

The stomach, duodenum and pancreas

Pancreatic enzymes:

Proteases: trypsin, chymotrypsin, carboxypeptidases Amylase Lipolytic enzymes: lipase and co-lipase

Acute pancreatitis
Acute inflammation of the pancreas Two forms: Oedematous: (mortality: 5-10%)

Haemorrhagic /(Necrotizing) with severe tissue necrosis: (mortality: 2050%)

Causes: (GET SMASHED)

Gallstones Ethanol Trauma Steroids Mumps Auto-immune Scorpion venom

Hyperlipidaemia hypothermia, hypercalcaemia ERCP and Emboli Drugs

Acute pancreatitis
Associations: + 50 years Biliary tract disease (e.g. cholelithiasis) Alcoholism On elimination of the causative factor, normal exocrine and endocrine functions are restored

Acute pancreatitis

Gall stones present in about 50% of all cases About 5% of patients with gall stones develop acute pancreatitis Vascular and infective causes also known 25% of all cases are not secondary to any known cause (idiopathic)

Complications of acute pancreatitis (early)

Shock Acute respiratory distress syndrome (ARDS) Renal failure Sepsis Disseminated intravascular coagulation (DIC)

Complications of acute pancreatitis (early)

Hypocalcaemia (lipolysis with release of FFAs, followed by saponification reactions with calcium salts) Please read about late complications

Plasma -amylase

Activity usually in acute pancreatitis Values > 5x the upper reference value (180 Somorgyi u) found in > 50% of cases and usually occurs on the 1st or 2nd day of illness Smaller increases in most acute abdominal conditions In acute pancreatitis plasma -amylase activity returns to normal within 3-5 days

Urine -amylase
Rises with plasma -amylase but offers no advantage over measurement of plasma amylase Limitations: Renal decompensation in the elderly Macroamylasaemia (presence of aggregates of -amylase with immunoglobulins in plasma which are unable to pass through the kidney filter)

Lipase and trypsin activities:

Levels of lipase and trypsin are increased in acute pancreatitis and in other conditions where plasma - amylase activity is increased They are more difficult to measure than amylase Serum lipase is more sensitive and specific for pancreatitis and may eventually replace amylase measurements Lipase is only slowly cleared from plasma so remains elevated for a longer period than plasma amylase

Methaem-albuminaemia: Index of severity of acute pancreatitis

Develops sometimes in acute pancreatitis: Proteolytic breakdown of haemoglobin Haem /methaem formed Haem metabolized to bilirubin Methaem combines with plasma albumin to form methaem-albumin Usually only a trace of methaem-albumin is detectable in the plasma of healthy individuals

Chronic pancreatitis
Persistence of pain or symptoms after acute episode Structural and functional impairment: Impairment of pancreatic exocrine function (e.g. release of lipase) Impairment of pancreatic endocrine function (e.g. release of insulin)

Pancreatic function:

Secretin, Cholecystokinin-Pancreozymin (Secretin-CCK-PZ) test (tubular test)

Patient fasting Passage of double calibre tube Aspiration of duodenal samples: 10 min preliminary sample 10min 10min basal/controls

Secretin Cholecystokinin-Pancreozymin (Secretin-CCK-PZ) test

Injection of secretin 1U/kg bdy wt slow I.V. 10 min 10 min 20 min 20 min duodenal aspirations

CCK-PZ I.V. or Caerulein decapeptide

10min 10min

Results of the Secretin, CCK-PZ test

Volume
Basal Secretin CCK-PZ
10 ml

pH
7.5

bicarbonate Enzymes
25 mmo/l 75-90 mmol/l 75-90 mmol/l + + ++

>2ml/kg 8 bdy wt >2ml/kg bdy wt 8

Chr pancreat Ca pancreas

60 mmol/l

Pancreatic function:

Research test (tubeless test)

BT-PABA /14 C-PABA test

BT-PABA Oral
14

C-PABA

Urine Urine 14 C-PABA PABA Chymotrypsin

14C-PABAu

PABAu BT-PABAo

Benzoyl tyrosyl paraamino benzoic acid test

14C-PABAo

Pancreatic function:

test

Triglyceride breath

(also radioactive and tubeless)

This is one example of tests that have been devised so as to overcome the difficulties and unpleasantness of collecting faeces over several days (read about faecal fat). Following digestion and absorption of an oral dose of 14C-triglyceride the (marker being in the fatty acid component) part of the fatty acid is metabolised to 14CO2 which is then excreted in the expired air.

Triglyceride breath test

A high 14CO2 excretion is associated with normal fat absorption whereas 14CO excretion is low in patients with 2 fat malabsorption. This test is convenient and rapid but because it is technically difficult it has not gained wide acceptance.

Xylose absorption test1 Screening test for carbohydrate malabsorption 550052

D-xylose, a pentose is normally absorbed rapidly from the small intestine and excreted in the urine. It is partly metabolised in the body but can be used satisfactorily to test the intestines ability to absorb monosaccharides (remember that all
carbohydrates are absorbed as monosaccharides)

Xylose absorption test2

D-xylose (5g) is given to the patient after an overnight fast. The bladder is immediately emptied and this first specimen of urine discarded. Urine is collected for the next 5h. At least 500 ml water is given during the early part of the test. Normally in healthy individuals, more than 2g xylose is excreted in 5h.

Xylose absorption test3

Impaired absorption and excretion of xylose is often observed in patients with disease of the small intestine (read
on Crohns, Whipples, Tropical sprue, Gluten/gliadin enteropathy)

Bacterial colonisation of the small intestine may lead to low values because the bacteria metabolise xylose.

Xylose absorption test4

In renal disease there may be impaired excretion of xylose. Blood xylose measurements may be made for individuals with impaired renal function. In patients over 50 yrs, due to progressive loss of renal function with age, xylose excretion may be low in the absence of intestinal malabsorption.

Xylose absorption test5

The test can be used to monitor the response to therapy e.g. coeliac disease (gluten/gliadin enteropathy), tropical sprue syndrome.

Oral glucose tolerance test as a test of intestinal absorption

This test may help to differentiate pancreatic from other causes of malabsorption. Malabsorption caused by chronic pancreatitis is often found to have a diabetic type response whereas a flat response is more common in other forms of malabsorption

Glucose Tolerance Test

Disaccharide tolerance

Disaccharidase deficiency manifests as intolerance to one or more of the disaccharides; lactose, maltose or sucrose. Commonest: lactase def It may be congenital or acquired. NB: intestinal lactase activity declines with age

Disaccharide tolerance tests1

Determine whether there is an impairment of absorption of ingested disaccharides Help define whether any impairment is due to intestinal disaccharidase deficiency.

Disaccharide tolerance tests2

There is an overnight fast. A blood specimen for [glucose] is taken 50g disaccharide (lactose, sucrose or maltose) is given orally. Plasma glucose is measured at 30 minute intervals for the next 2 hours.

Disaccharide tolerance tests3

In healthy individuals plasma [glucose] should increase by as much as 1.1mmol/L (in at least one of the specimens). In disaccharidase deficiency / impairment of absorption the rise is usually less than 1.1mmol/L.

Disaccharide tolerance tests4

To eliminate the possibility that generalised mucosal disease is present, the test should be repeated using a mixture containing 25g of each of the monosaccharides that together make up the dissacharide.

Disaccharide tolerance tests5

Bacterial metabolism of unabsorbed disaccharide may lead to a faecal pH of less than 5.5. The most direct way of specifically diagnosing small intestinal disaccharidase deficiency is by peroral biopsy of intestinal mucosa and the measurement of disaccharidase activity.

Protein losing enteropathy.1

Intestinal protein loss is usually detected by the parenteral administration of radio-isotopically labelled macromolecules such as 125I, or 131I-labelled proteins or labelled polyvinyl pyrrolidone.

Protein losing enteropathy.2

Faecal radioactive iodine is then measured. Alternatively, faecal radioactivity can be measured following in vivo labelling of plasma proteins with 51Cr